Analysis Tools|
Allele Symbol Allele Name Allele ID |
Kras+ wild type MGI:1857552 |
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| Summary |
308 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a reduced life span, with an average half-life of 62 weeks
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: mean age at death is ~350 days on pure 129/Sv background compared to 300 days on mixed background
(J:68981)
• average lifespan is 373 days
(J:68981)
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• mice develop adenocarcinomas, adenomas, lymphomas, mesotheliomas, angiosarcomas, fibrosarcomas, squamous carcinomas, rectal mucinous adenocarcinomas, melanomas, and papillomas
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• Background Sensitivity: ~10% of animals develop thymic lymphoma; incidence is lower than on pure 129/Sv background
|
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• develop lung adenocarcinomas by 6-8 months of age
• treatment of mice with PX-866, a PI3K inhibitor, decreases lung lesion volume and multiplicity
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• 4 of 48 mice develop mesothelioma with no occurrence of peritoneal mesothelioma
|
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• Background Sensitivity: about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background
|
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• Background Sensitivity: about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background
|
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• develop lung adenocarcinomas by 6-8 months of age
• treatment of mice with PX-866, a PI3K inhibitor, decreases lung lesion volume and multiplicity
|
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• a subset of mutant terminal bronchi contain 4 to 7 bronchioalveolar stem cells (BASCs) compared to 3 of fewer in wild-type bronchi, indicating expansion of BASCs
|
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• Background Sensitivity: ~10% of animals develop thymic lymphoma; incidence is lower than on pure 129/Sv background
|
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• Background Sensitivity: ~10% of animals develop thymic lymphoma; incidence is lower than on pure 129/Sv background
|
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• Background Sensitivity: ~10% of animals develop thymic lymphoma; incidence is lower than on pure 129/Sv background
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:136369 , J:68981 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: mean age at death is ~300 days
|
|
• all animals at time of death/sacrifice have extensive tumor burden
|
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• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~20% of animals)
|
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• Background Sensitivity: animals are prone to skin papillomas (seen in ~25% of animals); tumors typically arising on ears and snout are predominantly pedunculated and show limited tendency to progress to squamous cell carcinoma
|
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• 100% of animals show multifocal tumors at time of death/sacrifice
• tumors are detectable at 1 week of age as small pleural nodules; multiplicity and size of tumors increases with age, and ultimately result in respiratory distress and death
• tumors range from mild hyperplasia/dysplasia to overt carcinoma; small lesions consist of hyperplastic alveolar epithelium
• in older mice, infrequent metastases to thoracic lymph nodes, the kidney and other visceral organs
|
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• as lesions enlarge, they form small alveolar adenomas; some show areas of glandular differentiation
|
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• 5-10% of tumors have features of well-differentiated human papillary adenocarcinoma
|
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• mutants have multiple aberrant crypt foci (ACF) of the colon
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• mutants have multiple aberrant crypt foci (ACF) of the colon
|
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• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~20% of animals)
|
|
• Background Sensitivity: animals are prone to skin papillomas (seen in ~25% of animals); tumors typically arising on ears and snout are predominantly pedunculated and show limited tendency to progress to squamous cell carcinoma
|
|
• 100% of animals show multifocal tumors at time of death/sacrifice
• tumors are detectable at 1 week of age as small pleural nodules; multiplicity and size of tumors increases with age, and ultimately result in respiratory distress and death
• tumors range from mild hyperplasia/dysplasia to overt carcinoma; small lesions consist of hyperplastic alveolar epithelium
• in older mice, infrequent metastases to thoracic lymph nodes, the kidney and other visceral organs
|
|
• as lesions enlarge, they form small alveolar adenomas; some show areas of glandular differentiation
|
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• 5-10% of tumors have features of well-differentiated human papillary adenocarcinoma
|
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• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~20% of animals)
|
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• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~20% of animals)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:68981 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: mean age at death is ~250 days on pure 129/Sv background compared to 200 days on mixed background
|
|
• Background Sensitivity: ~30% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background
|
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• Background Sensitivity: about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background
|
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• 100% of mice examined at 3-4 months of age have developed lung tumors
|
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• Background Sensitivity: about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background
|
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• Background Sensitivity: ~30% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background
|
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• 100% of mice examined at 3-4 months of age have developed lung tumors
|
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• Background Sensitivity: ~30% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background
|
|
• Background Sensitivity: ~30% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:68981 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• treatment with adenoviral Cre to induce oncogenic Kras expression results in lung tumor development, but causes a lower tumor burden and decreased overall tumor area compared to induced mutants on a Spry2-null background
(J:119477)
• 20% and 100% of mice develop lung lesions at 6 weeks and 20 weeks, respectively, post intranasal adenoviral cre administration
(J:216266)
• all mice delivered with an adenovirus expressing cre recombinase through nasal inhalation at 8 weeks of age develop lung tumors
(J:299900)
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• mice develop lung adenomas with a few adenocarcinomas following intratracheal administration of an adenovirus expressing Cre (Ad-Cre)
(J:207982)
• treatment with MLN4924, a small molecular inhibitor of NAE, beginning at 13 weeks after Ad-Cre administration reduces tumor burden, with a reduction in both number of hyperplastic areas and adenomas and size of the tumors
(J:207982)
• mice intratracheally administered an adenovirus expressing cre recombinase (Ad-cre) develop multiple lung adenomas
(J:333347)
|
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• a few adenocarcinomas develop in mice following Ad-Cre administration
(J:207982)
• mice intratracheally administered Ad-cre develop a few adenocarcinomas
(J:333347)
|
|
• treatment with adenoviral Cre to induce oncogenic Kras expression results in lung tumor development, but causes a lower tumor burden and decreased overall tumor area compared to induced mutants on a Spry2-null background
(J:119477)
• 20% and 100% of mice develop lung lesions at 6 weeks and 20 weeks, respectively, post intranasal adenoviral cre administration
(J:216266)
• all mice delivered with an adenovirus expressing cre recombinase through nasal inhalation at 8 weeks of age develop lung tumors
(J:299900)
|
|
• mice develop lung adenomas with a few adenocarcinomas following intratracheal administration of an adenovirus expressing Cre (Ad-Cre)
(J:207982)
• treatment with MLN4924, a small molecular inhibitor of NAE, beginning at 13 weeks after Ad-Cre administration reduces tumor burden, with a reduction in both number of hyperplastic areas and adenomas and size of the tumors
(J:207982)
• mice intratracheally administered an adenovirus expressing cre recombinase (Ad-cre) develop multiple lung adenomas
(J:333347)
|
|
• a few adenocarcinomas develop in mice following Ad-Cre administration
(J:207982)
• mice intratracheally administered Ad-cre develop a few adenocarcinomas
(J:333347)
|
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• mice intratracheally administered Ad-cre have a median survival time of approximately 130 days with 100% death by 175 days
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:207982 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: mean age at death is ~200 days
|
|
• all animals at time of death/sacrifice have extensive tumor burden
• mice display a more rapid tumor phenotype than Krastm2Tyj heterozygotes
|
|
• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~40% of animals)
|
|
• Background Sensitivity: animals are prone to skin papillomas (seen in ~20% of animals); tumors typically arising on ears and snout are predominantly pedunculated and show limited tendency to progress to squamous cell carcinoma
|
|
• 100% of animals show multifocal tumors at time of death/sacrifice
• tumors are detectable at 1 week of age as small pleural nodules; multiplicity and size of tumors increases with age, and ultimately result in respiratory distress and death
• tumors range from mild hyperplasia/dysplasia to overt carcinoma; small lesions consist of hyperplastic alveolar epithelium
• in older mice, infrequent metastases to thoracic lymph nodes, the kidney and other visceral organs
|
|
• as lesions enlarge, they form small alveolar adenomas; some show areas of glandular differentiation
|
|
• 5-10% of tumors have features of well-differentiated human papillary adenocarcinoma
|
|
• mutants have multiple aberrant crypt foci (ACF) of the colon
|
|
• mutants have multiple aberrant crypt foci (ACF) of the colon
|
|
• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~40% of animals)
|
|
• Background Sensitivity: animals are prone to skin papillomas (seen in ~20% of animals); tumors typically arising on ears and snout are predominantly pedunculated and show limited tendency to progress to squamous cell carcinoma
|
|
• 100% of animals show multifocal tumors at time of death/sacrifice
• tumors are detectable at 1 week of age as small pleural nodules; multiplicity and size of tumors increases with age, and ultimately result in respiratory distress and death
• tumors range from mild hyperplasia/dysplasia to overt carcinoma; small lesions consist of hyperplastic alveolar epithelium
• in older mice, infrequent metastases to thoracic lymph nodes, the kidney and other visceral organs
|
|
• as lesions enlarge, they form small alveolar adenomas; some show areas of glandular differentiation
|
|
• 5-10% of tumors have features of well-differentiated human papillary adenocarcinoma
|
|
• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~40% of animals)
|
|
• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~40% of animals)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:68981 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• heterozygotes are viable, fertile and display no behavioral deficits or spontaneous tumor formation up to 20 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no viable embryos are found after E11.5
|
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• at E9.5 mutant embryos display cardiomegaly
|
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• mutant embryos are small
|
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• neuroepithelial sections have extensive areas of architectural distortion and apoptosis
|
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• at E9.5 mutant embryos display cardiomegaly
|
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• mutant embryos are small
|
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• neuroepithelial sections have extensive areas of apoptosis
|
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• neuroepithelial sections have extensive areas of architectural distortion and apoptosis
|
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• at E9.5 mutant embryos display abnormal brain development
|
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• neuroepithelial sections have extensive areas of apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase have a median survival of 79 days
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop noninvasive adenoma and adenocarcinoma over a 6-10 week period, characterized by epithelial cell proliferation without destruction of alveolar walls or stromal reaction
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop noninvasive adenoma and adenocarcinoma over a 6-10 week period, characterized by epithelial cell proliferation without destruction of alveolar walls or stromal reaction
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop noninvasive adenoma and adenocarcinoma over a 6-10 week period, characterized by epithelial cell proliferation without destruction of alveolar walls or stromal reaction
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop noninvasive adenoma and adenocarcinoma over a 6-10 week period, characterized by epithelial cell proliferation without destruction of alveolar walls or stromal reaction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tumor induction via intratracheal injection of Ad-Cre virus, lung tumors exhibit significantly higher protein levels of ZNF768 (zinc finger protein 768) than normal lung tissue, as quantified by ZNF768 immunochemistry staining using the H-score
|
|
• following intratracheal injection of Ad-Cre virus, mice develop lung tumor lesions ranging from atypical adenomatous hyperplasia (AAH) to adenocarcinomas
|
|
• following intratracheal injection of Ad-Cre virus, mice develop lung tumor lesions ranging from atypical adenomatous hyperplasia (AAH) to adenocarcinomas
|
|
• following intratracheal injection of Ad-Cre virus, mice develop lung tumor lesions ranging from atypical adenomatous hyperplasia (AAH) to adenocarcinomas
|
|
• following intratracheal injection of Ad-Cre virus, mice develop lung tumor lesions ranging from atypical adenomatous hyperplasia (AAH) to adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• after ovarian intrabursal injection of an adenovirus expressing Cre, mutants develop benign ovarian endometriosis-like lesions, however no invasive ovarian tumors are seen up to 10 months following adenoviral injection
|
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• 47% of mutants develop peritoneal endometriosis following ovarian intrabursal injection of an adenovirus expressing Cre
• however, mice injected with adenovirus expressing Cre directly into the peritoneum do not develop peritoneal endometriosis
|
|
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• after ovarian intrabursal injection of an adenovirus expressing Cre, mutants develop benign ovarian endometriosis-like lesions, however no invasive ovarian tumors are seen up to 10 months following adenoviral injection
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| endometriosis | DOID:289 | J:96296 | ||
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% survival at 40 weeks of age following intratracheal instillation of Ad-Cre
|
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• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), 50% of mice die by 40 weeks
|
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• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre)
|
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• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:172200 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median life span of cre adenovirus-treated mice is 32 weeks
|
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• tumors from cre adenovirus-treated mice exhibit increased cell proliferation compared to in tumors from Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
|
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• cre adenovirus-treated mice develop smaller tumors than in cre adenovirus-treated Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
|
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• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
(J:147590)
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas and bronchiolar hyperplasia and dysplasia
(J:147590)
• cre adenovirus-treated mice develop fewer tumors than in Krastm4Tyj/Kras+ Rb1tm3Tyj/Rb1tm3Tyj mice
(J:147590)
• large tumors easily visible on the surface of the lungs at eight weeks after Cre-adenovirus treatment
(J:158937)
|
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• presence of atypical adenomatous hyperplasia after Cre-adenovirus treatment
|
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• the most common lesion is adenocarcinoma after Cre-adenovirus treatment
|
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• in cre adenovirus-treated mice
|
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• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
(J:147590)
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas and bronchiolar hyperplasia and dysplasia
(J:147590)
• cre adenovirus-treated mice develop fewer tumors than in Krastm4Tyj/Kras+ Rb1tm3Tyj/Rb1tm3Tyj mice
(J:147590)
• large tumors easily visible on the surface of the lungs at eight weeks after Cre-adenovirus treatment
(J:158937)
|
|
• presence of atypical adenomatous hyperplasia after Cre-adenovirus treatment
|
|
• the most common lesion is adenocarcinoma after Cre-adenovirus treatment
|
|
• in cre adenovirus-treated mice
|
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• in cre adenovirus-treated mice
|
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• cre adenovirus-treated mice develop bronchiolar hyperplasia and dysplasia unlike wild-type mice
|
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• in cre adenovirus-treated mice
|
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• presence of epithelial hyperplasia after Cre-adenovirus treatment
|
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• following injection of a cre adenovirus in the ovarian bursa, mice with endometriosis also exhibit an increase in spleen and regional lymph nodes T regulatory cells compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
|
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• following injection of a cre adenovirus in the ovarian bursa, mice with endometriosis also exhibit an increase in spleen and regional lymph nodes T regulatory cells compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
|
|
|
• following injection of a cre adenovirus in the ovarian bursa, mice develop ovarian lesions consisting of endometrial glandular epithelium unlike un-injected Krastm4Tyj micefollowing injection of a cre adenovirus in the ovarian bursa, mice develop ovarian lesions consisting of endometrial glandular epithelium unlike un-injected Krastm4Tyj mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lung adenocarcinomas cover 11% of lung area 9 weeks after administration of a Cre-recombinase expressing adenovirus
|
|
• lung adenocarcinomas cover 11% of lung area 9 weeks after administration of a Cre-recombinase expressing adenovirus
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:203686 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following administration of a flp-expressing adenovirus or lentivirus
|
|
• following administration of a flp-expressing adenovirus or lentivirus
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:172206 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a median survival of 24 weeks after ad-cre inoculation
|
|
• mice inoculated with ad-cre by inhalation develop lung tumors with high multiplicity, long latency, and low aggressiveness
• all tumors of ad-cre inoculated mice are adenocarincomas
• metastasis or local invasion is not seen in ad-cre inoculated mice
|
|
• mice inoculated with ad-cre by inhalation develop lung tumors with high multiplicity, long latency, and low aggressiveness
• all tumors of ad-cre inoculated mice are adenocarincomas
• metastasis or local invasion is not seen in ad-cre inoculated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice are indistinguishable from wild-type mice and show no alterations of the thyroid gland
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% of mice die within 7 weeks from birth and none survive over 4 months of age
• treatment with LY294002, an inhibitor of PI3K, twice a week starting at 3 weeks of age prolongs survival of mice
|
|
• mice develop thyroids 200- to 500-fold larger than controls
|
|
• mice rapidly develop thyroid follicular carcinomas
• 30-90% of the thyroid glands are replaced by microfollicular to solid areas, indicating thyroid follicular cancer, including capsular, muscle, and vascular invasion
|
|
• mice rapidly develop thyroid follicular carcinomas
• 30-90% of the thyroid glands are replaced by microfollicular to solid areas, indicating thyroid follicular cancer, including capsular, muscle, and vascular invasion
|
|
• all mice surviving at least 12 weeks develop thyroglobulin-positive lung metastases
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreatic tumors exhibit higher proliferation rates than in Krastm4Tyj Ptf1atm1.1(cre)Cvw heterozygotes
|
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• in 8 of 10 mice at 26 weeks
|
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• at 6 weeks of age
|
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• at 34 weeks of age, 4 of 10 mice develop metastasis to the lung and liver compared to 6 of 10 metastasis at 48 weeks in Krastm4Tyj Ptf1atm1.1(cre)Cvw heterozygotes
|
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• pancreatic weight is greater than in Krastm4Tyj Ptf1atm1.1(cre)Cvw heterozygotes
|
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• pancreatic tumors exhibit higher proliferation rates than in Krastm4Tyj Ptf1atm1.1(cre)Cvw heterozygotes
|
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• in 8 of 10 mice at 26 weeks
|
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• at 6 weeks of age
|
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• pancreatic weight is greater than in Krastm4Tyj Ptf1atm1.1(cre)Cvw heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase have a median survival of 43 days
|
|
• tumors of Cre adenoviral treated mutants show transmural invasion of vessels and pleural invasion, and regional metastases to mediastinal lymph nodes
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop tumors similar to human mixed subtype adenocarcinomas; they show progression of a pure noninvasive lung adenocarcinoma to an adenocarcinoma with mixed invasive morphology and metastatic potential
• tumors of mutants treated with Cre adenovirus show evidence of inflammatory cell recruitment and tumor microenvironment remodeling with neoangiogenesis not seen in homozygous cre adenovirus treated Krastm4Tyj mice
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in B cells in the lungs compared to homozygous cre adenovirus treated Krastm4Tyj mice
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in T cells in the lungs compared to homozygous cre adenovirus treated Krastm4Tyj mice
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit a lower myeloid cell population in the lungs than controls
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in B cells in the lungs compared to homozygous cre adenovirus treated Krastm4Tyj mice
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit and increase in T cells in the lungs compared to homozygous cre adenovirus treated Krastm4Tyj mice
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase exhibit a lower myeloid cell population in the lungs than controls
|
|
• mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop tumors similar to human mixed subtype adenocarcinomas; they show progression of a pure noninvasive lung adenocarcinoma to an adenocarcinoma with mixed invasive morphology and metastatic potential
• tumors of mutants treated with Cre adenovirus show evidence of inflammatory cell recruitment and tumor microenvironment remodeling with neoangiogenesis not seen in homozygous cre adenovirus treated Krastm4Tyj mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:177379 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following tumor induction via intratracheal injection of Ad-Cre virus, both low- and high-grade adenocarcinomas exhibit significantly higher protein levels of ZNF768 (zinc finger protein 768) than normal lung tissue, as quantified by ZNF768 immunochemistry staining using the H-score
• notably, ZNF768 protein levels are positively correlated with tumor grade, with high-grade adenocarcinomas exhibiting even higher protein levels than low-grade ones
|
|
• following intratracheal injection of Ad-Cre virus, mice develop lung tumor lesions ranging from atypical adenomatous hyperplasia (AAH) to low- and high-grade adenocarcinomas
|
|
• following intratracheal injection of Ad-Cre virus, mice develop lung tumor lesions ranging from atypical adenomatous hyperplasia (AAH) to low- and high-grade adenocarcinomas
|
|
• following intratracheal injection of Ad-Cre virus, mice develop lung tumor lesions ranging from atypical adenomatous hyperplasia (AAH) to low- and high-grade adenocarcinomas
|
|
• following intratracheal injection of Ad-Cre virus, mice develop lung tumor lesions ranging from atypical adenomatous hyperplasia (AAH) to low- and high-grade adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice
|
|
• following adenovirus cre infection, mice exhibit impaired DNA damage response compared with control mice
|
|
• following adenovirus cre infection, mice exhibit impaired DNA damage response compared with control mice
|
|
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreatic tumors exhibit lower proliferation rates than in Krastm4Tyj Ptf1atm1.1(cre)Cvw Tg(MUC1)79.24Gend heterozygotes
(J:138959)
• mice exhibit carcinoma in situ in the pancreas
(J:234412)
|
|
• in 1 of 10 mice at 26 weeks
|
|
• mice exhibit high-grade PanIN lesions and carcinoma in situ, associated with disorganized glandular epithelium
(J:234412)
• mice treated with gemcitabine exhibit normal pancreatic glandular structure 26 weeks after the beginning of treatment
(J:234412)
|
|
• at 48 weeks, 6 of 10 mice develop metastasis to the lung and liver compared to 4 of 10 metastasis at 34 weeks of age in Krastm4Tyj Ptf1atm1.1(cre)Cvw Tg(MUC1)79.24Gend heterozygotes
|
|
• pancreatic tumors exhibit lower proliferation rates than in Krastm4Tyj Ptf1atm1.1(cre)Cvw Tg(MUC1)79.24Gend heterozygotes
(J:138959)
• mice exhibit carcinoma in situ in the pancreas
(J:234412)
|
|
• in 1 of 10 mice at 26 weeks
|
|
• mice exhibit high-grade PanIN lesions and carcinoma in situ, associated with disorganized glandular epithelium
(J:234412)
• mice treated with gemcitabine exhibit normal pancreatic glandular structure 26 weeks after the beginning of treatment
(J:234412)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| adenoma | DOID:657 | J:138959 | ||
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:234412 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with 4-hydroxytamoxifen (4-OHT) neonatally exhibit the presence of nevi and hyperpigmented regions on the paws and tails
|
|
• mice treated with 4-OHT neonatally develop melanoma with 76% penetrance and a median latency of 36.3 weeks
• melanomas contain both spindle-cell and desmoplastic cell types with no overt signs of macrometastatic spread
|
|
• mice treated with 4-OHT neonatally develop melanoma with 76% penetrance and a median latency of 36.3 weeks
• melanomas contain both spindle-cell and desmoplastic cell types with no overt signs of macrometastatic spread
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| skin melanoma | DOID:8923 | J:220627 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 36% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are carcinomas
|
|
• 20% of mutants injected with an adenovirus expressing cre recombinase in the distal colon to inactivate Apc exhibit spontaneous gross liver metastases starting 24 weeks after adenoviral injection; these lesions are adenocarcinomas
|
|
• 96% of mutants injected with an adenovirus expressing cre recombinase in the distal colon to inactivate Apc develop distal colonic tumors as little as 3 weeks after viral administration
• rapamycin treatment of mutants with tumors does not result in tumor regression
|
|
• 64% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are adenomas
|
|
• 64% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are adenomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:156532 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop pancreatic cancer
|
|
• all pancreata of 7-month old mice are replaced by aggressive pancreatic ductal adenocarcinoma with lung and liver metastasis
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring pancreatic adenocarcinoma
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
|
|
• average survival is 5.2 +/- 1.2 months
|
|
• mice develop pancreatic cancer
|
|
• all pancreata of 7-month old mice are replaced by aggressive pancreatic ductal adenocarcinoma with lung and liver metastasis
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring pancreatic adenocarcinoma
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring PanI
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:289183 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• 73.3% of 3-month old and 75% of 12-month old mice show normal pancreas
• although 26.7% of 3-month old and 25% of 12-month old mice show rare acinar-ductal metaplasia and low-grade pancreatic intraepithelial neoplasia (PanIN1) lesions, these lesions express TRIM29 due to incomplete recombination of the floxed allele
|
| N |
• all mice are alive at 12 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• primary pancreatic acinar cells from 1.5-month-old mice grown in 3D collagen culture undergo acinar-ductal metaplasia, forming large duct-like structures, indicating induction of acinar-to-ductal transdifferentiation
|
|
• mice with cerulein-induced acute pancreatitis do not show reversion of acinar-ductal metaplasia lesions to normal acinar morphology as in wild-type mice and show complete replacement of pancreatic tissue with fibrosis, infiltration of inflammatory cells, widespread acinar-ductal metaplasia/ pancreatic intraepithelial neoplasia (PanIN) lesions with loss of amylase-expressing acinar tissue, and maintain a small and persistent fraction of apoptotic cells
|
|
• mice with cerulein-induced acute pancreatitis do not show reversion of acinar-ductal metaplasia lesions to normal acinar morphology as in wild-type mice and show complete replacement of pancreatic tissue with fibrosis, infiltration of inflammatory cells, widespread acinar-ductal metaplasia/ pancreatic intraepithelial neoplasia (PanIN) lesions with loss of amylase-expressing acinar tissue, and maintain a small and persistent fraction of apoptotic cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice with cerulein-induced acute pancreatitis show reversion of acinar-ductal metaplasia lesions to normal acinar morphology after 7 days of recovery as in wild-type mice
|
|
• primary pancreatic acinar cells from 1.5-month-old mice grown in 3D collagen culture show attenuated KRAStm4Tyj-induced acinar cell transdifferentiation and acinar-ductal metaplasia formation
|
|
• primary pancreatic acinar cells from 1.5-month-old mice grown in 3D collagen culture show attenuated KRAStm4Tyj-induced acinar cell transdifferentiation and acinar-ductal metaplasia formation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average survival is 8.5 +/- 2.3 months
|
|
• initiation and progression of acinar-ductal metaplasia and pancreatic intraepithelial neoplasia (PanIN) lesions are slower than in Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53+ Gt(ROSA)26Sortm1(EYFP)Cos/Gt(ROSA)26Sor+ (KPCY) mice
• mice show lower pancreatic ductal adenocarcinoma and metastasis incidence than in KPCY mice
|
|
• mice show lower lung and liver metastasis from pancreatic ductal adenocarcinoma than in KPCY mice
|
|
• initiation and progression of acinar-ductal metaplasia and pancreatic intraepithelial neoplasia (PanIN) lesions are slower than in Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53+ Gt(ROSA)26Sortm1(EYFP)Cos/Gt(ROSA)26Sor+ (KPCY) mice
• mice show lower pancreatic ductal adenocarcinoma and metastasis incidence than in KPCY mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 13.1 weeks
• 25% of tumors exhibit sarcomatoid carcinoma histology
|
|
• 75% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
|
• 25% of tumors exhibit metastasis
|
|
• mutants develop pancreatic tumors with an average latency of 13.1 weeks
• 25% of tumors exhibit sarcomatoid carcinoma histology
|
|
• 75% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:108298 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 18.3 weeks
• 100% of tumors are sarcomatoid in histology
|
|
• 33% of tumors exhibit metastasis
|
|
• mutants develop pancreatic tumors with an average latency of 18.3 weeks
• 100% of tumors are sarcomatoid in histology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 21.8 weeks
|
|
• 100% of tumors are well differentiated ductal adenocarcinomas
|
|
• 33% of tumors exhibit metastasis
|
|
• mutants develop pancreatic tumors with an average latency of 21.8 weeks
|
|
• 100% of tumors are well differentiated ductal adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 7.2 weeks
• 60% of tumors exhibit anaplastic carcinoma histology
|
|
• 40% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
|
• 20% of tumors exhibit metastasis
|
|
• mutants develop pancreatic tumors with an average latency of 7.2 weeks
• 60% of tumors exhibit anaplastic carcinoma histology
|
|
• 40% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:108298 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 6.5 weeks
• 20% of tumors exhibit anaplastic carcinoma histology
|
|
• 80% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
|
• mutants develop pancreatic tumors with an average latency of 6.5 weeks
• 20% of tumors exhibit anaplastic carcinoma histology
|
|
• 80% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:108298 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 6.2 weeks
|
|
• mutants exhibit rapid pancreatic ductal adenocaracinoma progression, developing lethal tumors by 8 weeks of age
• 100% of tumors are well differentiated ductal adenocarcinomas
|
|
• mutants develop pancreatic tumors with an average latency of 6.2 weeks
|
|
• mutants exhibit rapid pancreatic ductal adenocaracinoma progression, developing lethal tumors by 8 weeks of age
• 100% of tumors are well differentiated ductal adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:108298 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 14.7 weeks
• 19% of tumors exhibit sarcomatoid differentiation
|
|
• 81% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
|
• 25% of tumors exhibit metastasis
|
|
• mutants develop pancreatic tumors with an average latency of 14.7 weeks
• 19% of tumors exhibit sarcomatoid differentiation
|
|
• 81% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• early mortality with a median survival of 8 weeks
|
|
• progressive phenotype characterized by cellular atypia, adenoma, and ultimately adenocarcinoma in CC10 positive cells of bronchial epithelia
|
|
• a robust inflammatory response characterized by an abundant infiltration of alveolar macrophages and neutrophils
|
|
• progressive phenotype characterized by cellular atypia, adenoma, and ultimately adenocarcinoma in CC10 positive cells of bronchial epithelia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a similar overall pancreatic tumor burden as KPCT (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor+) mice
• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice
• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells
• cancer cells exhibit a higher mitotic index than KPCT mice
|
|
• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice
|
|
• mice exhibit a shorter survival than KPCT mice
|
|
• mice exhibit a similar overall pancreatic tumor burden as KPCT (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor+) mice
• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice
• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells
• cancer cells exhibit a higher mitotic index than KPCT mice
|
|
• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• most mice develop metastases which are numerous and widespread in many different sites, including the lymph nodes, diaphragm, lungs, and liver
• all mice exhibit peritoneal disseminated tumor cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• seen in all mice
|
|
• mice die between 8 and 24 weeks of age
• average tumor-free survival is 15.7 weeks
|
|
• 12 of 12 mice develop intraductal papillary mucinous neoplasms
|
|
• 2 of 12 mice develop pancreatic ductal adenocarcinoma
|
|
• 2 of 12 mice develop pancreatic ductal adenocarcinoma
|
|
• seen in all mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 of 4 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
• tumor fibrosis is increased compared to mice wild-type for Smad4
|
|
• average tumor-free survival is 8.8 weeks
|
|
• 4 of 4 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
• tumor fibrosis is increased compared to mice wild-type for Smad4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 12 of 13 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
|
|
• average tumor-free survival is 14 weeks
|
|
• 5 of 13 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
|
|
• 12 of 13 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• number of induced tumors and total tumor area are significantly higher with Spry2 deficiency following treatment with adenoviral Cre
|
|
• number of induced tumors and total tumor area are significantly higher with Spry2 deficiency following treatment with adenoviral Cre
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation that is similar to that in single Kras mutants without further additive effects
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mice show 50% survival at 63 weeks compared to 38 weeks in single Kras heterozygous controls, indicating an 83% increase in survival
|
|
• tumor burden is reduced compared to single Kras heterozygotes; tumors that are found express Raf1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation compared to single Kras heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with tamoxifen at P10 develop liver tumors that are exclusively intrahepatic cholangiocarcinoma
|
|
• mice injected with tamoxifen at 8 weeks after birth develop multiple liver tumors that are all hepatocellular carcinoma and hepatocellular dysplasia, but not intrahepatic cholangiocarcinoma
|
|
• mice injected with tamoxifen at P10 develop liver tumors that are exclusively intrahepatic cholangiocarcinoma
|
|
• mice injected with tamoxifen at 8 weeks after birth develop multiple liver tumors that are all hepatocellular carcinoma and hepatocellular dysplasia, but not intrahepatic cholangiocarcinoma
|
|
• mice injected with tamoxifen at P10 develop liver tumors that are exclusively intrahepatic cholangiocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice
• however, tumorigenesis is the same as in Map2k7tm1.1Twad/Map2k7tm1.2Twad Krastm4Tyj/Kras+ mice
|
|
• following adenovirus cre infection, mice exhibit more adenocarcinomas than Map2k7tm1.1Twad/Map2k7tm1.2Twad Krastm4Tyj/Kras+ mice
|
|
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice
• however, tumorigenesis is the same as in Map2k7tm1.1Twad/Map2k7tm1.2Twad Krastm4Tyj/Kras+ mice
|
|
• following adenovirus cre infection, mice exhibit more adenocarcinomas than Map2k7tm1.1Twad/Map2k7tm1.2Twad Krastm4Tyj/Kras+ mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following cre-adenovirus treatment, all mice develop primary lung tumors
• following cre-adenovirus treatment, lung tumors resemble those found in Krastm4Tyj heterozygotes
• following cre-adenovirus treatment, tumors occupy 24% of lung space
|
|
• at 6 weeks following cre-adenovirus treatment, mice have lesions ranging from atypical adenomatous hyperplasia to small adenomas that are smaller than in Krastm4Tyj Trp53tm1Brn homozygotes
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors
• following cre-adenovirus treatment, lung tumors resemble those found in Krastm4Tyj heterozygotes
• following cre-adenovirus treatment, tumors occupy 24% of lung space
|
|
• at 6 weeks following cre-adenovirus treatment, mice have lesions ranging from atypical adenomatous hyperplasia to small adenomas that are smaller than in Krastm4Tyj Trp53tm1Brn homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• however, treatment with a potent and selective oral pan class I PI3K inhibitor (GDC 0941) blocks tumor growth
|
|
• however, treatment with a potent and selective oral pan class I PI3K inhibitor (GDC 0941) blocks tumor growth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival time of Ad-Cre treated mice is 37.9 weeks, with most mice dying by 60 weeks
|
|
• mice show reduced lung tumor burden following intratracheal administration of an adenovirus expressing Cre (Ad-Cre) compared to single Kras homozygotes, however the number of hyperplastic loci is not affected
• hyperplasia or adenomas from Ad-Cre treated mice show reduced proliferation compared to single Kras homozygotes
|
|
• mice show reduced lung tumor burden following intratracheal administration of an adenovirus expressing Cre (Ad-Cre) compared to single Kras homozygotes, however the number of hyperplastic loci is not affected
• hyperplasia or adenomas from Ad-Cre treated mice show reduced proliferation compared to single Kras homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival time of Ad-Cre treated mice is 27.6 weeks, with all mice dying by 33 weeks
|
|
• mice develop lung adenomas with a few adenocarcinomas following intratracheal administration of an adenovirus expressing Cre (Ad-Cre)
|
|
• a few adenocarcinomas develop in mice following Ad-Cre administration
|
|
• mice develop lung adenomas with a few adenocarcinomas following intratracheal administration of an adenovirus expressing Cre (Ad-Cre)
|
|
• a few adenocarcinomas develop in mice following Ad-Cre administration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 19 weeks following cre-adenovirus treatment, sinonasal adenocarninomas develop in 64% of mice
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the maximum survival is 24 days
|
|
• lung weight is 10-fold higher than that in control mice at 3 weeks old
|
|
• lung weight is 10-fold higher than that in control mice at 3 weeks old
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following cre-adenovirus treatment, a subset of tumors are highly invasive and grow into the hilus, heart, and overlying pleura
• following cre-adenovirus treatment, lymph node metastases are present in over 50% of mice
|
|
• at 19 weeks following cre-adenovirus treatment, sinonasal adenocarninomas develop in 14% of mice
|
|
• mice infected with low-titre (5X103) lentiviruses expressing Cre and Nfkbia have either a single lung adenocarcinoma or none at all
• mice infected with high-titre (5X104) lentiviruses expressing Cre and Nfkbia have 6-22 lung adenocarcinomas detected per mouse
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
|
|
• at 6 weeks following cre-adenovirus treatment, mice have lesions ranging from atypical adenomatous hyperplasia to small adenomas that are larger than in Krastm4Tyj Trp53tm1Brn heterozygotes
(J:103407)
• lung adenocarcinomas cover 11% of lung area 6 weeks after administration of a Cre-recombinase expressing adenovirus
(J:203686)
|
|
• following cre-adenovirus treatment, all mice develop advanced pulmonary adenocarinomas
(J:103407)
• following cre-adenovirus treatment, multiple tumors are present ranging from well-defined tumors to advanced highly dysplastic lesions containing large sheets of dysplastic cells, abnormal mitoses, and multinucleated giant cells
(J:103407)
• seventeen weeks after infection with low-titre (5X103) cre lentiviruses, an average of 30 lung adenocarcinomas are detected per mouse
(J:154041)
• seventeen weeks after infection with high-titre (5X104) cre lentiviruses, 90-131 lung adenocarcinomas are detected per mouse
(J:154041)
• mice develop multiple, aggressive adenocarcinomas in the lungs bilaterally following intranasal delivery of an adenovirus expressing Cre recombinase
(J:195492)
• tumor growth is reduced to a similar extent following either two 7.3 Gy fractions of radiation therapy or a single 11.6 Gy fraction
(J:195492)
• tumors incorporate high levels of BrdU 4 hours after radiation treatment similarly to unirradiated tumors, indicating lack of an intact G1 cell-cycle checkpoint
(J:195492)
|
|
• mice do not survive to 26 weeks post cre-adenovirus treatment in contrast to Krastm4Tyj Trp53tm1Brn heterozygous mice
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
|
|
• at 6 weeks following cre-adenovirus treatment, mice have lesions ranging from atypical adenomatous hyperplasia to small adenomas that are larger than in Krastm4Tyj Trp53tm1Brn heterozygotes
(J:103407)
• lung adenocarcinomas cover 11% of lung area 6 weeks after administration of a Cre-recombinase expressing adenovirus
(J:203686)
|
|
• following cre-adenovirus treatment, all mice develop advanced pulmonary adenocarinomas
(J:103407)
• following cre-adenovirus treatment, multiple tumors are present ranging from well-defined tumors to advanced highly dysplastic lesions containing large sheets of dysplastic cells, abnormal mitoses, and multinucleated giant cells
(J:103407)
• seventeen weeks after infection with low-titre (5X103) cre lentiviruses, an average of 30 lung adenocarcinomas are detected per mouse
(J:154041)
• seventeen weeks after infection with high-titre (5X104) cre lentiviruses, 90-131 lung adenocarcinomas are detected per mouse
(J:154041)
• mice develop multiple, aggressive adenocarcinomas in the lungs bilaterally following intranasal delivery of an adenovirus expressing Cre recombinase
(J:195492)
• tumor growth is reduced to a similar extent following either two 7.3 Gy fractions of radiation therapy or a single 11.6 Gy fraction
(J:195492)
• tumors incorporate high levels of BrdU 4 hours after radiation treatment similarly to unirradiated tumors, indicating lack of an intact G1 cell-cycle checkpoint
(J:195492)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:203686 , J:103407 , J:154041 , J:195492 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in Krastm4Tyj Ptf1atm1(cre)Hnak double heterozygotes
|
|
• as in Krastm4Tyj Ptf1atm1(cre)Hnak double heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice administered tamoxifen at 8 weeks of age show a median survival of 30 days after tamoxifen injection
|
|
• colonic serrated epithelial changes in tamoxifen treated mice
|
|
• hyperplastic changes of gastric mucosa in tamoxifen treated mice
|
|
• extrahepatic bile duct is rigid and dilated in tamoxifen treated mice
• papillary hyperplasia of the extrahepatic biliary tract
|
|
• papillary hyperplasia of the gallbladder in tamoxifen treated mice
|
|
• gallbladder and cystic duct are rigid and dilated in tamoxifen treated mice
|
|
• in tamoxifen treated mice
|
|
• PanIN-like lesions and hyperplasia in the pancreatic ducts in tamoxifen treated mice
• however, no obvious tumors are seen in mice administered tamoxifen at 8 weeks of age
|
|
• obstructive pneumonia in tamoxifen treated mice
|
|
• extrahepatic bile duct is rigid and dilated in tamoxifen treated mice
• papillary hyperplasia of the extrahepatic biliary tract
|
|
• papillary hyperplasia of the gallbladder in tamoxifen treated mice
|
|
• gallbladder and cystic duct are rigid and dilated in tamoxifen treated mice
|
|
• in tamoxifen treated mice
|
|
• liver of tamoxifen treated mice shows pre-malignant papillary ductal lesions in periportal areas
|
|
• PanIN-like lesions and hyperplasia in the pancreatic ducts in tamoxifen treated mice
• however, no obvious tumors are seen in mice administered tamoxifen at 8 weeks of age
|
|
• obstructive pneumonia in tamoxifen treated mice
|
|
• papillary hyperplasia of bronchial epithelia in tamoxifen treated mice
|
|
• respiratory failure by lung lesions in tamoxifen treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no macroscopic or microscopic skin tumors are observed up to 4 months after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice die within 2 months from intestinal cancers before developing skin tumors
|
|
• tamoxifen treated mice develop intestinal cancers
|
|
• tamoxifen treated mice develop intestinal cancers
|
|
• when back skin from mutant animals is grafted onto back skin of nude mice, all engrafted mice develop skin tumors, including ulcerative lesions (benign and squamous cell carcinomas) within 2 months of tamoxifen administration
|
|
• tamoxifen treated mice develop terminal intestinal carcinomas with 2 months of treatment
|
|
• when back skin from mutant animals is grafted onto back skin of nude mice, all engrafted mice develop skin tumors, including ulcerative lesions (benign and squamous cell carcinomas) within 2 months of tamoxifen administration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in mice lacking the BRF1 knock-in
|
|
• as in mice lacking the BRF1 knock-in
|
|
• tRNA levels are increased in the pancreas
|
|
• as in mice lacking the BRF1 knock-in
|
|
• tRNA levels are increased in the pancreas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as severe as in mice wild-type for Cd9
|
|
• at 8 weeks, more severe than in mice heterozygous for the Cd9 conditional allele
|
|
• at 8 weeks, more severe than in mice heterozygous for the Cd9 conditional allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
|
|
• at 8 weeks, not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
• increased tumor weight compared to in mice homozygous for a conditional allele
|
|
• compared to in mice homozygous for a conditional allele
|
|
• at 8 weeks, not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
• increased tumor weight compared to in mice homozygous for a conditional allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die by 30 weeks of age
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Cre-adenovirus treatment results in G2M cell-cycle arrest in embryonic fibroblasts
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median life span is 170 days
• longer median life span than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice (170 vs. 22 days)
|
|
• lung weight and histology are indistinguishable from littermate control mice at 3-week old, compare with lung weight is 10-fold higher in Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice
|
|
• lung weight and histology are indistinguishable from littermate control mice at 3-week old
• but eventually develop lung tumors at older age
|
|
• lung weight and histology are indistinguishable from littermate control mice at 3-week old
• but eventually develop lung tumors at older age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 76% fewer tumors and 79% smaller lesion area than Krastm4Tyj heterozygous mice after Cre-adenovirus treatment
|
|
• the lung surface of Cre-adenovirus treated mice is nearly indistinguishable from that of control mice
• 76% fewer tumors and 79% smaller lesion area than Krastm4Tyj heterozygous mice after Cre-adenovirus treatment
|
|
• presence of small adenomas after Cre-adenovirus treatment
|
|
• adenocarcinoma in 1 of 11 mice after Cre-adenovirus treatment
|
|
• the lung surface of Cre-adenovirus treated mice is nearly indistinguishable from that of control mice
• 76% fewer tumors and 79% smaller lesion area than Krastm4Tyj heterozygous mice after Cre-adenovirus treatment
|
|
• presence of small adenomas after Cre-adenovirus treatment
|
|
• adenocarcinoma in 1 of 11 mice after Cre-adenovirus treatment
|
|
• presence of epithelial hyperplasia after Cre-adenovirus treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• longer life span than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice (>100 days in some cases)
|
|
• lung weight is less than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice but higher than in normal mice
|
|
• lung weight is less than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice
|
|
• lung weight is less than Lyz2tm1(cre)Ifo, Krastm4Tyj heterozygous mice but higher than in normal mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when mice older than 6 weeks are given systemic tamoxifen treatment by intraperitoneal delivery, mice develop multiple tumors at clinically relevant sites with a median tumor free survival of 153 days (longer latency than Pax7CE mutants
|
|
• tamoxifen treated mice develop sarcomas that are exclusively undifferentiated pleomorphic sarcomas (UPS), myogenic or nonmyogenic in type
• tumors can appear in the body wall, the extremities, or the head and neck region
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• extremity sarcomas in mice injected with Ad-Cre invade adjacent skeletal muscle and uterine sarcomas invade the intestinal wall and pancreas
• 20% of mice with large extremity sarcomas develop metastasis to the lungs
|
|
• 90% of mice injected intramuscularly with an adenovirus expressing Cre recombinase (Ad-Cre) into the extremities develop soft tissue sarcomas after a median time of 3 months
(J:125101)
• high penetrance of soft tissue sarcomas also develops after injection of Ad-Cre into the uterus
(J:125101)
• soft tissue sarcomas present as large solitary masses originating at the site of Ad-Cre injection, and are high-grade spindle cell neoplasms
(J:125101)
• sarcomas show myofibroblastic differentiation with intracytoplasmic filaments with densities
(J:125101)
• gene expression analysis indicates that Ad-Cre induced sarcomas are undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma
(J:155389)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with flp-expressing adenovirus and tamoxifen on the same day exhibit sarcomas
• however, delayed tamoxifen-treatment reduces sarcoma formation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lung adenocarcinomas cover 11% of lung area 6 weeks after administration of a Cre-recombinase expressing adenovirus
• tumor burden progresses from 11% of lung (6 weeks) to 45% at experimental endpoint (12+ weeks) in the presence of a Cre-recombinase expressing adenovirus
• Mapkap2 expressing tumors (MK2+) represent a higher proportion of tumor burden, however over time the proportion of these tumors decreases and the proportion of Mapkapk2 (MK2-) null tumors increases in the presence of a Cre-recombinase expressing adenovirus
• proportion of total lung tumor burden composed of Mapkapk2 (MK2-) null tumors is reduced from 39% to 11% following cisplatin treatment
|
|
• lung adenocarcinomas cover 11% of lung area 6 weeks after administration of a Cre-recombinase expressing adenovirus
• tumor burden progresses from 11% of lung (6 weeks) to 45% at experimental endpoint (12+ weeks) in the presence of a Cre-recombinase expressing adenovirus
• Mapkap2 expressing tumors (MK2+) represent a higher proportion of tumor burden, however over time the proportion of these tumors decreases and the proportion of Mapkapk2 (MK2-) null tumors increases in the presence of a Cre-recombinase expressing adenovirus
• proportion of total lung tumor burden composed of Mapkapk2 (MK2-) null tumors is reduced from 39% to 11% following cisplatin treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in pIpC-treated mice similar to in pIpC-treated Krastm4Tyj Tg(Mx1-cre)1Cgn mice
|
|
• pIpC-treated mice develop myeloproliferative disorder with anemia unlike wild-type mice that is similar to in pIpC-treated Krastm4Tyj Tg(Mx1-cre)1Cgn mice
|
|
• bone marrow cells from pIpC-treated mice spontaneous form colony forming units-granulocyte and macrophage (CFU-GM) in the absence of cytokines unlike wild-type cells
|
|
• in pIpC-treated mice similar to in pIpC-treated Krastm4Tyj Tg(Mx1-cre)1Cgn mice
|
|
• pIpC-treated mice develop myeloproliferative disorder with anemia unlike wild-type mice that is similar to in pIpC-treated Krastm4Tyj Tg(Mx1-cre)1Cgn mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression
|
|
• mice develop liver tumors at 6 months of age, showing obvious symptoms after 7 months with abdominal distension due to multiple tumors at later stages
• mice develop liver tumors with both hepatocyte and cholangiocyte differentiation
|
|
• majority of large nodules are hepatocellular dysplasia, a precursor lesion of hepatocellular carcinoma
|
|
• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression
|
|
• mice develop liver tumors at 6 months of age, showing obvious symptoms after 7 months with abdominal distension due to multiple tumors at later stages
• mice develop liver tumors with both hepatocyte and cholangiocyte differentiation
|
|
• majority of large nodules are hepatocellular dysplasia, a precursor lesion of hepatocellular carcinoma
|
|
• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 46 days
|
|
• seen in 5 month old mice
|
|
• all mice start to show abdominal distension at about 5 weeks of age, frequently accompanied by jaundice and weight loss
• distension is due to hepatic enlargement and/or hemorrhagic ascites
|
|
• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma
• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen
• no metastasis or invasion to other organs is seen
• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens
• stellate cells are activated and acquire a myofibroblast-like phenotype
• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct
|
|
• multiple solid tumors with various sizes are seen throughout the liver
• invasive tumors are apparent after 7 weeks of age, with abundant desmoplastic stroma or desmoplasia
|
|
• various degrees of hyperplasia are seen in the bile ducts, characterized by increase in number and size and change in morphology, at 4 weeks of age
• at 5 weeks, a part of the hyperplastic ductal lesions at the hilum become enlarged and show a pattern of papillary growth
|
|
• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma
• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen
• no metastasis or invasion to other organs is seen
• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens
• stellate cells are activated and acquire a myofibroblast-like phenotype
• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct
|
|
• various degrees of hyperplasia are seen in the bile ducts, characterized by increase in number and size and change in morphology, at 4 weeks of age
• at 5 weeks, a part of the hyperplastic ductal lesions at the hilum become enlarged and show a pattern of papillary growth
|
|
• tumors primarily show glandular morphology that resembles well-differentiated human cholangiocarcinoma and marker analysis indicates that tumors are intrahepatic cholangiocarcinoma
• in some cases, regions of moderately differentiated tumor with a cribriform appearance are seen
• no metastasis or invasion to other organs is seen
• tumors are frequently surrounded by dense fibrous stroma, indicating accumulation of fibrillar collagens
• stellate cells are activated and acquire a myofibroblast-like phenotype
• tumor cells show mucin production, a characteristic of epithelial cells in the bile duct
|
|
• multiple solid tumors with various sizes are seen throughout the liver
• invasive tumors are apparent after 7 weeks of age, with abundant desmoplastic stroma or desmoplasia
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| intrahepatic cholangiocarcinoma | DOID:4928 | J:254370 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival is 52 weeks of age
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age
• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
|
• tumors are highly metastatic, with tumors showing invasion into adjacent organs such as the diaphragm, bowel, pancreas and stomach or distant metastasis to the lymph nodes, spleen, lungs, or peritoneal cavity
|
|
• intrahepatic cholangiocarcinoma is associated with biliary hamartomas
|
|
• hepatic lesions frequently show hemorrhage into the peritoneal cavity and exhibit evidence of tumor necrosis
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age
• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age
• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| intrahepatic cholangiocarcinoma | DOID:4928 | J:184949 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival is 19 weeks of age
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 9 weeks of age
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
|
• tumors are highly metastatic, with 75% of mutants having tumors showing invasion into adjacent organs such as the diaphragm, bowel, pancreas and stomach or distant metastasis to the lymph nodes, spleen, lungs, or peritoneal cavity
|
|
• intrahepatic cholangiocarcinoma is associated with biliary hamartomas
|
|
• hepatic lesions frequently show hemorrhage into the peritoneal cavity and exhibit evidence of tumor necrosis
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 9 weeks of age
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 9 weeks of age
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| intrahepatic cholangiocarcinoma | DOID:4928 | J:184949 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• many mice do not survive to 13 weeks after tamoxifen treatment due to high tumor burden
• mice display leaky cre expression without tamoxifen treatment and survive a few months longer than tamoxifen-treated animals
|
|
• after tamoxifen treatment, mice show a more severe phenotype than animals with wild-type Trp53 (greater tumor size, tumor growth and tumor grade); by 3-4 weeks after tamoxifen treatment, several small adenomas of papillary nature are observed in alveoli
• at 10 weeks after tamoxifen injection, many alveoli have large tumors; tumors exhibit enlarged pleomorphic nuclei, aberrant mitosis; tumor giant cells are present
|
|
• mice surviving to 13 weeks after tamoxifen treatment have adenocarcinomas in the alveoli of the lungs
• without tamoxifen treatment, mice develop invasive lung adenocarcinomas localized to the alveoli
• bronchioalveolar duct junctions (BADJs) appear normal ( in mice with or without tamoxifen treatment)
|
|
• after tamoxifen treatment, mice show a more severe phenotype than animals with wild-type Trp53 (greater tumor size, tumor growth and tumor grade); by 3-4 weeks after tamoxifen treatment, several small adenomas of papillary nature are observed in alveoli
• at 10 weeks after tamoxifen injection, many alveoli have large tumors; tumors exhibit enlarged pleomorphic nuclei, aberrant mitosis; tumor giant cells are present
|
|
• mice surviving to 13 weeks after tamoxifen treatment have adenocarcinomas in the alveoli of the lungs
• without tamoxifen treatment, mice develop invasive lung adenocarcinomas localized to the alveoli
• bronchioalveolar duct junctions (BADJs) appear normal ( in mice with or without tamoxifen treatment)
|
|
• 8 days after tamoxifen treatment, extensive type II cell proliferation is observed compared to wild-type; however, proliferating bronchioalveolar stem cells (BASCs) are rarely observed (at 8 days, 3, 6, 10 and 13 weeks after tamoxifen treatment)
• tumor cells express type II cell markers and are highly proliferative, even without tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice develop melanomas with spindle-like morphology
|
|
• 3 of 7 (43%) mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology at a median latency greater than 52 weeks compared with Cdkn2atm2.1Nesh/Cdkn2atm2.1Nesh Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53tm1Brn Tg(Tyr-cre/ERT2)13Bos mice whose median latency is 14 weeks
|
|
• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice
|
|
• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice treated with tamoxifen neonatally die within 14 weeks of treatment due to aggressive melanomas with spindle-like morphology unlike control mice in which only one mouse develops melanoma over a period of 60 weeks
|
|
• tumor growth is more aggressive than in Cdkn2atm1Rdp/Cdkn2atm1Rdp Tg(Tyr-HRAS)60Lc mice
|
|
• tamoxifen-treated mice develop melanomas with spindle-like morphology
|
|
• all mice treated with tamoxifen neonatally die within 14 weeks of treatment due to aggressive melanomas with spindle-like morphology unlike control mice in which only one mouse develops melanoma over a period of 60 weeks
• tumors in tamoxifen-treated mice occur on the flank, ear, and tail
• the number of tumors in tamoxifen-treated mice is greater than in similarly treated Cdkn2atm2.1Nesh/Cdkn2atm2.1Nesh Krastm4Tyj/Kras+ Tg(Tyr-cre/ERT2)13Bos mice or Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53tm1Brn Tg(Tyr-cre/ERT2)13Bos mice
• by 15 weeks, 17 of 27 adult mice treated with tamoxifen develop melanomas at the site of application and depilation
• however, no uveal tumors are observed
|
|
• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice
|
|
• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit rapid development of pancreatic tumors within 8 weeks with features typical of human pancreatic adenocarcinoma
• tumors treated with ibrutinib show a reduction in proliferation rate and tumor fibrosis, inhibition of mast cell degranulation, and reduction in CD11b+ and F4/80+ macrophages and mice show increased survival
• mice treated with both ibrutinib and gemcitabine show extended survival compared to treatment with gemcitabine alone
• mice treated with a daily injection of cromolyn, a blocker of mast cell degranulation and inflammogen release, starting at 8 weeks of age show a reduction in F4/80+ cells and CD11b+ cells in the tumor stroma
|
|
• mice exhibit rapid development of pancreatic tumors within 8 weeks with features typical of human pancreatic adenocarcinoma
• tumors treated with ibrutinib show a reduction in proliferation rate and tumor fibrosis, inhibition of mast cell degranulation, and reduction in CD11b+ and F4/80+ macrophages and mice show increased survival
• mice treated with both ibrutinib and gemcitabine show extended survival compared to treatment with gemcitabine alone
• mice treated with a daily injection of cromolyn, a blocker of mast cell degranulation and inflammogen release, starting at 8 weeks of age show a reduction in F4/80+ cells and CD11b+ cells in the tumor stroma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:220300 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• large, prominent goblet cells develop in the colon
|
|
• mice develop widespread hyperplasia throughout the colonic epithelium
• colonic epithelium has a larger transit amplifying cell zone than wild-type; cells in the colonic epithelium have a higher mitotic index than in wild-type
|
|
• hyperplasia is typified by extreme lengthening of the crypts
|
|
• hyperplasia is typified by extreme lengthening of the crypts
|
|
• large, prominent goblet cells develop in the colon
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a mean survival of 14 weeks after ad-cre inoculation
|
|
• 4 of 9 (44%) ad-cre inoculated mice exhibit metastasis
|
|
• mice inoculated ad-cre by inhalation develop lung adenocarcinomas with high multiplicity
|
|
• mice inoculated ad-cre by inhalation develop lung adenocarcinomas with high multiplicity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice do not survive beyond P21
|
|
• mice develop highly aggressive adenocarcinoma with a ductal cell phenotype and inflammation resembling human pancreatic ductal adenocarcinoma within a short period (5 and 10 days after birth) and die within 3 weeks
• at P16, pancreatic ductal adenocarcinoma progresses to occupy the whole pancreas and to invade the muscular wall of the duodenum
|
|
• PanIN-3 are detected in the pancreas with inflammation at P3 and P4
|
|
• mice develop highly aggressive adenocarcinoma with a ductal cell phenotype and inflammation resembling human pancreatic ductal adenocarcinoma within a short period (5 and 10 days after birth) and die within 3 weeks
• at P16, pancreatic ductal adenocarcinoma progresses to occupy the whole pancreas and to invade the muscular wall of the duodenum
|
|
• PanIN-3 are detected in the pancreas with inflammation at P3 and P4
|
|
• invasive features of pancreatic ductal adenocarcinoma are seen containing acinoductal metaplasia at P5-P10
|
|
• hemorrhagic ascites are seen by P16
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:214846 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced glutamate uptake and intracellular levels in organoids derived from tumor initiating cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lesions are squamous cell carcinomas (SCCs)characterized by fibroblast-like shaped cells and disruption of basal lamina
• numerous microscopic and small invasive SCCs are observed in the dermis of the back skin in addition to the macroscopic lesions
|
|
• within 2 months of tamoxifen treatment, animals develop rapidly growing ulcerative skin lesions in the back skin
|
|
• lesions are squamous cell carcinomas (SCCs)characterized by fibroblast-like shaped cells and disruption of basal lamina
• numerous microscopic and small invasive SCCs are observed in the dermis of the back skin in addition to the macroscopic lesions
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| squamous cell carcinoma | DOID:1749 | J:172048 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals have greatly reduced life-span compared to mutants expressing wild-type Kras
|
|
• adenocarcinomas show uniform high-grade dysplasia, including large, fused glands with serrated borders, pseudostratified epithelium, loss of apical-basal polarity, and high nucleus to cytoplasm ratio
• mice have more tumors than mutants expressing wild-type Kras
• terminally differentiated cells are absent from tumors
|
|
• adenocarcinomas show uniform high-grade dysplasia, including large, fused glands with serrated borders, pseudostratified epithelium, loss of apical-basal polarity, and high nucleus to cytoplasm ratio
• mice have more tumors than mutants expressing wild-type Kras
• terminally differentiated cells are absent from tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice develop melanomas with spindle-like morphology
|
|
• 5 of 11 mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology at a longer latency (median latency 31 weeks) than in Cdkn2atm2.1Nesh/Cdkn2atm2.1Nesh Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53tm1BrnTg(Tyr-cre/ERT2)13Bos mice (median latency 14 weeks)
|
|
• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice
|
|
• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 5 days in culture, pancreatic explants exhibit irregular branching and disorganization with increased proliferation, pseudostratification, nuclear crowding and elongation resembling precancerous lesions
• however, no cysts develop
|
|
• after 5 days in culture, pancreatic explants exhibit irregular branching with increased proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lungs at E12.5 show increased branching compared to Kras; Meox2-cre, Spry2-wild-type lungs; bronchi number is increased, but is still less than age-matched wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 18% of assessable tumor cases develop an acinar-cell carcinoma component of pancreatic tumors
|
|
• high penetrance (29 of 30 mutants) of pancreatic ductal adenocarcinomas
|
|
• average survival time is 84 days, with a range of 48-110 days
|
|
• about 18% of assessable tumor cases develop an acinar-cell carcinoma component of pancreatic tumors
|
|
• high penetrance (29 of 30 mutants) of pancreatic ductal adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:166678 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreatic insufficiency; spectrum of anomalies are seen from isolated paucity of the islets of Langerhans to complete fibro-inflammatory or cystic degeneration of both the endocrine and exocrine pancreas
|
|
• pancreata from 6 day old mutants exhibits an increase in apoptotic cells compared to controls
|
|
• pancreatic insufficiency; spectrum of anomalies are seen from isolated paucity of the islets of Langerhans to complete fibro-inflammatory or cystic degeneration of both the endocrine and exocrine pancreas
|
|
• mutants not succumbing to pancreatic insufficiency later develop pancreatic ductal adenocarcinomas with a moderate latency and incomplete penetrance (6 of 32 mutants)
|
|
• mutants exhibit shortened pancreatic ductal adenocarcinoma-free survival
|
|
• mutants not succumbing to pancreatic insufficiency later develop pancreatic ductal adenocarcinomas with a moderate latency and incomplete penetrance (6 of 32 mutants)
|
|
• pancreata from 6 day old mutants exhibits an increase in apoptotic cells compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 18 weeks after tamoxifen treatment, numerous adenomas develop in alveoli; small numbers of cells with features of malignant transformation are observed in some lung sections
• tumors are usually found in proximity to the airways, bronchioalveolar duct junctions (BADJs), or surface of the lung, but lesions are not found in the BADJs
• tumor cells are highly proliferative
• airways and BADJs retain normal architecture
|
|
• by 18 weeks after tamoxifen treatment, numerous adenomas develop in alveoli; small numbers of cells with features of malignant transformation are observed in some lung sections
• tumors are usually found in proximity to the airways, bronchioalveolar duct junctions (BADJs), or surface of the lung, but lesions are not found in the BADJs
• tumor cells are highly proliferative
• airways and BADJs retain normal architecture
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a decrease in median survival time which is approximately 4.5 months of age
|
|
• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs with only 2 mice showing liver metastasis
|
|
• both low and high grade PanIN lesions are seen at 2-3 months of age, but by 6 months, invasive carcinoma is present
|
|
• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs with only 2 mice showing liver metastasis
|
|
• both low and high grade PanIN lesions are seen at 2-3 months of age, but by 6 months, invasive carcinoma is present
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:248550 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a decrease in median survival time which is approximately 2 months of age
|
|
• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs
|
|
• mice develop classical PanIN lesions that progress to invasive carcinoma
|
|
• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs
|
|
• mice develop classical PanIN lesions that progress to invasive carcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:248550 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average tumor-free survival is 38 weeks
|
|
• 6 of 10 mice develop pancreatic ductal adenocarcinoma
|
|
• 6 of 10 mice develop pancreatic ductal adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average survival is 24 weeks
|
|
• mutants develop lung lesions that are first detected at 12 weeks of age in alveoli and bronchioles
• mutants develop epithelial lesions termed atypical papillary bronchiolar proliferation that has papillary proliferations of the bronchiolar epithelium located at the bronchiolar terminal site
• however, no carcinomas are seen by 24 weeks of age
|
|
• mutants develop lung lesions that are first detected at 12 weeks of age in alveoli and bronchioles
• mutants develop epithelial lesions termed atypical papillary bronchiolar proliferation that has papillary proliferations of the bronchiolar epithelium located at the bronchiolar terminal site
|
|
• atypical adenomatous hyperplasia lesions and adenomas
|
|
• mutants develop lung lesions that are first detected at 12 weeks of age in alveoli and bronchioles
• mutants develop epithelial lesions termed atypical papillary bronchiolar proliferation that has papillary proliferations of the bronchiolar epithelium located at the bronchiolar terminal site
|
|
• atypical adenomatous hyperplasia lesions and adenomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival is 8 weeks
|
|
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression
|
|
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression
|
|
• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants
• mutants develop distinct bronchial and alveolar tumors
|
|
• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions
|
|
• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation
|
|
• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma
|
|
• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants
• mutants develop distinct bronchial and alveolar tumors
|
|
• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions
|
|
• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation
|
|
• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma
|
|
• by 2 months of age, mutants exhibit weight loss
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average tumor-free survival is 8.6 weeks
|
|
• 6 of 6 mice develop pancreatic ductal adenocarcinoma
|
|
• 6 of 6 mice develop pancreatic ductal adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreatic ductal adenocarcinomas
(J:87973)
• transitions of epithelium from cuboid to columnar as early as 2 weeks
(J:87973)
• extra pancreatic tumors are rare
(J:87973)
• number and extent of lesions increases with age
(J:87973)
• by 7-10 months occasional animals with invasive and metastatic adenocarcinomas
(J:87973)
• lesions eventually found in liver diaphragm and lungs
(J:87973)
• average cancer free survival is greater than 52 weeks and 2 of 9 mice develop pancreatic ductal adenocarcinoma
(J:116130)
|
|
• pancreatic intraepithelial neoplasia (PanIN)-1 lesions are distributed widely throughout the pancreas, whereas PanIN-2 or -3 lesions are rarely seen
|
|
• 6 month old mice exhibit mild acinar cell loss
|
|
• 6 month old mice exhibit mild acinar cell loss
|
|
• pancreatic ductal adenocarcinomas
(J:87973)
• transitions of epithelium from cuboid to columnar as early as 2 weeks
(J:87973)
• extra pancreatic tumors are rare
(J:87973)
• number and extent of lesions increases with age
(J:87973)
• by 7-10 months occasional animals with invasive and metastatic adenocarcinomas
(J:87973)
• lesions eventually found in liver diaphragm and lungs
(J:87973)
• average cancer free survival is greater than 52 weeks and 2 of 9 mice develop pancreatic ductal adenocarcinoma
(J:116130)
|
|
• pancreatic intraepithelial neoplasia (PanIN)-1 lesions are distributed widely throughout the pancreas, whereas PanIN-2 or -3 lesions are rarely seen
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:87973 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• shortened life span, with a median survival time of 6 months and no mice surviving past 8 months of age
|
|
• shortened life span due to lung tumors
|
|
• weekly exposure to aerosolized nontypeable Haemophilus influenzae lystate (NTHi) for 8 weeks to induce chronic obstructive pulmonary disease (COPD)-like chronic airway inflammation increases lung surface tumors 3.2-fold while no tumors are seen in NTHi treated wild-type mice
|
|
• isolated small lesions in the lungs are seen in 1- and 2-month-old mice and an increase in lesion size is seen with age
• however, no lesions are seen in other organs, including brain, liver, kidney, intestine, and muscle and no metastases are seen
• lesions are atypical papillary bronchiolar hyperplasia, solid and papillary adenomas, adenomas with atypical cytologic features, atypical papillary bronchiolar hyperplasia adjacent to adenomas, and adenoncarcinoma
• the main lesions are epithelial hyperplasia in the early stage and adenomas in the middle and late stages
• early lung lesions exhibit a Clara cell phenotype indicating that lesions come from Clara Cells of conducting airways and more advanced pathologies show an alveolar type II cell phenotype
• weekly exposure to aerosolized nontypable Haemophilus influenzae lysate results in an increase in total lung tumor burden
|
|
• lesions include solid and papillary adenomas and adenomas with atypical cytologic features
• adenomas are predominately of the papillary subtype
• number of adenomas is greater than in Krastm4Tyj Scgb1a1tm1(cre)Fjd mice but the mean size of adenomas is smaller
|
|
• mice show elevated macrophage numbers in bronchoalveolar lavage fluid (BALF)
• 14-week-old mice show focal infiltration of macrophages around hyperplastic and adenomatous lesions
• focal to extensive acidophilic pneumonia is seen surrounding adenomas and adenocarcinomas in 30% of the total lung tumors
• mice exposed to aerosolized nontypeable Haemophilus influenzae lystate (NTHi) once weekly for 8 weeks to induce chronic obstructive pulmonary disease (COPD)-like chronic airway inflammation show dense infiltration of the lung parenchyma with macrophages, neutrophils, and lymphocytes indicating neutrophil/macrophage/CD8 T cell-associated COPD-like airway inflammation; the inflammatory infiltrate is centered around airways and blood vessels, but also extends widely into alveolar spaces
|
|
• isolated small lesions in the lungs are seen in 1- and 2-month-old mice and an increase in lesion size is seen with age
• however, no lesions are seen in other organs, including brain, liver, kidney, intestine, and muscle and no metastases are seen
• lesions are atypical papillary bronchiolar hyperplasia, solid and papillary adenomas, adenomas with atypical cytologic features, atypical papillary bronchiolar hyperplasia adjacent to adenomas, and adenoncarcinoma
• the main lesions are epithelial hyperplasia in the early stage and adenomas in the middle and late stages
• early lung lesions exhibit a Clara cell phenotype indicating that lesions come from Clara Cells of conducting airways and more advanced pathologies show an alveolar type II cell phenotype
• weekly exposure to aerosolized nontypable Haemophilus influenzae lysate results in an increase in total lung tumor burden
|
|
• lesions include solid and papillary adenomas and adenomas with atypical cytologic features
• adenomas are predominately of the papillary subtype
• number of adenomas is greater than in Krastm4Tyj Scgb1a1tm1(cre)Fjd mice but the mean size of adenomas is smaller
|
|
• in early stages, epithelial hyperplasia is only seen in bronchioles, not in the alveolar sac area
• lesions include atypical papillary bronchiolar hyperplasia and atypical papillary bronchiolar hyperplasia adjacent to adenomas
|
|
• mice show elevated macrophage numbers in bronchoalveolar lavage fluid (BALF)
• 14-week-old mice show focal infiltration of macrophages around hyperplastic and adenomatous lesions
• focal to extensive acidophilic pneumonia is seen surrounding adenomas and adenocarcinomas in 30% of the total lung tumors
• mice exposed to aerosolized nontypeable Haemophilus influenzae lystate (NTHi) once weekly for 8 weeks to induce chronic obstructive pulmonary disease (COPD)-like chronic airway inflammation show dense infiltration of the lung parenchyma with macrophages, neutrophils, and lymphocytes indicating neutrophil/macrophage/CD8 T cell-associated COPD-like airway inflammation; the inflammatory infiltrate is centered around airways and blood vessels, but also extends widely into alveolar spaces
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:159271 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• shortened life span, with a median survival time of 10 months and no mice surviving past 12 months of age
|
|
• shortened life span due to lung tumors
|
|
• isolated small lesions in the lungs are seen in 4- and 6-month-old mice and an increase in lesion size is seen with age
• however, no lesions are seen in other organs, including brain, liver, kidney, intestine, and muscle and no metastases are seen
• lesions are atypical papillary bronchiolar hyperplasia, solid and papillary adenomas, adenomas with atypical cytologic features, atypical papillary bronchiolar hyperplasia adjacent to adenomas, and adenoncarcinoma
• the main lesions are epithelial hyperplasia in the early stage and adenomas in the middle and late stages
|
|
• lesions include solid and papillary adenomas and adenomas with atypical cytologic features
• adenomas are predominately of the papillary subtype
• number of adenomas is less than in Krastm4Tyj Scgb1a1tm1.1(cre)Fjd mice but the mean size of adenomas is greater
|
|
• adenocarcinomas are only seen in the very late stage
|
|
• focal to extensive acidophilic pneumonia is seen surrounding adenomas and adenocarcinomas in 30% of the total lung tumors
|
|
• isolated small lesions in the lungs are seen in 4- and 6-month-old mice and an increase in lesion size is seen with age
• however, no lesions are seen in other organs, including brain, liver, kidney, intestine, and muscle and no metastases are seen
• lesions are atypical papillary bronchiolar hyperplasia, solid and papillary adenomas, adenomas with atypical cytologic features, atypical papillary bronchiolar hyperplasia adjacent to adenomas, and adenoncarcinoma
• the main lesions are epithelial hyperplasia in the early stage and adenomas in the middle and late stages
|
|
• lesions include solid and papillary adenomas and adenomas with atypical cytologic features
• adenomas are predominately of the papillary subtype
• number of adenomas is less than in Krastm4Tyj Scgb1a1tm1.1(cre)Fjd mice but the mean size of adenomas is greater
|
|
• adenocarcinomas are only seen in the very late stage
|
|
• lesions include atypical papillary bronchiolar hyperplasia and atypical papillary bronchiolar hyperplasia adjacent to adenomas
• in early stages, epithelial hyperplasia is only seen in bronchioles, not in the alveolar sac area
|
|
• focal to extensive acidophilic pneumonia is seen surrounding adenomas and adenocarcinomas in 30% of the total lung tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:159271 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die at a median age of 26 days
|
|
• mice show progressive weight loss after 2 weeks of age
|
|
• mice show hepatosplenomegaly after 2 weeks of age
|
|
• mice exhibit an atrophied thymus
|
|
• mice exhibit an atrophied thymus
|
|
• mice show hepatosplenomegaly after 2 weeks of age
|
|
• mice show thrombocytopenia after 2 weeks of age
|
|
• mice show an increase in the frequency of CD11c+dendritic cells in the bone marrow and spleen, with expansion particularly in the atrophied thymus
• mice show histiocytic infiltrate in the spleen, liver, lung and intestines and an increase in frequency of CD11b+Gr1+ cells in the blood, bone marrow, liver, and spleen
|
|
• frequency of B220+ B lymphocytes is decreased
|
|
• frequency of CD3+ T lymphocytes is decreased
|
|
• atrophied thymus shows a deficit of CD4-CD8-CD25+ committed T cell progenitors
|
|
• atrophied thymus shows a deficit of CD4+CD8+ double-positive cells
|
|
• mice show leukocytosis after 2 weeks of age
|
|
• mice show monocytosis after 2 weeks of age
|
|
• moribund mice show a reduction hematopoietic stem cells (LSK CD150+CD48-) and multipotent progenitors (LSK CD150-CD48+) in the bone marrow and spleen
|
|
• mice exhibit an atrophied thymus
|
|
• mice show hepatosplenomegaly after 2 weeks of age
|
|
• mice show an increase in the frequency of CD11c+dendritic cells in the bone marrow and spleen, with expansion particularly in the atrophied thymus
• mice show histiocytic infiltrate in the spleen, liver, lung and intestines and an increase in frequency of CD11b+Gr1+ cells in the blood, bone marrow, liver, and spleen
|
|
• frequency of B220+ B lymphocytes is decreased
|
|
• frequency of CD3+ T lymphocytes is decreased
|
|
• atrophied thymus shows a deficit of CD4-CD8-CD25+ committed T cell progenitors
|
|
• atrophied thymus shows a deficit of CD4+CD8+ double-positive cells
|
|
• mice show leukocytosis after 2 weeks of age
|
|
• mice show monocytosis after 2 weeks of age
|
|
• mice develop a juvenile myelomonocytic leukemia-like disease
|
|
• mice show hepatosplenomegaly after 2 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| juvenile myelomonocytic leukemia | DOID:0050458 |
OMIM:607785 |
J:247853 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• intranasal instillation of an adenovirus expressing Cre recombinase (Ad-Cre) results in the development of sinonasal adenocarcinomas
• however, mice injected intramuscularly with Ad-Cre into the extremities or uterus do not develop soft tissue sarcomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• of all pIpC-treated mice faster than control mice
|
|
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster than control mice
|
|
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster than control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• of all pIpC-treated mice
|
|
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster
|
|
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• of all pIpC-treated mice faster than control mice
|
|
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster than control mice
|
|
• all pIpC-treated mice die of myeloproliferative disorder accompanied by an expansion of myeloid cells in the bone marrow, an infiltration of myeloid cells in the spleen, and the appearance of blast cells in the blood faster than control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• exhibit reduced survival than controls after 200 days of age, with a median survival of 347 days
|
|
• pancreatic tumors examined demonstrate a dominant sarcomatoid histology (50% or more) as well as the ductal adenocarcinoma
|
|
• at 200 days of age or later, show well-differentiated ductal adenocarcinoma in the pancreas head region
|
|
• develop pancreatic intraepithelial neoplasia (mPanIN) lesions predominantly in the pancreas tail region
|
|
• tumors frequently show gross metastasis to the liver and lung, direct invasion to the duodenum, and also peritoneal dissemination
• frequency of metastasis or invasion is much higher (about 50%) than in similar mutants with homozygous, instead of heterozygous, loss of Tgfbr2
|
|
• pancreatic tumors examined demonstrate a dominant sarcomatoid histology (50% or more) as well as the ductal adenocarcinoma
|
|
• at 200 days of age or later, show well-differentiated ductal adenocarcinoma in the pancreas head region
|
|
• develop pancreatic intraepithelial neoplasia (mPanIN) lesions predominantly in the pancreas tail region
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some die suddenly with a median survival of 59 days
|
|
• begin to demonstrate abdominal distension at around 6-7 weeks of age due to pancreatic tumor
|
|
• seen frequently
|
|
• 100% penetrance of pancreatic tumors
|
|
• progressive development of pancreatic ductal adenocarcinoma; tumor uniformly occupies the whole pancreas and is irregularly shaped and results in almost complete loss of normal pancreatic tissue
• carcinoma cells frequently show nuclear atypia and invasion beyond the basement membrane
• stromal expansion starts in the early tumorigenesis stages and tumors do not show sarcomatoid architecture
• 100% penetrance and tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions
|
|
• tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions
|
|
• although no distant metastasis is seen at 7-10 weeks of age, the few mutants that survive up to 24-27 weeks, show prominent desmoplasia and liver metastasis, lung metastasis, diaphragmatic and duodenal invasion and peritoneal dissemination
|
|
• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation
|
|
• at late-stage tumor burden, exhibit multiple necrotic areas in the distal liver parenchyma
|
|
• at late-stage tumor burden (7-10 weeks of age), 32% exhibit portal vein thrombosis; the main trunk of the portal vein is completely obstructed with thrombus
|
|
• frequently display bloody ascites
|
|
• seen frequently
|
|
• seen frequently
|
|
• a few mutants exhibit paraplegia, most likely because of circulation failure due to oppression of large vessels by the growing tumor
|
|
• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation
|
|
• duodenum loop is compressed by the tumor, resulting in duodenal and gallbladder dilatation
|
|
• 100% penetrance of pancreatic tumors
|
|
• progressive development of pancreatic ductal adenocarcinoma; tumor uniformly occupies the whole pancreas and is irregularly shaped and results in almost complete loss of normal pancreatic tissue
• carcinoma cells frequently show nuclear atypia and invasion beyond the basement membrane
• stromal expansion starts in the early tumorigenesis stages and tumors do not show sarcomatoid architecture
• 100% penetrance and tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions
|
|
• tumors are always accompanied by a whole panel of pancreatic intraepithelial neoplasia (mPanIN) lesions and acinar-ductal metaplasia lesions
|
|
• at late-stage tumor burden (7-10 weeks of age), 32% exhibit portal vein thrombosis; the main trunk of the portal vein is completely obstructed with thrombus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 6 month old mice exhibit severe acinar cell loss
|
|
• 6 month old mice exhibit severe acinar cell loss
|
|
• mice show accelerated pancreatic intraepithelial neoplasia (PanIN) lesions with severe acinar cell loss, with majority of lesions being PanIN-1 but having some PanIN-2 and -3 lesions
|
|
• mice show accelerated pancreatic intraepithelial neoplasia (PanIN) lesions with severe acinar cell loss, with majority of lesions being PanIN-1 but having some PanIN-2 and -3 lesions
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lung tumors from mice injected with cre- and flpo-expressing adenoviruses exhibit a doubling time of 2 weeks
|
|
• high-grade ling adenocarcinomas as early as 8 weeks after injection with cre- and flpo-expressing adenoviruses
|
|
• extremity sarcomas as early as 8 weeks after injection with cre- and flpo-expressing adenoviruses
|
|
• high-grade ling adenocarcinomas as early as 8 weeks after injection with cre- and flpo-expressing adenoviruses
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% mortality by 6 months of age
• 100% mortality by 1 year of age
|
|
• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions
|
|
• metastases develop affecting liver, diaphragm, lungs, lymph nodes, and spleen
|
|
• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:119988 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mutants show 50% survival at 44 weeks compared to 37.5 weeks in single Kras heterozygous controls, indicating a slight 22% increase in survival
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the mean lifespan of mice treated tamoxifen is 34-42 weeks
|
|
• in mice treated with tamoxifen at weaning
|
|
• in mice treated with tamoxifen at weaning
|
|
• in mice treated with tamoxifen at weaning
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:161780 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% of tamoxifen-treated mice survive at 40 weeks
|
|
• in mice treated with tamoxifen at weaning
|
|
• in mice treated with tamoxifen at weaning
|
|
• in mice treated with tamoxifen at weaning
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:161780 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated tamoxifen at weaning exhibit an increase in lifespan of 8 weeks (42 weeks) compared with similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd littermates (34 weeks)
|
|
• tamoxifen-treated mice exhibit reduced tumor burden compared with similarly treated Krastm1Bbd/Kras+ Polr2atm1(cre/ERT2)Bbd/Polr2atm1(cre/ERT2)Bbd mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation compared to single Kras heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mice show 50% survival at 41.5 weeks compared to 40 weeks in single Kras heterozygous controls, indicating similar survival
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% survival at 34.9 weeks versus 31.2 weeks in single Kras mutants following intratracheal instillation of Ad-Cre, indicating a 16% increase in survival
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• latency to develop lung adenomas is significantly shorter compared to double mutants wild-type for Cdk4; however development of tumors characteristic of Cdk4tm1.1Bbd mutant mice is not accelerated
|
|
• histiocytic sarcoma and other sarcomas are seen
|
|
• anal papillomas are seen
|
|
• focal metaplasia in the pancreatic ducts consisting of tall columnar cells with abundant apical mucin resembling gastric surface epithelial cells
|
|
• focal metaplasia in the pancreatic ducts consisting of tall columnar cells with abundant apical mucin resembling gastric surface epithelial cells
|
|
• latency to develop lung adenomas is significantly shorter compared to double mutants wild-type for Cdk4; however development of tumors characteristic of Cdk4tm1.1Bbd mutant mice is not accelerated
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants develop breathing difficulties after 7 - 8 months of age
|
|
• frequent embryonic lethality; however, a significant number of double mutants survive
|
|
• a large spectrum of multifocal lesions are seen in the lung including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes
|
|
• large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes
|
|
• histiocytic sarcoma and other sarcomas seen in 2 out of 20 and 3 out of 20 double mutants, respectively
|
|
• anal papillomas seen in 3 out of 20 double mutants
|
|
• MEFs expressing the oncogenic protein do not undergo proliferative senescence and proliferate continuously as immortal cells
|
|
• a large spectrum of multifocal lesions are seen in the lung including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes
|
|
• large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes
|
|
• double mutants develop breathing difficulties after 7 - 8 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice live up to 40 weeks
|
|
• by 24 weeks, mice develop tumors in the thymus
|
|
• by 24 weeks, mice develop tumors in lungs
|
|
• at 4 weeks after 5-hydroxytamoxifen treatment, a few small adenomas are observed in some animals
|
|
• by 24 weeks, mice develop tumors in lungs
|
|
• at 4 weeks after 5-hydroxytamoxifen treatment, a few small adenomas are observed in some animals
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb
|
|
• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenocarcinomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb
|
|
• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb
|
|
• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenocarcinomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die before week 32 due to increased lung cancer progression
|
|
• 20 weeks after treatment, lungs are increased in size
|
|
• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs
• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices
• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass
|
|
• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14tm2Nbr/+ control mice
|
|
• adenocarcinomas are detected at 15 weeks but not in controls
|
|
• lung differentiation is abnormal with increased SP-C-positive cells
|
|
• mice also have tumors in the thymus and organs such as kidney and liver by 24 weeks after treatment whereas controls only have tumors in lungs and thymus
|
|
• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs
• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices
• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass
|
|
• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14tm2Nbr/+ control mice
|
|
• adenocarcinomas are detected at 15 weeks but not in controls
|
|
• 20 weeks after treatment, lungs are increased in size
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• at 200 days, 100% of mice exhibit atypical hyperplasia unlike wild-type mice
• at 500 days, 93% of mice exhibit atypical hyperplasia unlike wild-type mice
|
|
|
• in 7% of mice at 500 days
|
|
|
• at 200 days, 67% of mice develop prostate intraepithelial neoplasia that display foci of small solid and cribiform intraluminal proliferation of atypical cells and nuclear atypia unlike wild-type mice
• at 500 days, 60% of mice exhibit prostate intraepithelial neoplasia unlike in wild-type mice
|
|
|
• in 7% of mice at 500 days
|
|
|
• at 200 days, 67% of mice develop prostate intraepithelial neoplasia that display foci of small solid and cribiform intraluminal proliferation of atypical cells and nuclear atypia unlike wild-type mice
• at 500 days, 60% of mice exhibit prostate intraepithelial neoplasia unlike in wild-type mice
|
|
|
• at 200 days, 100% of mice exhibit atypical hyperplasia unlike wild-type mice
• at 500 days, 93% of mice exhibit atypical hyperplasia unlike wild-type mice
|
|
|
• in 7% of mice at 500 days
|
|
|
• at 200 days, 67% of mice develop prostate intraepithelial neoplasia that display foci of small solid and cribiform intraluminal proliferation of atypical cells and nuclear atypia unlike wild-type mice
• at 500 days, 60% of mice exhibit prostate intraepithelial neoplasia unlike in wild-type mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:143034 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die prior to day 300
|
|
|
• mice exhibit keratinized squamous metaplasia in the bulbourethral gland unlike wild-type mice
|
|
|
• all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice
|
|
|
• all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice
|
|
• mice exhibit keratinized squamous metaplasia in the urethral gland unlike wild-type mice
|
|
|
• mice exhibit keratinized squamous metaplasia in the bulbourethral gland unlike wild-type mice
|
|
|
• all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice
|
|
• mice exhibit keratinized squamous metaplasia in the urethral gland unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop pancreatic intraepithelial neoplasia (mPanIN) lesions within a large amount of normal pancreas
|
|
• develop pancreatic intraepithelial neoplasia (mPanIN) lesions within a large amount of normal pancreas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants treated with 4-hydroxy-tamoxifen at 10 days of age develop breathing difficulties after 7 - 8 months of age
|
|
• after treatment with 4-hydroxy-tamoxifen at 10 days of age, a large spectrum of multifocal lesions are seen in the lung at 7-8 months of age including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes
|
|
• after treatment with 4-hydroxy-tamoxifen at 10 days of age, at 7-8 months of age large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes are seen
|
|
• MEFs expressing the oncogenic protein do not undergo proliferative senescence and proliferate continuously as immortal cells
|
|
• after treatment with 4-hydroxy-tamoxifen at 10 days of age, a large spectrum of multifocal lesions are seen in the lung at 7-8 months of age including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes
|
|
• after treatment with 4-hydroxy-tamoxifen at 10 days of age, at 7-8 months of age large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes are seen
|
|
• double mutants treated with 4-hydroxy-tamoxifen at 10 days of age develop breathing difficulties after 7 - 8 months of age
|
|
• hyperplastic Harderian gland seen in double mutants treated with 4-hydroxy-tamoxifen at 10 days of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreas of older mice exhibit some areas of fatty degeneration
• however, acinar to ductal metaplasia observed in acini from Krastm4Tyj Ptf1atm1(cre)Hnak double heterozygotes is rescued in an in vitro assay
|
| N |
• pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma observed in Krastm4Tyj Ptf1atm1(cre)Hnak double heterozygotes is rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following induction of expression using an adenoviral cre, mice develop lung tumors as in Krastm4Tyj
|
|
• following induction of expression using an adenoviral cre, mice develop lung tumors as in Krastm4Tyj
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die between E9.5 and 11.5
|
|
• at E9.5 vasculature is poorly developed; vasculature has a primitive honeycomb-like network lacking branching vitelline vessels, while large vitelline vessels are absent
|
|
• at death, embryos exhibit widespread apoptosis
|
|
• embryos show developmental arrest
|
|
• marked defect in inner labyrinth layer is observed at E9.5
|
|
• fetal blood vessels underlying inner labyrinth layer are absent
|
|
• at E9.5, yolk sacs are pale and roughened
|
|
• at death, embryos exhibit widespread apoptosis
|
|
• fetal blood vessels underlying inner labyrinth layer are absent
|
|
• at E9.5 vasculature is poorly developed; vasculature has a primitive honeycomb-like network lacking branching vitelline vessels, while large vitelline vessels are absent
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• adult mice develop widespread hyperplasia throughout the colonic epithelium
|
|
• hyperplasia is typified by lengthening of the crypts in adult mice
|
|
• large, prominent goblet cells develop in the colon in adult mice
|
|
• hyperplasia is typified by lengthening of the crypts in adult mice
|
|
• large, prominent goblet cells develop in the colon in adult mice
|
|
• large, prominent goblet cells develop in the colon in adult mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 83% of mice develop tumors ranging from grades 1 to 3 at 6 weeks post intranasal adenoviral cre (AdCre) administration
|
|
• 83% of mice develop tumors ranging from grades 1 to 3 at 6 weeks post intranasal adenoviral cre (AdCre) administration
|
|
• 100% of mice show epithelial hyperplasia at 6 weeks post intranasal AdCre administration
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:216266 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a 2.9-fold increase in tumor burden compared to single Kras heterozygotes at 12 weeks post intranasal AdCre administration
• lung tumors from intranasally AdCre treated mice show enhanced stromal reactivity and inflammation
• 100% of mice develop lung lesions at 6 weeks post intranasal adenoviral cre (AdCre) administration, ranging from grades 1 to 3
• mice show accelerated lung tumorigenesis, with more advanced and higher-grade tumors post intranasal AdCre administration compared to single Kras heterozygotes
|
|
• 100% of mice develop lung lesions at 6 weeks post intranasal adenoviral cre (AdCre) administration, ranging from grades 1 to 3
• mice show accelerated lung tumorigenesis, with more advanced and higher-grade tumors post intranasal AdCre administration compared to single Kras heterozygotes
• a 2.9-fold increase in tumor burden compared to single Kras heterozygotes at 12 weeks post intranasal AdCre administration
• lung tumors from intranasally AdCre treated mice show enhanced stromal reactivity and inflammation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:216266 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice delivered with an adenovirus expressing cre recombinase through nasal inhalation at 8 weeks of age show normal lungs and do not develop lung tumors, and show only small neoplastic regions, indicating inhibition of tumor development that is seen in single Krastm4Tyj mice
|
|
• most mice delivered with an adenovirus expressing cre recombinase through nasal inhalation at 8 weeks of age show normal lungs and do not develop lung tumors, and show only small neoplastic regions, indicating inhibition of tumor development that is seen in single Krastm4Tyj mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 5 of 14 mice delivered with an adenovirus expressing cre recombinase through nasal inhalation at 8 weeks of age develop lung tumors compared to single Krastm4Tyj mice in which all mice develop tumors, indicating reduced tumor development
|
|
• 5 of 14 mice delivered with an adenovirus expressing cre recombinase through nasal inhalation at 8 weeks of age develop lung tumors compared to single Krastm4Tyj mice in which all mice develop tumors, indicating reduced tumor development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with a cre-expressing adenovirus exhibit increased tumor burden due to increased lung cancer cell proliferation compared with Krastm4Tyj heterozygotes treated with a cre-expressing adenovirus
|
|
• in mice treated with a cre-expressing adenovirus
|
|
• in mice treated with a cre-expressing adenovirus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice intratracheally administered an adenovirus expressing cre recombinase (Ad-cre) develop lung tumors with a survival rate similar to single mutant Kras homozygous mice
|
|
• mice intratracheally administered an adenovirus expressing cre recombinase (Ad-cre) develop lung tumors with a survival rate similar to single mutant Kras homozygous mice
|
|
• mice intratracheally administered Ad-cre have a median survival time as single mutant Kras homozygous mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following infection with adenovirus-FLPe/IRES/Cre (Ad-FIC)
|
|
• following infection with Ad-FIC
|
|
• following infection with adenovirus-FLPe/IRES/Cre (Ad-FIC)
|
|
• following infection with Ad-FIC
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:187012 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median life span of cre adenovirus-treated mice is 20 weeks
|
|
• tumors from cre adenovirus-treated mice exhibit lower cell proliferation rates compared to in tumors from Krastm4Tyj heterozygotes
|
|
• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas, and bronchiolar hyperplasia and dysplasia
• at end stage, 25% of cre adenovirus-treated mice develop grade 5 tumors, defined by stromal desmoplasia
• cre adenovirus-treated mice develop more numerous tumors than in cre adenovirus-treated Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
|
|
• in cre adenovirus-treated mice
|
|
• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas, and bronchiolar hyperplasia and dysplasia
• at end stage, 25% of cre adenovirus-treated mice develop grade 5 tumors, defined by stromal desmoplasia
• cre adenovirus-treated mice develop more numerous tumors than in cre adenovirus-treated Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
|
|
• in cre adenovirus-treated mice
|
|
• cre adenovirus-treated mice develop bronchiolar hyperplasia and dysplasia unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median life span of cre adenovirus-treated mice is 25 weeks
|
|
• tumors from cre adenovirus-treated mice exhibit lower cell proliferation rates compared to in tumors from Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rb1tm3Tyj/Rb1tm3Tyj mice
|
|
• cre adenovirus-treated mice develop larger tumors than in cre adenovirus-treated Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rb1tm3Tyj/Rb1tm3Tyj mice
|
|
• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas and bronchiolar hyperplasia and dysplasia
|
|
• in cre adenovirus-treated mice
|
|
• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas and bronchiolar hyperplasia and dysplasia
|
|
• in cre adenovirus-treated mice
|
|
• in cre-adenovirus-treated mice
|
|
• cre adenovirus-treated mice develop bronchiolar hyperplasia and dysplasia unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop multiple, aggressive adenocarcinomas in the lungs bilaterally following intranasal delivery of an adenovirus expressing Cre recombinase
• tumor growth is reduced more following two 7.3 Gy fractions of radiation therapy than a single 11.6 Gy fraction
• tumors have decreased BrdU uptake 4 hours after radiation treatment compared to unirradiated tumors, indicating the presence of an intact G1 cell-cycle checkpoint
|
|
• mice develop multiple, aggressive adenocarcinomas in the lungs bilaterally following intranasal delivery of an adenovirus expressing Cre recombinase
• tumor growth is reduced more following two 7.3 Gy fractions of radiation therapy than a single 11.6 Gy fraction
• tumors have decreased BrdU uptake 4 hours after radiation treatment compared to unirradiated tumors, indicating the presence of an intact G1 cell-cycle checkpoint
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:195492 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop pancreatic tumors unlike Krastm4Tyj/Kras+ Tg(Ela1-cre/ERT)1Dam mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
(J:103407)
• following cre-adenovirus treatment, tumors occupy 27% of lung space
(J:103407)
• mice treated with intratracheal delivery of cre-expressing adenovirus develop lung cancer
(J:191425)
• mice infected with higher doses of cre expressing adenovirus present with clinical signs of lung cancer by 15 weeks of treatment while lower dosed animals show signs of disease around 37 weeks
(J:191425)
• a subset of tumors from mice treated with intratracheal delivery of cre-expressing adenovirus show loss of heterozygosity of Trp53
(J:191425)
• treatment of mice treated with intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus almost completely abrogates tumor formation
(J:191425)
• treatment of mice that have already formed lung tumors following intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus prevents further progression of tumors
(J:191425)
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus show evidence that high-grade adenocarcinomas acquire metastatic characteristics of non-small cell lung cancer
|
|
• tumors of mice treated with intratracheal delivery of cre-expressing adenovirus are adenocarcinomas and some evidence that high-grade adenocarcinomas acquire metastatic characteristics
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit large lungs filled with tumors and inflammation
• the inflammation that develops in the lungs of mice treated with intratracheal delivery of cre-expressing adenovirus occurs after initial nodules develop
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus develop a hunched posture in the most severe cases
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit a decline in weight
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit large lungs filled with tumors and inflammation
• the inflammation that develops in the lungs of mice treated with intratracheal delivery of cre-expressing adenovirus occurs after initial nodules develop
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
(J:103407)
• following cre-adenovirus treatment, tumors occupy 27% of lung space
(J:103407)
• mice treated with intratracheal delivery of cre-expressing adenovirus develop lung cancer
(J:191425)
• mice infected with higher doses of cre expressing adenovirus present with clinical signs of lung cancer by 15 weeks of treatment while lower dosed animals show signs of disease around 37 weeks
(J:191425)
• a subset of tumors from mice treated with intratracheal delivery of cre-expressing adenovirus show loss of heterozygosity of Trp53
(J:191425)
• treatment of mice treated with intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus almost completely abrogates tumor formation
(J:191425)
• treatment of mice that have already formed lung tumors following intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus prevents further progression of tumors
(J:191425)
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus show evidence that high-grade adenocarcinomas acquire metastatic characteristics of non-small cell lung cancer
|
|
• tumors of mice treated with intratracheal delivery of cre-expressing adenovirus are adenocarcinomas and some evidence that high-grade adenocarcinomas acquire metastatic characteristics
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit labored breathing
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:191425 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are shifted towards more lower grade tumor types
• following cre-adenovirus treatment, tumors occupy 36% of lung space
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are shifted towards more lower grade tumor types
• following cre-adenovirus treatment, tumors occupy 36% of lung space
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• infiltrating inflammatory cells recruited to tumors in which NF-kB has been inhibited
• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses
|
|
• doxycycline (Dox)-mediated induction of Nfkbia expression specifically in the tumor cells starting at 16 weeks after tumor initiation results in a significantly diminished tumour growth rate
• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses
|
|
• doxycycline (Dox)-mediated induction of Nfkbia expression specifically in the tumor cells leads to a significant impairment of tumour development
• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection
|
|
|
• mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection
|
|
|
• mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:161953 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after treatment with adenoviral cre, mice develop a significantly increased lung tumor burden unlike mice having mutations in only one of the two transactivation domains with normal tumor levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants
|
|
• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants
|
|
• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• numbers of stained spots in intestines is not increased compared to mice without the Kras allele, but size of stained patches increases suggesting sporadic cre activation of Kras which might have a selective advantage for mutant stem cells resulting in clonal expansion and crypt fission
|
|
• animals become moribund at 5 weeks of age due to high lung tumor burden
|
|
• numbers of stained spots in intestines is not increased compared to mice without the Kras allele, but size of stained patches increases suggesting sporadic cre activation of Kras which might have a selective advantage for mutant stem cells resulting in clonal expansion and crypt fission
|
|
• animals become moribund at 5 weeks of age due to high lung tumor burden
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• homozygous embryos die by E14.5
|
|
• embryos are recovered at a lower frequency (15% vs expected 25%) at E13.5
|
| N |
• mutants show normal vascularization of the yolk sac and placental labyrinth
|
|
• fetal-derived hematopoietic progenitors form larger CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) colonies compared with controls
|
|
• excess cushion tissue often leads to obstructed outflow tract
|
|
• at E13.5, embryos frequently show double outlet right ventricle
|
|
• atrioventricular valve malformations
|
|
• all embryonic hearts have prominent septal defects
|
|
• heart defects lead to heart failure and death in embryos by ~E14.5
|
|
• embryos appear normal at E12.5, but rapidly develop peripheral hemorrhages by E13.5, consistent with heart failure
|
|
• red blood cells appear immature compared to wild-type and occasionally highly atypical, consisten with a block in erythroid differentiation
|
|
• fetal-derived hematopoietic progenitors form larger CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) colonies compared with controls
|
|
• defects in lung branching are apparent by E11.5 compared to controls in vivo and in cultured lungs
• decrease in branching is associated with formation of large, fluid-filled sacs rather than normal terminal branches
|
|
• at E12.5, mutant lungs exhibit large dilated bronchi whereas wild-type lungs show secondary and tertiary bronchi
• at E14.5, mutants lungs display dilated bronchi and only a few terminal bronchi
|
|
• at E14.5, mutants lungs display only a few terminal bronchioles
|
|
• at E12.5, lungs exhibit large dilated bronchi; defect is more pronounced at E14.5
|
|
• at E12.5, lungs exhibit large dilated bronchi; defect is more pronounced at E14.5
|
|
• at E12.5 fetal livers show large areas of apoptosis
|
|
• at E12.5, fetal livers appear hypocellular
|
|
• embryos appear normal at E12.5, but rapidly develop edema by E13.5, consistent with heart failure
|
|
• embryos appear normal at E12.5, but rapidly develop pallor by E13.5, consistent with heart failure
|
|
• at E12.5 fetal livers show large areas of apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival 25.5 weeks
|
|
• starting between 6 and 24 weeks with metastasis
|
|
• adenocarcinomas in 9 of 9 invasive carcinomas in the pancreas
|
|
• adenocarcinomas in 9 of 9 invasive carcinomas in the pancreas
|
|
• starting between 6 and 24 weeks
|
|
• increased girth starting between 6 and 24 weeks
|
|
• starting between 6 and 24 weeks with metastasis
|
|
• adenocarcinomas in 9 of 9 invasive carcinomas in the pancreas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop acinar to ductal metaplasia
|
| N |
• mice do not develop pancreatic intraepithelial neoplasia or pancreatic ductal adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following administration of inhaled adenovirus cre
|
|
• following administration of inhaled adenovirus cre
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2-4 months after tamoxifen treatment, lip tumors develop in 78% of treated mice
|
|
• 2-4 months after tamoxifen treatment, tumors develop in the back skin in 33% of treated mice
|
|
• skin tumors are benign papillomas with no sign of malignant transformation seen up to 4 months after treatment with tamoxifen
|
|
• 2-4 months after tamoxifen treatment, lip tumors develop in 78% of treated mice
|
|
• 2-4 months after tamoxifen treatment, lip tumors develop in 78% of treated mice
|
|
• sebaceous cyst formation is observed as result of bulge stem cell proliferation and abnormal hair follicle (HF) differentiation
|
|
• 1 month after tamoxifen treatment, Kras activation results in the enlargement of the majority of sebaceous glands
|
|
• 1 month after tamoxifen treatment, Kras activation results in transient increase in hair follicle bulge stem cell (SC) proliferation
• hyperproliferative bulge SCs can still undergo terminal differentiation
|
|
• 2-4 months after tamoxifen treatment, tumors develop in the back skin in 33% of treated mice
|
|
• skin tumors are benign papillomas with no sign of malignant transformation seen up to 4 months after treatment with tamoxifen
|
|
• sebaceous cyst formation is observed as result of bulge stem cell proliferation and abnormal hair follicle (HF) differentiation
|
|
• 1 month after tamoxifen treatment, Kras activation results in the enlargement of the majority of sebaceous glands
|
|
• 1 month after tamoxifen treatment, Kras activation results in transient increase in hair follicle bulge stem cell (SC) proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following administration of inhaled adenovirus cre
|
|
• following administration of inhaled adenovirus cre
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following administration of inhaled adenovirus cre, mice develop fewer lung tumors than in Krastm4Tyj/Kras+ Pik3r2tm1Lca/Pik3r2tm1Lca or Krastm4Tyj/Kras+ Pik3r2tm1Lca/Pik3r2tm1Lca Pik3r1tm1Lca/Pik3r1+ mice
|
|
• following administration of inhaled adenovirus cre, mice develop fewer lung tumors than in Krastm4Tyj/Kras+ Pik3r2tm1Lca/Pik3r2tm1Lca or Krastm4Tyj/Kras+ Pik3r2tm1Lca/Pik3r2tm1Lca Pik3r1tm1Lca/Pik3r1+ mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no epidermal defects or tumor formation are observed with tamoxifen treatment at day 28 (during period of up to 4 months after cre induction) when hair follicles are in full anlagen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the lungs of mice treated with cre-expressing adenovirus
|
|
• in the lungs of mice treated with cre-expressing adenovirus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit reduced survival compared with control mice
|
|
• mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit increased tumor incidence (size and number) in the lungs with rare noninvasive lung adenomas compared with control mice
• however, mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit tumor regression after doxycycline removal
|
|
• in mice treated with a cre-expressing adenovirus and treated with doxycycline
|
|
• in mice treated with a cre-expressing adenovirus and treated with doxycycline
|
|
• rapid shallow breathing in mice treated with a cre-expressing adenovirus and treated with doxycycline
|
|
• in mice treated with a cre-expressing adenovirus and treated with doxycycline
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pIpC-induced mice die prematurely but at an older age than induced conditional Krastm4Tyj mice
|
|
• mice induced with polyinosinic:polycytidylic acid (pIpC) develop a myelodysplastic syndrome/myeloproliferative neoplasm that is qualitatively similar to that seen in conditional Krastm4Tyj mice, but with a delayed onset
|
|
• dying pIpC-induced mice show splenomegaly
|
|
• hemoglobin levels decline over time in pIpC-induced mice
|
|
• white blood cell counts slowly rise over time in pIpC-induced mice
|
|
• expansion of immature myeloid cells in the bone marrow and spleen in pIpC-induced mice
|
|
• expansion of immature myeloid cells in the bone marrow of pIpC-induced mice
|
|
• dying pIpC-induced mice show splenomegaly
|
|
• white blood cell counts slowly rise over time in pIpC-induced mice
|
|
• dying pIpC-induced mice show splenomegaly
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance
|
|
• tumors that develop after RU486 induction are well-to-moderately differentiated squamous cell carcinomas with an epidermal lineage or basaloid squamous cell carcinomas of unknown stem cell origin
|
|
• a subset of benign or locally invasive tumors form adjacent to the squamous cell carcinoma precursor lesions, which are of hair follicle (trichoepitheliomas, basaloid squamous cell carcinoma) or sebaceous gland origin (sebaceous adenomas) after induction with topical application of RU486
|
|
• metastases develop between 8 and 18 weeks after induction with RU486, with 28% of tumor-bearing mice developing lung metastasis and 1 of 18 mice showing lymph node metastasis
|
|
• a subset of benign or locally invasive tumors form adjacent to the squamous cell carcinoma precursor lesions, which are of hair follicle (trichoepitheliomas, basaloid squamous cell carcinoma) or sebaceous gland origin (sebaceous adenomas) after induction with topical application of RU486
|
|
• a few benign papillomas are seen after induction with topical application of RU486
|
|
• mice rapidly develop skin tumors beginning 1 month after induction with topical application of RU486 to the back of the skin with 100% penetrance
|
|
• tumors that develop after RU486 induction are well-to-moderately differentiated squamous cell carcinomas with an epidermal lineage or basaloid squamous cell carcinomas of unknown stem cell origin
|
|
• a subset of benign or locally invasive tumors form adjacent to the squamous cell carcinoma precursor lesions, which are of hair follicle (trichoepitheliomas, basaloid squamous cell carcinoma) or sebaceous gland origin (sebaceous adenomas) after induction with topical application of RU486
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| squamous cell carcinoma | DOID:1749 | J:203922 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop pancreatic ductal adenocarcinoma (PDAC)
|
|
• mice develop pancreatic ductal adenocarcinoma (PDAC)
|
|
• GFP+ PDAC cells form tumors form more metastases than GFP- PDAC cells when transplanted into recipient mice
• the highly metastatic PDAC subpopulation is enriched for hypoxia-induced genes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:245611 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit increased cell proliferation in the colonic crypt compared with wild-type mice
|
|
• mice exhibit increased cell proliferation in the colonic crypt compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a median survival of 24 weeks after ad-cre inoculation
|
|
• 3 of 15 (20%) ad-cre inoculated mice exhibit metastasis
|
|
• mice inoculated with ad-cre by inhalation develop infrequent highly lethal tumors; all tumors are adenocarcinomas
|
|
• mice inoculated with ad-cre by inhalation develop infrequent highly lethal tumors; all tumors are adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 9 of 12 mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
|
• median lifespan is approximately 120 days with all mice dying around 260 days, which is extended survival compared to conditional mice expressing the Krastm4Tyj allele
|
|
• 9 of 12 mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:276349 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a median survival of 9 weeks after ad-cre inoculation
|
|
• regional lymph-node metastases and axial skeleton metastases are seen in 61% of ad-cre inoculated mice
|
|
• mice inoculated with ad-cre develop lung tumors; tumor burden is increased at early time points and larger lesions at later time points are seen than in single Kras mutants
|
|
• adenocarcinoma is seen in all metastatic lesions
|
|
• 2 of 27 ad-cre treated mice show large cell carcinoma
|
|
• 56% of ad-cre treated mice develop squamous cell carcinomas (SCCs) or adenosquamous carcinomas
• squamous tumors do not express pro-surfactant protein, but express pan-keratin and p63, markers of SCC
|
|
• mice inoculated with ad-cre develop lung tumors; tumor burden is increased at early time points and larger lesions at later time points are seen than in single Kras mutants
|
|
• adenocarcinoma is seen in all metastatic lesions
|
|
• 2 of 27 ad-cre treated mice show large cell carcinoma
|
|
• 56% of ad-cre treated mice develop squamous cell carcinomas (SCCs) or adenosquamous carcinomas
• squamous tumors do not express pro-surfactant protein, but express pan-keratin and p63, markers of SCC
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung non-small cell carcinoma | DOID:3908 | J:124682 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a mean survival of 9 weeks after ad-cre inoculation
|
|
• regional lymph-node metastases and axial skeleton metastases are seen in 61% of ad-cre inoculated mice
|
|
• mice inoculated with ad-cre develop lung tumors; tumor burden is increased at early time points and larger lesions at later time points are seen than in single Kras mutants
|
|
• adenocarcinoma is seen in all metastatic lesions
|
|
• 2 of 27 ad-cre treated mice show large cell carcinoma
|
|
• 56% of ad-cre treated mice develop squamous cell carcinomas (SCCs) or adenosquamous carcinomas
• squamous tumors do not express pro-surfactant protein, but express pan-keratin and p63, markers of SCC
|
|
• mice inoculated with ad-cre develop lung tumors; tumor burden is increased at early time points and larger lesions at later time points are seen than in single Kras mutants
|
|
• adenocarcinoma is seen in all metastatic lesions
|
|
• 2 of 27 ad-cre treated mice show large cell carcinoma
|
|
• 56% of ad-cre treated mice develop squamous cell carcinomas (SCCs) or adenosquamous carcinomas
• squamous tumors do not express pro-surfactant protein, but express pan-keratin and p63, markers of SCC
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung non-small cell carcinoma | DOID:3908 | J:124682 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show moderate colon epithelium crypt hyperplasia that is intermediate between wild-type mice and conditional Krastm4Tyj mice
|
|
• colons show an intermediate hyperproliferative phenotype compared to wild-type mice or conditional Krastm4Tyj mice
• Paneth cells are intact in colons
|
|
• mice show moderate colon epithelium crypt hyperplasia that is intermediate between wild-type mice and conditional Krastm4Tyj mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop colonic tumors, characterized as adenomas with low-grade dysplasia
|
|
• mice show slightly longer survival than conditional mice carrying the Krastm4Tyj allele
|
|
• mice develop colonic tumors, characterized as adenomas with low-grade dysplasia
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:276349 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival of mice infected with RCASBP(A)-shTP53, which knocks down Trp53 expression, is only 151 days compared to 485 days for controls
|
|
• mice infected with RCASBP(A)-shTP53, which knocks down Trp53 expression, display a significantly shorter latency of pancreatic ductal adenocarcinoma development
• all infected mice develop invasive pancreatic ductal adenocarcinoma within 10 months
|
|
• mice infected with RCASBP(A)-shTP53, which knocks down Trp53 expression, display a significantly shorter latency of pancreatic ductal adenocarcinoma development
• all infected mice develop invasive pancreatic ductal adenocarcinoma within 10 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice administered tamoxifen at P1 show early lethality beginning at P12
|
| N |
• mice administered tamoxifen at P1fail to show frequent cranial hemorrhage or cortical brain arteriovenous malformations (bAVMs) at P14 or P21
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival 15.5 weeks
|
|
• starting between 6 and 24 weeks with metastasis
|
|
• adenocarcinomas in 21 of 22 invasive carcinomas in the pancreas
|
|
• adenocarcinomas in 21 of 22 invasive carcinomas in the pancreas
|
|
• starting between 6 and 24 weeks
|
|
• increased girth starting between 6 and 24 weeks
|
|
• starting between 6 and 24 weeks with metastasis
|
|
• adenocarcinomas in 21 of 22 invasive carcinomas in the pancreas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 1 year of age, 44% of mutants develop skin papilloma, with tumors reaching 1 cm in diameter by a median of 220 days
|
|
• shorter survival due to skin papillomas, with a survival time between 100-400 days
|
| N |
• mice aged to 12 month do not develop urothelial hyperplasia or urothelial carcinoma or lung tumors
|
|
• by 1 year of age, 44% of mutants develop skin papilloma, with tumors reaching 1 cm in diameter by a median of 220 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice succumb to invasive pancreatic neoplasms
|
|
• rapid progression, multi-focal and invasive
• pancreatic ductal adenocarcinoma or invasive cystic neoplasms with metastasis to the liver and lungs
|
|
• rapid progression, multi-focal and invasive
• pancreatic ductal adenocarcinoma or invasive cystic neoplasms with metastasis to the liver and lungs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• female mutants develop granulosa cell tumors by 12-14 weeks of age
|
|
|
• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
|
|
|
• female mutants develop granulosa cell tumors by 12-14 weeks of age
|
|
|
• seminiferous tubule degeneration is seen by 4 weeks of age
|
|
|
• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
|
|
|
• female mutants develop granulosa cell tumors by 12-14 weeks of age
|
|
|
• seminiferous tubule degeneration is seen by 4 weeks of age
|
|
|
• male mutants develop granulosa cell tumors of the testis by 4-5 months of age; tumors do not spread or metastasize
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| granulosa cell tumor | DOID:2999 | J:186144 | ||
| juvenile type testicular granulosa cell tumor | DOID:6032 | J:186144 | ||
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• extended survival compared to control mice with normal Brf1
|
|
• at a reduced rate and with extended survival compared to control mice with normal Brf1
• however, tumors that do form lack recombined Brf1
|
|
• at a reduced rate and with extended survival compared to control mice with normal Brf1
• however, tumors that do form lack recombined Brf1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die within 3.5-5.5 months of age
|
|
|
• female mutants exhibit precancerous lesions in the ovaries at between 4 and 5 weeks of age
|
|
|
• female mutants develop bilateral granulosa cell tumors by 3 months of age
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
|
|
• female mutants exhibit precancerous lesions in the ovaries at between 4 and 5 weeks of age
|
|
|
• female mutants develop bilateral granulosa cell tumors by 3 months of age
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
|
|
• female mutants exhibit precancerous lesions in the ovaries at between 4 and 5 weeks of age
|
|
|
• female mutants develop bilateral granulosa cell tumors by 3 months of age
|
|
|
• at 6 weeks of age in females
|
|
|
• at 6 weeks of age in females
|
|
|
• at 6 weeks of age in females
|
|
|
• at 6 weeks of age in females
|
|
|
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| granulosa cell tumor | DOID:2999 | J:186144 | ||
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:186144 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival of 185 days and median survival of 200 days
|
|
• mice rapidly develop bladder tumors resembling urothelial cell carcinoma
|
|
• mice rapidly develop bladder tumors resembling urothelial cell carcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:234236 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age
• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers
• rare metastasis to lungs is seen
|
|
• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age
• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions
|
|
• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age
|
|
• median survival time is about 3.5 months
|
|
• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age
• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers
• rare metastasis to lungs is seen
|
|
• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age
• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions
|
|
• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age
|
|
• acinar-to-ductal metaplasia is seen at 1-3 months of age, concentrated in the transition zone between morphologically normal pancreatic structures and mPanIN and PDAC lesions
• acinar-to-ductal metaplasia development precedes mPanIN formation
• metaplastic lesions show an increase in CD44+ cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:164210 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival for around 35 days after pI-pC treatment
• survival of around 58 days even without pI-pC treatment
|
|
• 7 of 25 mice injected with pIpC develop thymic T cell lymphoblastic lymphomas
• 2 of 6 non pIpC treated mice show thymic lymphomas
|
|
• 10 of 17 mice injected with pIpC exhibit multiple nodules in the lungs consisting of proliferating type II penumocytes
• 5 of 6 non pIpC treated mice show pulmonary adenomas
|
|
• squamous papillomas
|
|
• 8 of 25 mice injected with pIpC develop squamous papillomas involving the oral mucosa
• 2 of 6 non-pIpC treated mice show oral squamous papillomas
|
|
• 8 of 22 mice injected with pIpC develop squamous papillomas involving the esophageal mucosa
|
|
• 12 of 19 mice injected with pIpC develop squamous papillomas involving the anal and vulvo-vaginal skin and 8 of 22 mice develop squamous papillomas involving the ear
• 2 of 6 non-pIpC treated mice show ear squamous papillomas
|
|
• 8 of 25 mice injected with pIpC develop squamous papillomas involving the oral mucosa
• 2 of 6 non-pIpC treated mice show oral squamous papillomas
|
|
• mice injected with pIpC develop moderate to severe splenomegaly
|
|
• 7 of 25 mice injected with pIpC develop thymic T cell lymphoblastic lymphomas
• 2 of 6 non pIpC treated mice show thymic lymphomas
|
|
• mice injected with pIpC develop moderate to severe splenomegaly
|
|
• develop lethal hematopoietic disease
|
|
• 4-7 week old mice injected with pIpC develop a myeloproliferative disorder
• bone marrow of mice injected with pIpC shows myelomonocytic expansion
• all mice that are not treated with pIpC also develop a hematopoietic disease, however these mice exhibit expression of the mutant Kras, indicating that most likely endogenous IFN expression is sufficient to induce the cre transgene
• bone marrow cells from pIpC injected mice readily form colonies, predominately monocyte colony-forming units (M-CFUs) in a growth factor-independent manner unlike controls
|
|
• myeloproliferative phenotype
• myeloid hyperplasia of bone marrow
|
|
• expansion of red pulp in spleen by granulocyte/monocyte lineages in 11 out of 16 cases
• erythroid expansion was seen in red pulp of spleen in 5 of 16 cases
• the liver shows perivascular and periportal infiltration by myeloid and erythroid cell populations
|
|
• mice injected with pIpC have a mean hematocrit of 27% compared with 45% in controls
|
|
• leukocytosis, usually involving increases in granulocytes, in both pIpC and non-pIpC treated mice
|
|
• leukocytosis in mice injected with pIpC is mainly due to an increase in granulocyte population
|
|
• mice injected with pIpC show expansion of the red pulp by varying degrees of granulocytic
|
|
• 7 of 25 mice injected with pIpC develop thymic T cell lymphoblastic lymphomas
• 2 of 6 non pIpC treated mice show thymic lymphomas
|
|
• mice injected with pIpC develop moderate to severe splenomegaly
|
|
• 4-7 week old mice injected with pIpC develop a myeloproliferative disorder
• bone marrow of mice injected with pIpC shows myelomonocytic expansion
• all mice that are not treated with pIpC also develop a hematopoietic disease, however these mice exhibit expression of the mutant Kras, indicating that most likely endogenous IFN expression is sufficient to induce the cre transgene
• bone marrow cells from pIpC injected mice readily form colonies, predominately monocyte colony-forming units (M-CFUs) in a growth factor-independent manner unlike controls
|
|
• myeloproliferative phenotype
• myeloid hyperplasia of bone marrow
|
|
• leukocytosis, usually involving increases in granulocytes, in both pIpC and non-pIpC treated mice
|
|
• leukocytosis in mice injected with pIpC is mainly due to an increase in granulocyte population
|
|
• mice injected with pIpC show expansion of the red pulp by varying degrees of granulocytic
|
|
• 6 of 17 mice injected with pIpC develop nodal lymphoid hyperplasia
|
|
• perivascular and periportal infiltration in liver by myeloid and erythroid cells similar to what is seen in spleen
|
|
• ruffled fur
|
|
• 12 of 19 mice injected with pIpC develop squamous papillomas involving the anal and vulvo-vaginal skin and 8 of 22 mice develop squamous papillomas involving the ear
• 2 of 6 non-pIpC treated mice show ear squamous papillomas
|
|
• 8 of 22 mice injected with pIpC develop squamous papillomas involving the esophageal mucosa
|
|
• 7 of 25 mice injected with pIpC develop thymic T cell lymphoblastic lymphomas
• 2 of 6 non pIpC treated mice show thymic lymphomas
|
|
• 10 of 17 mice injected with pIpC exhibit multiple nodules in the lungs consisting of proliferating type II penumocytes
• 5 of 6 non pIpC treated mice show pulmonary adenomas
|
|
• 8 of 25 mice injected with pIpC develop squamous papillomas involving the oral mucosa
• 2 of 6 non-pIpC treated mice show oral squamous papillomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| juvenile myelomonocytic leukemia | DOID:0050458 |
OMIM:607785 |
J:88163 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mutants develop pancreatic ductal adenocarcinoma by 3 weeks of age
|
|
• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17
|
|
• severe
|
|
• all mutants develop pancreatic ductal adenocarcinoma by 3 weeks of age
|
|
• mutants exhibit acinar-to-ductal metaplasia
|
|
• mutants are moribound by weaning, with a median survival of about 17 days
|
|
• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17
|
|
• severe
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:164210 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival is on average 22 weeks
|
|
• mutants develop multiple visible subcutaneous tumors with 100% penetrance, starting from 4 months of age
• majority of tumors are located on the back and sides
|
|
• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor
|
|
• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months
• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas
|
|
• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor
|
|
• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months
• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant peripheral nerve sheath tumor | DOID:5940 | J:154673 | ||
| neurofibromatosis 1 | DOID:0111253 |
OMIM:162200 |
J:154673 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants show normal vascularization of the yolk sac and placental labyrinth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit reduced numbers of both adenomas and adenocarcinomas as compared to controls following intratracheal injection of Cre expressing adenovirus (Ad-Cre)
|
|
• mice exhibit lower tumor burden (% of lung area comprising tumors) as compared to controls following intratracheal injection of Ad-Cre
|
|
• mice exhibit reduced numbers of both adenomas and adenocarcinomas as compared to controls following intratracheal injection of Cre expressing adenovirus (Ad-Cre)
|
|
• mice exhibit lower tumor burden (% of lung area comprising tumors) as compared to controls following intratracheal injection of Ad-Cre
|
|
• mice exhibit reduced numbers of hyperplastic lesions as compared to controls following intratracheal injection of Ad-Cre
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bronchioles exhibit clusters of CCSP+SPC+ cells (indicators of BASCs) as early as 4 weeks of age that are not seen in controls
|
|
• mutants exhibit expansion of bronchioalveolar stem cells (BASCs) in terminal bronchi
• small bronchi exhibit clusters of CCSP+SPC+ cells (indicators of BASCs) as early as 4 weeks of age that are not seen in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in primary mouse embryonic fibroblasts treated with adenovirus-cre compared with wild-type cells although not as much as in cells heterozygous for Krastm4Tyj
|
|
• in mice infected with adenovirus cre
• however, mice do not exhibit increased lung tumor incidence compared with Krastm4Tyj heterozygotes
|
|
• in mice infected with adenovirus cre
• however, mice do not exhibit increased lung tumor incidence compared with Krastm4Tyj heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2-4 months following tamoxifen treatment, tumors develop in the face in 40% of treated mutants
|
|
• 100% of animals develop lip tumors 2-4 months after tamoxifen treatment
|
|
• 2-4 months following RU486 treatment, tumors develop in the back skin in 80% of treated mice
|
|
• tumors have hallmarks of benign papillomas with signs of squamous differentiation
• no animals develop invasive carcinoma within 4 months of tamoxifen treatment
|
|
• 2-4 months following tamoxifen treatment, tumors develop in the face in 40% of treated mutants
|
|
• 100% of animals develop lip tumors 2-4 months after tamoxifen treatment
|
|
• hyperplasia of the interfollicular epidermis in TAM treated mice
|
|
• after tamoxifen treatment, hyperthickening of the interfollicular epidermis (IFE) is observed, indicating that hyperproliferation of IFE cells and hyperplasia of the IFE results from Kras LSL-G12D activation
|
|
• 2-4 months following RU486 treatment, tumors develop in the back skin in 80% of treated mice
|
|
• tumors have hallmarks of benign papillomas with signs of squamous differentiation
• no animals develop invasive carcinoma within 4 months of tamoxifen treatment
|
|
• 2-4 months following tamoxifen treatment, tumors develop in the face in 40% of treated mutants
|
|
• 100% of animals develop lip tumors 2-4 months after tamoxifen treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lung adenocarcinomas cover 9% of lung area 9 weeks after administration of a Cre-recombinase expressing adenovirus
• tumor burden progresses from 9% of lung (6 weeks) to 28% at experimental endpoint (12+ weeks) in the presence of a Cre-recombinase expressing adenovirus
• Mapkap2 expressing tumors (MK2+) represent a higher proportion of tumor burden in relation to Mapkapk2 (MK2-) null tumors in the presence of a Cre-recombinase expressing adenovirus adenovirus
|
|
• lung adenocarcinomas cover 9% of lung area 9 weeks after administration of a Cre-recombinase expressing adenovirus
• tumor burden progresses from 9% of lung (6 weeks) to 28% at experimental endpoint (12+ weeks) in the presence of a Cre-recombinase expressing adenovirus
• Mapkap2 expressing tumors (MK2+) represent a higher proportion of tumor burden in relation to Mapkapk2 (MK2-) null tumors in the presence of a Cre-recombinase expressing adenovirus adenovirus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit reduced numbers of both adenomas and adenocarcinomas as compared to controls following intratracheal injection of Cre expressing adenovirus (Ad-Cre)
|
|
• mice exhibit lower tumor burden (% of lung area comprising tumors) as compared to controls following intratracheal injection of Ad-Cre
|
|
• mice exhibit reduced numbers of both adenomas and adenocarcinomas as compared to controls following intratracheal injection of Cre expressing adenovirus (Ad-Cre)
|
|
• mice exhibit lower tumor burden (% of lung area comprising tumors) as compared to controls following intratracheal injection of Ad-Cre
|
|
• mice exhibit reduced numbers of hyperplastic lesions as compared to controls following intratracheal injection of Ad-Cre
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lung tumor incidence in ad-cre infected mice is similar to Kras mutant mice wild-type for Plcl1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• following injection of a cre adenovirus in the ovarian bursa, all mice develop ovarian lesions consisting of endometrial glandular epithelium unlike un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
|
|
• following injection of a cre adenovirus in the ovarian bursa, mice with endometriosis also exhibit an increase in spleen and regional lymph nodes T regulatory cells compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
|
|
• following injection of a cre adenovirus in the ovarian bursa, mice exhibit an increase in the anti-MUC1 IgG response compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
|
|
• following injection of a cre adenovirus in the ovarian bursa, mice exhibit an increase in MUC1-specific IgM unlike un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice and similarly treated Tg(MUC1)79.24Gend mice
|
|
• following injection of a cre adenovirus in the ovarian bursa, T cells in the spleen and regional lymph nodes exhibit decreased IFN-gamma in response to polyclonal stimulation compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
|
|
• following injection of a cre adenovirus in the ovarian bursa, mice with endometriosis also exhibit an increase in spleen and regional lymph nodes T regulatory cells compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
|
|
• following injection of a cre adenovirus in the ovarian bursa, mice exhibit an increase in the anti-MUC1 IgG response compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice
|
|
• following injection of a cre adenovirus in the ovarian bursa, mice exhibit an increase in MUC1-specific IgM unlike un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice and similarly treated Tg(MUC1)79.24Gend mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• relative to mutant mice wild-type for Diras2
• incidence of pancreatic tumors is similar to mutant mice wild-type for both Diras2 and Ube2f but with fewer stage I and more stage II and III tumors
|
|
• relative to mutant mice wild-type for Diras2
• incidence of pancreatic tumors is similar to mutant mice wild-type for both Diras2 and Ube2f but with fewer stage I and more stage II and III tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected intramuscularly with an adenovirus expressing Cre recombinase into the extremities or into the uterus develop soft tissue sarcomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in a model of non-small cell lung carcinoma, mice exposed to a cre-expressing adenovirus exhibit fewer tumors and smaller tumor area compared with Krastm4Tyj/Kras+ Ralatm1.2Cjm/Rala+ Ralbtm1.1Cjm/Ralbtm1.2Cjm control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pIpC-induced mice die earlier than induced conditional Krastm1.1Khai mice
|
|
• mice induced with polyinosinic:polycytidylic acid (pIpC) develop a myelodysplastic syndrome/myeloproliferative neoplasm that is qualitatively similar to that seen in conditional Krastm1.1Khai mice, but with a faster onset
|
|
• dying pIpC-induced mice show splenomegaly
|
|
• expansion of immature myeloid cells in the bone marrow and spleen in pIpC-induced mice
|
|
• expansion of immature myeloid cells in the bone marrow of pIpC-induced mice
|
|
• dying pIpC-induced mice show splenomegaly
|
|
• dying pIpC-induced mice show splenomegaly
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop benign papillomas without progressing to malignancy following topical application of RU486 to the back of skin at 3 weeks of age for 5 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 24 weeks after intratracheal injection of Ad-Cre virus, mice tend to exhibit less advanced lung tumors with adenoma identified as the predominant tumor lesion
• only 11% of Ad-Cre-injected mice have lung adenocarcinomas as the predominant type of lesion; in comparison, 36% of single Krastm4Tyj heterozygotes have adenocarcinomas as the predominant lesion showing more advanced disease progression
|
|
• following intratracheal injection of Ad-Cre virus, the overall lung tumor burden is significantly lower than that in single Krastm4Tyj heterozygotes sacrificed at 24 weeks post-injection
|
|
• following intratracheal injection of Ad-Cre virus, the overall lung tumor burden is significantly lower than that in single Krastm4Tyj heterozygotes sacrificed at 24 weeks post-injection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bile duct hyperplasia is seen in some mice at 8 months of age
|
|
• bile duct dilation is seen in some mice at 8 months of age
|
|
• bile duct hyperplasia is seen in some mice at 8 months of age
|
|
• bile duct dilation is seen in some mice at 8 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice develop cholangiocarcinoma-like lesions composed of dysplastic dust-like structures surrounded by fibrosis within 2 months of birth
|
|
• all mice develop cholangiocarcinoma-like lesions composed of dysplastic dust-like structures surrounded by fibrosis within 2 months of birth
|
|
• all mice develop cholangiocarcinoma-like lesions composed of dysplastic dust-like structures surrounded by fibrosis within 2 months of birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• invasive ductal adenocarcinomas with extensive regional and distant metastases
|
|
• invasive ductal adenocarcinomas with extensive regional and distant metastases
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:187012 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice survive for a median of 84 days after pIpC injection
|
|
• increase in the number of proliferating splenocytes in pIpC treated mice; most of these proliferating cells are Mac1+/Gr1 lo or Ter119+
|
|
• spleens of pIpC-treated moribund mice are massively enlarged
(J:87429)
• in pIpC treated mice
(J:115071)
|
|
• mice treated with pIpC show large numbers of proliferating splenic Ter199+ cells, indicating that erythropoiesis is ineffective
(J:87429)
• the erythroid progenitor compartment is massively expanded in the spleen of pIpC treated mice
(J:115071)
• pIpC treated mice show normal numbers of early erythroid cells in the bone marrow but a paucity of all the more mature TER119 hi populations, indicating an inefficient transition from TER119- to TER119 hi stages of erythropoiesis
(J:115071)
• bone marrow from pIpC treated mice forms abnormally large BFU-E colonies characterized by both erythropoietin-independent growth and hypersensitivity to erythropoietin
(J:115071)
• spleen of pIpC treated mice contains increase of immature CD71 hi TER119-/lo cells and large numbers of TER119 hi erythroblasts
(J:115071)
|
|
• pIpC injected mice develop a myeloproliferative disease with excess monocytes
• bone marrow mononuclear cells from pIpC treated mice form significant numbers of colony-forming unit granulocyte-macrophage (CFU-GM) colonies in the absence of exogenous cytokines while wild-type cells do not
• CFU-GM shows an increased proliferative response without added cytokines (9-fold) or to GM-CSF (19-fold increase) or IL-3 (37-fold increase)
|
|
• mice show abundant myeloid cells at various stages of differentiation after pIpC injection
|
|
• pups injected with pIpC develop anemia
(J:87429)
• however, normal platelet counts are seen in pIpC injected mice
(J:87429)
|
|
• in pIpC treated mice
|
|
• in pIpC treated mice
|
|
• in pIpC treated mice
|
|
• pups injected with pIpC at 21 days of age develop progressive leukocytosis that is evident 3 weeks after pIpC injection
|
|
• mice show an expanded population of Mac-1+, Gr-1 lo cells, indicating an expansion of immature monocytic cells
|
|
• in pIpC treated mice
|
|
• increase in the number of proliferating splenocytes in pIpC treated mice; most of these proliferating cells are Mac1+/Gr1 lo or Ter119+
|
|
• spleens of pIpC-treated moribund mice are massively enlarged
(J:87429)
• in pIpC treated mice
(J:115071)
|
|
• pIpC injected mice develop a myeloproliferative disease with excess monocytes
• bone marrow mononuclear cells from pIpC treated mice form significant numbers of colony-forming unit granulocyte-macrophage (CFU-GM) colonies in the absence of exogenous cytokines while wild-type cells do not
• CFU-GM shows an increased proliferative response without added cytokines (9-fold) or to GM-CSF (19-fold increase) or IL-3 (37-fold increase)
|
|
• mice show abundant myeloid cells at various stages of differentiation after pIpC injection
|
|
• pups injected with pIpC at 21 days of age develop progressive leukocytosis that is evident 3 weeks after pIpC injection
|
|
• mice show an expanded population of Mac-1+, Gr-1 lo cells, indicating an expansion of immature monocytic cells
|
|
• pIpC injected mice show moderate hepatomegaly with myeloid infiltration, particularly in periportal areas
|
|
• increase in the number of proliferating splenocytes in pIpC treated mice; most of these proliferating cells are Mac1+/Gr1 lo or Ter119+
|
|
• serum erythropoietin levels are increased in proportion to anemia in pIpC treated mice
|
|
• pIpC injected mice show moderate hepatomegaly with myeloid infiltration, particularly in periportal areas
|
|
• spleens of pIpC-treated moribund mice are massively enlarged
(J:87429)
• in pIpC treated mice
(J:115071)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| NOT | acute myeloid leukemia | DOID:9119 |
OMIM:601626 |
J:87429 |
| juvenile myelomonocytic leukemia | DOID:0050458 |
OMIM:607785 |
J:115071 , J:87429 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike mice homozygous for Nf1tm1Par
and hemizygous for Tg(Fabp7-cre)2Gtm , mice are viable with no reduction in life span
|
| N |
• unlike mice homozygous for Nf1tm1Par
and hemizygous for Tg(Fabp7-cre)2Gtm no change in pyramidal neuron apical dendrite length or neuritic development are detected
|
|
• expansion of glial cells similar to that in mice homozygous for Nf1tm1Par
and hemizygous for Tg(Fabp7-cre)2Gtm
|
|
• increase in the number of GFAP+ astrocytes in the brain
|
|
• increase in the number of Olig2+ progenitor cells
|
|
• an increase in proliferating cells is seen in the CA2/3 region
|
| N |
(J:138868)
• unlike mice homozygous for Nf1tm1Par
and hemizygous for Tg(Fabp7-cre)2Gtm , no growth retardation is seen
(J:139866)
|
| N |
• unlike mice homozygous for Nf1tm1Par
and hemizygous for Tg(Fabp7-cre)2Gtm , no impairment in pituitary gland development is detected
|
|
• expansion of glial cells similar to that in mice homozygous for Nf1tm1Par
and hemizygous for Tg(Fabp7-cre)2Gtm
|
|
• increase in the number of GFAP+ astrocytes in the brain
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average cancer free survival is greater than 52 weeks and 2 of 9 mice develop pancreatic ductal adenocarcinoma
(J:116130)
• 2 of 11 mutants show evidence of pancreatic ductal adenocarcinoma at 6 months of age, but not at earlier times
(J:164210)
|
|
• pancreatic ductal lesions are seen at 9, 12, 18, and 26 weeks of are, similar to human pancreatic intraepithelial neoplasias (PanINs)
(J:87196)
• PanINs increase in number and size with age, however no invasive tumors are seen up to 30 weeks of age
(J:87196)
• no evidence of neoplasia in the acinar cell compartment, however focal reactive metaplastic changes are seen
(J:87196)
• low-grade mPanIN lesions are seen in 3 month old mutants and by 6 months of age, most mice exhibit mPanIN lesions
(J:164210)
|
|
• pancreatic islets are moderately enlarged but do not show evidence of neoplasia
|
|
• average cancer free survival is greater than 52 weeks and 2 of 9 mice develop pancreatic ductal adenocarcinoma
(J:116130)
• 2 of 11 mutants show evidence of pancreatic ductal adenocarcinoma at 6 months of age, but not at earlier times
(J:164210)
|
|
• pancreatic ductal lesions are seen at 9, 12, 18, and 26 weeks of are, similar to human pancreatic intraepithelial neoplasias (PanINs)
(J:87196)
• PanINs increase in number and size with age, however no invasive tumors are seen up to 30 weeks of age
(J:87196)
• no evidence of neoplasia in the acinar cell compartment, however focal reactive metaplastic changes are seen
(J:87196)
• low-grade mPanIN lesions are seen in 3 month old mutants and by 6 months of age, most mice exhibit mPanIN lesions
(J:164210)
|
|
• acinar-to-ductal metaplasia is seen at 1 week of age
|
|
• most mutants exhibit abdominal distention due to ascites fluid and pancreatic enlargement
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average tumor-free survival is 38 weeks
|
|
• 6 of 10 mice develop pancreatic ductal adenocarcinoma
|
|
• 6 of 10 mice develop pancreatic ductal adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 34.2 weeks
• 43% of tumors exhibit sarcomatoid differentiation
|
|
• 57% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
|
• 69% of tumors exhibit metastasis
|
|
• mutants develop pancreatic tumors with an average latency of 34.2 weeks
• 43% of tumors exhibit sarcomatoid differentiation
|
|
• 57% of tumors exhibit well differentiated ductal adenocarcinoma histology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 57 weeks
• 100% of tumors exhibit sarcomatoid carcinoma histology
|
|
• 67% of tumors exhibit metastasis
|
|
• mutants develop pancreatic tumors with an average latency of 57 weeks
• 100% of tumors exhibit sarcomatoid carcinoma histology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• complete penetrance of death due to invasive and metastic cancer by 11 weeks of age
(J:87196)
• average tumor-free survival is 8.6 weeks
(J:116130)
|
|
• solid pancreatic tumors, frequently adhering to adjacent organs and the retroperitoneum
(J:87196)
• tumors are highly invasive, frequently involving the duodenum, stomach, liver and/or spleen and occasionally obstructing the common bile duct
(J:87196)
• 26% of tumors exhibit anaplastic carcinoma histology
(J:108298)
• 26% of tumors exhibit sarcomatoid differentiation
(J:108298)
|
|
• tumors exhibit pathologic features of human pancreatic ductal adenocarcinomas
(J:87196)
• 48% of tumors exhibit well differentiated ductal adenocarcinoma histology
(J:108298)
• 6 of 6 mice develop pancreatic ductal adenocarcinoma
(J:116130)
|
|
• earlier onset (3-4 weeks of age) of local premalignant ductal lesions (pancreatic intraepithelial neoplasia) than in mice just expressing the oncogenic form KRAS2 and not deficient for Cdkn2a expression
• pancreatic ductal lesions progress rapidly to invasive pancreatic adenocarcinoma
|
|
• neoplasms frequently invade the lymphatic and vascular system, indicating metastatic invasion
(J:87196)
• 11% of tumors exhibit metastasis
(J:108298)
|
|
• neoplasms rapidly progressed to become invasive and metastatic tumors
|
|
• solid pancreatic tumors, frequently adhering to adjacent organs and the retroperitoneum
(J:87196)
• tumors are highly invasive, frequently involving the duodenum, stomach, liver and/or spleen and occasionally obstructing the common bile duct
(J:87196)
• 26% of tumors exhibit anaplastic carcinoma histology
(J:108298)
• 26% of tumors exhibit sarcomatoid differentiation
(J:108298)
|
|
• tumors exhibit pathologic features of human pancreatic ductal adenocarcinomas
(J:87196)
• 48% of tumors exhibit well differentiated ductal adenocarcinoma histology
(J:108298)
• 6 of 6 mice develop pancreatic ductal adenocarcinoma
(J:116130)
|
|
• earlier onset (3-4 weeks of age) of local premalignant ductal lesions (pancreatic intraepithelial neoplasia) than in mice just expressing the oncogenic form KRAS2 and not deficient for Cdkn2a expression
• pancreatic ductal lesions progress rapidly to invasive pancreatic adenocarcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:87196 , J:108298 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice develop oral tumors
|
|
• tamoxifen treated mice develop oral tumors
|
|
• tamoxifen treated mice develop oral tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice develop oral tumors; tumors grow faster than in single conditional Kras mutants
• oral tumors of tamoxifen treated mice are papillomas that express HPV-biomarkers p16 and MCM7
• 14 days after tamoxifen treatment, mice treated with rapamycin for 3 days exhibit a transient decrease in tumor growth with regrowth after rapamycin is removed
• 14 days after tamoxifen treatment, mice that are treated with image-guided radiotherapy show regression of tumors
|
|
• tamoxifen treated mice develop oral tumors; tumors grow faster than in single conditional Kras mutants
• oral tumors of tamoxifen treated mice are papillomas that express HPV-biomarkers p16 and MCM7
• 14 days after tamoxifen treatment, mice treated with rapamycin for 3 days exhibit a transient decrease in tumor growth with regrowth after rapamycin is removed
• 14 days after tamoxifen treatment, mice that are treated with image-guided radiotherapy show regression of tumors
|
|
• tamoxifen treated mice develop oral tumors; tumors grow faster than in single conditional Kras mutants
• oral tumors of tamoxifen treated mice are papillomas that express HPV-biomarkers p16 and MCM7
• 14 days after tamoxifen treatment, mice treated with rapamycin for 3 days exhibit a transient decrease in tumor growth with regrowth after rapamycin is removed
• 14 days after tamoxifen treatment, mice that are treated with image-guided radiotherapy show regression of tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| oral cavity cancer | DOID:8618 | J:210533 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop invasive intrahepatic cholangiocarcinoma with low penetrance (1 of 8 mutants) and long latency (at 36 weeks of age)
|
|
• mice develop liver tumors at 12 months of age and do not show obvious symptoms up to 18 months of age
• tumors resemble hepatocellular dysplasia
|
|
• mutants develop invasive intrahepatic cholangiocarcinoma with low penetrance (1 of 8 mutants) and long latency (at 36 weeks of age)
|
|
• mice develop liver tumors at 12 months of age and do not show obvious symptoms up to 18 months of age
• tumors resemble hepatocellular dysplasia
|
|
• mutants develop invasive intrahepatic cholangiocarcinoma with low penetrance (1 of 8 mutants) and long latency (at 36 weeks of age)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| intrahepatic cholangiocarcinoma | DOID:4928 | J:184949 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• lethality around 40 weeks of age
|
|
|
• mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks
|
|
|
• mice develop macrometastatic lesions in the lung and liver with 100% penetrance
|
|
|
• mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks
|
|
|
• mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:184935 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks
• marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature
|
|
|
• mice develop macrometastatic lesions in the lung and liver with 100% penetrance
|
|
|
• early lethality, with mice dying between around 10 and 30 weeks of age
|
|
|
• prostates show an expansion of the leukemia stem cell (LSC)high subpopulation of stem/progenitor cells
• both the LSChigh (basal cell population) and LSClow (luminal cell population) subpopulations show enhanced sphere-forming in vitro
|
|
|
• mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks
• marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature
|
|
|
• prostates show an expansion of the leukemia stem cell (LSC)high subpopulation of stem/progenitor cells
• both the LSChigh (basal cell population) and LSClow (luminal cell population) subpopulations show enhanced sphere-forming in vitro
|
|
|
• mice develop invasive carcinoma in both the dorsolateral and anterior lobes of the prostate as early as 4 weeks with poorly differentiated carcinoma by 10 weeks
• marker analysis indicates that prostatic epithelial cells undergo epithelial-to-mesenchymal transition and that tumors exhibit a human metastatic prostate cancer signature
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:184935 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• within 6 months, tamoxifen-treated mice develop large, rapid growing oligo-pigmented tumors with ulceration unlike wild-type mice
• tumors in tamoxifen-treated mice are largely composed of spindle cells with malignancy features
|
|
• within 2 to 3 months, tamoxifen-treated mice exhibit a darkening of the tails, ears, and paws compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• vasculature surrounding brain arteriovenous malformations is abnormal in tamoxifen-administered mice, with vessels appearing tortuous and dilated, similar to niduses associated with these lesions in human patients
|
|
• mice administered tamoxifen at P1 show presence of brain arteriovenous malformations at 8 weeks of age occurring in the cortex, just anterior to the cerebellum, as well as near the olfactory bulb
|
|
• mice administered tamoxifen at P1 only rarely show intracranial hemorrhage (1 of 28 mice) at 8 weeks of age
|
|
• vasculature surrounding brain arteriovenous malformations is abnormal in tamoxifen-administered mice, with vessels appearing tortuous and dilated, similar to niduses associated with these lesions in human patients
|
|
• mice administered tamoxifen at P1 only rarely show intracranial hemorrhage (1 of 28 mice) at 8 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| arteriovenous malformations of the brain | DOID:0060688 |
OMIM:108010 |
J:312482 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice develop melanomas with spindle-like morphology
|
|
• 8 of 11 (73%) mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology formation at a longer latency (median latency 24 weeks) than in Cdkn2atm2.1Nesh/Cdkn2atm2.1Nesh Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53tm1Brn Tg(Tyr-cre/ERT2)13Bos mice (median latency 14 weeks)
|
|
• tamoxifen-treated mice exhibit melanocyte proliferation unlike wild-type mice
|
|
• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
|
• median lifespan is approximately 70 days, with all mice dying around 120 days
|
|
• all mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:276349 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• survival is similar to mutant mice wild-type for Zdhhc20
|
|
• liver metastases are found in 40% of mice compared to 93% of mutant mice wild-type for Zdhhc20
• a similar trend is seen for lung metastases
• both total liver lesion area and number are profoundly reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in Krastm4Tyj/Kras+ Tg(Ipf1-cre)6Tuv Trp53tm1Thl/Trp53tm1Thlmice succumb to pancreatic tumors with an average latency of 65 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice succumb to pancreatic tumors with an average latency of 68 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 45 days compared with 68 days in Krastm4Tyj/Kras+ Tg(Ipf1-cre)6Tuv Trp53tm1Thl/Trp53tm1Thl
• however, latency is similar to in Brca1tm1Thl/Brca1tm1Thl Krastm4Tyj/Kras+ Tg(Ipf1-cre)6Tuv Trp53tm1Thl/Trp53tm1Thl
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• PanIN-1 and PanIN-2, but not PanIN-3 or pancreatic ductal adenocarcinoma, are seen at 22 weeks after birth
(J:214846)
• mice develop intraepithelial neoplasia (PanIN) by 8 weeks of age
(J:276349)
• mice show accelerated PanIN development when treated with cerulein to induce acute pancreatitis
(J:276349)
|
|
• mice develop a varying number of ductal cell proliferation foci in the pancreas from 9 weeks after birth
|
|
• mice develop a varying number of ductal cell proliferation foci in the pancreas from 9 weeks after birth
|
|
• PanIN-1 and PanIN-2, but not PanIN-3 or pancreatic ductal adenocarcinoma, are seen at 22 weeks after birth
(J:214846)
• mice develop intraepithelial neoplasia (PanIN) by 8 weeks of age
(J:276349)
• mice show accelerated PanIN development when treated with cerulein to induce acute pancreatitis
(J:276349)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice of this genotype (referred to as KPC mice, a model for pancreatic ductal adenocarcinoma) exhibit a median survival of 16 weeks; at 22 weeks, the overall survival rate is 0%
|
|
• in 2 mice
|
|
• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors
(J:98936)
• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes
(J:98936)
• mice exhibit the full spectrum of preinvasive lesions
(J:98936)
• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features
(J:98936)
|
|
• in young mice
|
|
• ACAA1 (acetyl-Coenzyme A acyltransferase 1A) protein levels are minimal in normal pancreatic tissue but increased 1.2-fold, 2.4-fold, and 2-fold during acinar-ductal epithelial degeneration (ADM), pancreatic intraepithelial neoplasia (PanIN), and pancreatic ductal adenocarcinoma (PDAC) stages, respectively, indicating a progressive increase during tumor development
• moreover, at the PDAC stage, ACOX1 (acyl-Coenzyme A oxidase 1, palmitoyl) protein expression is 5.92 times higher than in wild-type mice
|
|
• in one mouse
|
|
• some mice exhibit esophageal papillomas and hyperplasias or papillomatosis of the biliary tree unlike control mice
|
|
• in some mice
|
|
• KPC mice show a progressive increase in the expression of key proteins involved in fatty acid oxidation (FAO) within peroxisomes (ACAA1 and ACOX1) during PDAC development
|
|
• hemorrhagic
|
|
• in tumor cells
|
|
• KPC mice show a progressive increase in the expression of key proteins involved in fatty acid oxidation (FAO) within peroxisomes (ACAA1 and ACOX1) during PDAC development
|
|
• in some mice
|
|
• mice frequently exhibit small bowel obstructions unlike control mice
|
|
• in 2 mice
|
|
• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors
(J:98936)
• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes
(J:98936)
• mice exhibit the full spectrum of preinvasive lesions
(J:98936)
• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features
(J:98936)
|
|
• in young mice
|
|
• in 2 mice
|
|
• in 2 mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:98936 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 24 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
• average survival time is 168 days, with a range of 60-254 days
|
|
• 24 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a median survival of 19 weeks, that is 3 weeks longer than that of KPC mice alone (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 mice that are wild-type for Acaa1a)
• at 22 weeks, the survival rate is 34% versus 0% observed in KPC mice alone, indicating an improvement in the overall survival of KPC mice
|
|
• percentage of Ki-67 positive cells in pancreatic cancer tissue is significantly lower than that in KPC mice alone
|
|
• immunohistochemical staining for Ki-67 in pancreatic cancer tissue indicates that the Ki-67-positive area is reduced by 96% relative to KPC mice alone, consistent with suppressed tumor growth
|
|
• average H-score for LC3-II in pancreatic cancer tissue is 2.3 times higher than that in KPC mice alone, suggesting increased autophagy
|
|
• average H-score for LC3-II in pancreatic cancer tissue is 2.3 times higher than that in KPC mice alone, suggesting increased autophagy
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show colon epithelium crypt hyperplasia that is greater than seen in conditional Krastm1.1Khai mice
|
|
• Paneth cells are absent in colons
• mice treated with trametinib show restoration of Paneth cell differentiation in colons
|
|
• colons show a greater hyperproliferative phenotype than in conditional Krastm1.1Khai mice
|
|
• mice show colon epithelium crypt hyperplasia that is greater than seen in conditional Krastm1.1Khai mice
|
|
• Paneth cells are absent in colons
• mice treated with trametinib show restoration of Paneth cell differentiation in colons
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop colonic tumors, characterized as adenomas with low-grade dysplasia
|
|
• mice show 100% lethality before 150 days of age
|
|
• mice develop colonic tumors, characterized as adenomas with low-grade dysplasia
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:276349 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice intratracheally administered an adenovirus expressing cre recombinase (Ad-cre) develop lung tumor burden similar to single mutant Kras homozygous mice indicating rescue of the suppression of lung tumorigenesis by Ube2c
|
|
• mice intratracheally administered an adenovirus expressing cre recombinase (Ad-cre) develop lung tumor burden similar to single mutant Kras homozygous mice indicating rescue of the suppression of lung tumorigenesis by Ube2c
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• completely blocked in vitro proliferation of embryonic fibroblasts from mice treated with a cre-expressing adenovirus
|
|
• in 3-months-old mice after cre-expressing adenovirus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice intratracheally administered an adenovirus expressing cre recombinase (Ad-cre) show reduced lung tumor burden compared to single mutant Kras homozygous mice
|
|
• mice intratracheally administered Ad-cre have a median survival time of approximately 150 days and 100% death by 210 days compared to single mutant Kras homozygous mice which have a survival time of approximately 130 days with 100% death by 175 days, indicating increased survival
|
|
• mice intratracheally administered an adenovirus expressing cre recombinase (Ad-cre) show reduced lung tumor burden compared to single mutant Kras homozygous mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival of majority of mice is 10-20 weeks after intrabursal injection of an adenovirus expressing Cre
|
|
• 43% of ovarian tumors metastasize to the lungs
|
|
|
• 7 weeks after intrabursal injection through the infundibulum of an adenovirus expressing Cre, mice, mutants develop endometrioid ovarian cancer
• primary tumor is located in the ovary
• tumors are solid and cystic and diagnosed as ovarian edometrioid adenocarcinomas
|
|
|
• 7 weeks after intrabursal injection through the infundibulum of an adenovirus expressing Cre, mice, mutants develop endometrioid ovarian cancer
• primary tumor is located in the ovary
• tumors are solid and cystic and diagnosed as ovarian edometrioid adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:96296 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• more aggressive neoplastic progression with increased population of stage III neoplasia and decreased populations of acinar cells, acinar-to-ductal metaplasia, and stage I neoplasia compared to mutant mice wild-type for Diras2
|
|
• more aggressive neoplastic progression with increased population of stage III neoplasia and decreased populations of acinar cells, acinar-to-ductal metaplasia, and stage I neoplasia compared to mutant mice wild-type for Diras2
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• relative to mutant mice wild-type for Ube2f indicating improved growth
|
|
• decrease in pancreatic intraepithelial neoplasia at all 3 stages relative to mutant mice wild-type for Ube2f at 4, 6, and 9 months of age
• by 12 months of age there is an increase in stage I but decrease in stage II and III lesions in the pancreas indicating a delay in pancreatic tumor progression
|
|
• relative to mutant mice wild-type for Ube2f
|
|
• decrease in disruption of acinar cell population in cerulein-induced pancreatitis
• fewer infiltrations of leukocytes and neutrophils at 3d after cerulein treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in pIpC-treated mice but not as severe as when Chaf1b alleles are wild-type
|
| N |
• pIpC-treated mice exhibit normal numbers of red blood cells and platelets
|
|
• in pIpC-treated mice
|
|
• in pIpC-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2-4 months following RU486 treatment, tumors develop in the face in 35% of treated mutants
|
|
• 2-4 months following RU486 treatment, lip tumors develop in 57% of treated mice
|
|
• 2-4 months following RU486 treatment, tumors develop in the back skin in 14% of treated mice
|
|
• skin tumors are benign papillomas with no sign of malignant transformtion seen up to 4 months after treatment with RU486
• double mutants not treated with tamoxifen develop some papillomas but with increased latency (>6 months)
|
|
• 2-4 months following RU486 treatment, tumors develop in the back skin in 14% of treated mice
|
|
• skin tumors are benign papillomas with no sign of malignant transformtion seen up to 4 months after treatment with RU486
• double mutants not treated with tamoxifen develop some papillomas but with increased latency (>6 months)
|
|
• 2-4 months following RU486 treatment, tumors develop in the face in 35% of treated mutants
|
|
• 2-4 months following RU486 treatment, lip tumors develop in 57% of treated mice
|
|
• 2-4 months following RU486 treatment, tumors develop in the face in 35% of treated mutants
|
|
• 2-4 months following RU486 treatment, lip tumors develop in 57% of treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in pancreatic explants treated with 1NMPP1 and infected with a cre-expressing adenovirus without loss of intrinsic cell polarity
|
|
• in pancreatic explants treated with 1NMPP1 and infected with a cre-expressing adenovirus without loss of intrinsic cell polarity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice administered tamoxifen at P1 show lethality beginning at P12
• lethality is not due to failure to thrive
• however, mice treated with tamoxifen between 2 and 4 months of age show no effect on overall survival up to 8 weeks later and show no differences in viability up to 36 weeks later
|
|
• mice treated with tamoxifen at P1 show thin and fragile appearing cerebral vessels
• however, vessel density within the brain at P21 is normal
|
|
• more than 50% of mice treated with tamoxifen between 2 and 4 months develop brain arteriovenous malformations within 8 weeks of treatment
• however, mice treated with tamoxifen at P1 do not exhibit cortical brain arteriovenous malformations and cerebral vessels do not appear dilated
|
|
• mice administered tamoxifen at P1 that survive to P21 show an incompletely penetrant (11 of 32 mice) phenotype of focal intracranial hemorrhage
• however, mice treated with tamoxifen at P1 do not show hemorrhage in the intestines, lung, or liver at P14
• however, mice treated with tamoxifen between 2 and 4 months do not show hemorrhage 8 weeks after treatment
|
|
• mice treated with tamoxifen at P1 show thin and fragile appearing cerebral vessels
• however, vessel density within the brain at P21 is normal
|
|
• mice administered tamoxifen at P1 that survive to P21 show an incompletely penetrant (11 of 32 mice) phenotype of focal intracranial hemorrhage
• however, mice treated with tamoxifen at P1 do not show hemorrhage in the intestines, lung, or liver at P14
• however, mice treated with tamoxifen between 2 and 4 months do not show hemorrhage 8 weeks after treatment
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| arteriovenous malformations of the brain | DOID:0060688 |
OMIM:108010 |
J:312482 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• submandibular gland hyperplasia is seen in mutant mice
|
|
• submandibular gland hyperplasia is seen in mutant mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 1 in 14 tamoxifen treated mice develops melanoma with a median tumor latency greater than 52 weeks
|
|
• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice
|
|
• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• due to local or metastatic pancreatic cancer or aggressive oral papillomas
|
|
|
• aggressive oral papillomas
|
|
|
• within 3 months, mice develop pancreatic intraepithelial neoplasia and microinvasive neoplasms
|
|
|
• within 3 months
|
|
|
• in the face and urogenital area at 3 months
|
|
|
• in the face and urogenital area at 3 months
|
|
|
• within 3 months, mice develop pancreatic intraepithelial neoplasia and microinvasive neoplasms
|
|
|
• within 3 months
|
|
|
• aggressive oral papillomas
|
|
|
• aggressive oral papillomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:186717 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants aged up to 18 months do not develop skin papillomas, bladder tumors or lung tumors
(J:174242)
(J:234236)
|
| N |
• mice do not develop urothelium hyperplasia or bladder tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice succumb to pancreatic tumors with an average latency of 68 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• transitions of epithelium from cuboid to columnar as early as 2 weeks
• number and extent of lesions increases with age
• by 7-10 months occasional animals with invasive and metastatic adenocarcinomas
• lesions eventually found in liver diaphragm and lungs
|
|
• transitions of epithelium from cuboid to columnar as early as 2 weeks
• number and extent of lesions increases with age
• by 7-10 months occasional animals with invasive and metastatic adenocarcinomas
• lesions eventually found in liver diaphragm and lungs
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:87973 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• phenotypes are relative to the control KPC (KrasG12D/+, p53R172H/+, Pdx1-Cre) PDAC (pancreatic adenocarcinoma) model mice
• size of PDAC primary tumors same as control
|
|
• significantly reduced number of detectable PDAC metastases to liver, lung and other tissues
• reduced migration of PDAC cells in vitro
|
| N |
• survival same as control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• diffuse hyperplasia and dysplasia of the colonic crypts is seen by 4 weeks of age
• increased proliferation of the hyperplastic and dysplastic colonic epithelium is seen in mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• due to local or metastatic pancreatic cancer or aggressive oral papillomas
|
|
|
• aggressive oral papillomas
|
|
|
• within 3 months, mice develop pancreatic intraepithelial neoplasia and microinvasive neoplasms
|
|
|
• within 3 months
|
|
|
• in the face and urogenital area at 3 months
|
|
|
• in the face and urogenital area at 3 months
|
|
|
• within 3 months, mice develop pancreatic intraepithelial neoplasia and microinvasive neoplasms
|
|
|
• within 3 months
|
|
|
• aggressive oral papillomas
|
|
|
• aggressive oral papillomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:186717 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 42% of mutants develop skin papillomas
|
|
• 42% of mutants develop skin papillomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen treated mice do not exhibit thyroid size abnormalities or abnormal levels of TSH or T4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• well-differentiated adenocarcinomas in 13% of mice
|
|
|
• high-grade in 20% of mice
|
|
|
• increased cell proliferation and apoptosis compared to in Tg(Pbsn-cre)20Fwan mice
|
|
|
• well-differentiated adenocarcinomas in 13% of mice
|
|
|
• high-grade in 20% of mice
|
|
• focal intestinal metaplasia
|
|
|
• well-differentiated adenocarcinomas in 13% of mice
|
|
|
• high-grade in 20% of mice
|
|
|
• increased cell proliferation and apoptosis compared to in Tg(Pbsn-cre)20Fwan mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3 of 10 mice exhibit signs of illness and were sacrificed prior to 400 days
|
|
|
• well-differentiated adenocarcinomas in 20% of mice
|
|
|
• high-grade in 33% of mice
|
|
|
• increased cell proliferation and apoptosis compared to in Tg(Pbsn-cre)20Fwan mice
|
|
|
• high-grade in 33% of mice
|
|
• 3 of 15 mice develop poorly differentiated invasive carcinoma
|
|
|
• well-differentiated adenocarcinomas in 20% of mice
|
|
• focal intestinal metaplasia
|
|
|
• well-differentiated adenocarcinomas in 20% of mice
|
|
|
• high-grade in 33% of mice
|
|
|
• increased cell proliferation and apoptosis compared to in Tg(Pbsn-cre)20Fwan mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| prostate cancer | DOID:10283 |
OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959 |
J:178461 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• low-grade in 73% of mice
• high-grade in 18% of mice
|
|
|
• in 9% of mice
|
|
|
• increased cell proliferation and apoptosis compared to in Tg(Pbsn-cre)20Fwan mice
|
|
|
• in 9% of mice
|
|
• focal intestinal metaplasia
|
|
|
• low-grade in 73% of mice
• high-grade in 18% of mice
|
|
|
• in 9% of mice
|
|
|
• increased cell proliferation and apoptosis compared to in Tg(Pbsn-cre)20Fwan mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die 14 weeks or less after tamoxifen administration
|
|
• at 6-8 weeks of age, animals administered 1dose or 4 doses of tamoxifen develop widespread adenomas in the alveoli by 14 weeks of age, but the bronchoalveolar duct junction remains tumor-free
|
|
• at 6-8 weeks of age, animals administered 1dose or 4 doses of tamoxifen develop widespread adenocarcinomas in the alveoli by 14 weeks of age
|
|
• at 6-8 weeks of age, animals administered 1dose or 4 doses of tamoxifen develop widespread adenomas in the alveoli by 14 weeks of age, but the bronchoalveolar duct junction remains tumor-free
|
|
• at 2 weeks after tamoxifen treatement, brochioalveolar duct junctions (BADJ) appear normal, but small adenomas occur in the alveoli; these progress to adenocarcinoma but the BADJ remain histologically normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animal succumb due to tumor burden at 20-24 weeks
|
|
• at 6-8 weeks of age, animals administered 4 doses of tamoxifen develop adenomas in the alveoli by 15 weeks; these progress to adenocarcinomas
• papillary adenomas are seen in alveoli at 15 and 21 weeks after tamoxifen treatment
|
|
• develop in alveoli and near the bronchioalveolar duct junction by 15 weeks of age with tamoxifen administration at 6-8 weeks
• larger bronchioles and non terminal bronchi appear normal
• advanced papillary adenocarcinomas are observed at 21 weeks after tamoxifen treatment
|
|
• at 6-8 weeks of age, animals administered 4 doses of tamoxifen develop adenomas in the alveoli by 15 weeks; these progress to adenocarcinomas
• papillary adenomas are seen in alveoli at 15 and 21 weeks after tamoxifen treatment
|
|
• hyperplasia is observed at 3 weeks after tamoxifen induction, and persists at 15 and 21 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average tumor-free survival is 7.4 weeks
|
|
• 3 of 10 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
|
|
• 5 of 10 mice develop gastric cancer
|
|
• 9 of 10 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
|
|
• 5 of 10 mice develop gastric cancer
|
|
• 9 of 10 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average tumor-free survival is 12.6 weeks
|
|
• 4 of 12 mice develop intraductal papillary mucinous neoplasms
• tumor fibrosis is increased compared to mice wild-type for Smad4
|
|
• 8 of 12 mice develop gastric cancer
|
|
• 4 of 12 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
|
|
• 8 of 12 mice develop gastric cancer
|
|
• 4 of 12 mice develop pancreatic ductal adenocarcinoma
• the proportion of undifferentiated carcinomas is decreased compared to mice wild-type for Smad4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 5 of 8 mice develop gastric cancer with squamous or adenosquamous histology
|
|
• mice die between 8 and 24 weeks of age
• average tumor-free survival is 13.1 weeks
|
|
• seen in all mice
|
|
• seen in all mice
|
|
• 5 of 8 mice develop intraductal papillary mucinous neoplasms
|
|
• 5 of 8 mice develop gastric cancer with squamous or adenosquamous histology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 12 of 40 mutants develop pancreatic ductal adenocarcinomas
|
|
• reduction in pancreatic ductal adenocarcinoma-free survival
|
|
• 12 of 40 mutants develop pancreatic ductal adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 26 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
• average survival time is 143 days, with a range of 91-191 days
|
|
• 26 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• phenotypes are relative to the control KPC (KrasG12D/+, p53R172H/+, Pdx1-Cre) PDAC (pancreatic adenocarcinoma) model mice
• size of PDAC primary tumors same as control
|
|
• significantly reduced number of detectable PDAC metastases to liver, lung and other tissues
• reduced migration of PDAC cells in vitro
|
|
• survival reduced compared to control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice
|
|
• following adenovirus cre infection, mice exhibit increased lung tumor burden compared with control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when mice older than 6 weeks are given systemic tamoxifen treatment by intraperitoneal delivery, mice develop multiple tumors (avg. 3.9 per mouse) with 100% penetrance within 1-2 months; median tumor-free survival is 44 days
• tumors develop at various locations, including clinically relevant sites including the orbit
|
|
• tamoxifen treated mice develop tumors displaying a histological spectrum ranging from undifferentiated pleomorphic sarcoma (UPS) to rhabdomyosarcoma (RMS)
• tumors mimic embryonic RMS, pleomorphic RMS, or myogenic or nonmyogenic UPS
• sarcomas can appear in the body wall (37%), the extremities (31%), head and neck (23%), with some being subcutaneous (9%)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cre-activation leads to a rounded cell shape
• however, farnesylation of RHOA and CDC42 restores normal cell shape
|
|
• cre-activation leads to decreased cell proliferation
• however, farnesylation of RHOA and CDC42 restores proliferation induced by Krastm4Tyj
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice survive longer than Pggt1btm1Mbrg Lyzstm1(cre)Ifo Krastm4Tyj heterozygotes with some surviving until day 98 when they were euthanized
|
|
• few, very mild adenomatous hyperplasia are present at day 11 and increase in occurence by day 62
• however, many segments of the lung are normal at day 62
|
|
• at day 98, progressed and scattered adenomas are present
|
|
• lung weight is less than in Pggt1btm1Mbrg Lyzstm1(cre)Ifo Krastm4Tyj heterozygotes but higher than in normal mice
|
|
• few, very mild adenomatous hyperplasia are present at day 11 and increase in occurence by day 62
• however, many segments of the lung are normal at day 62
|
|
• at day 98, progressed and scattered adenomas are present
|
|
• after day 40, mice grow slower than controls
• however, up to day 40 mice grow normally
|
|
• lung weight is less than in Pggt1btm1Mbrg Lyzstm1(cre)Ifo Krastm4Tyj heterozygotes but higher than in normal mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are normal until day 17 when they begin to die or must be euthanized
median survival is to day 20
|
|
• tumors range from atypical adenomatous hyperplasia, adenoma and adenocarcinoma at day 11 to diffuse adenocarsinoma that obliterate alveolar space by day 20
|
|
• at day 11
|
|
• beginning at day 11 and obliterating alveolar space by day 20
|
|
• lung weight increases 10-fold between day 18 and 22
|
|
• tumors range from atypical adenomatous hyperplasia, adenoma and adenocarcinoma at day 11 to diffuse adenocarsinoma that obliterate alveolar space by day 20
|
|
• at day 11
|
|
• beginning at day 11 and obliterating alveolar space by day 20
|
|
• after day 17
|
|
• percentage of neutrophil is higher in peripheral blood than in controls
|
|
• percentage of lymphocytes is lower than in controls
|
|
• pools of immature myeloid are present in the spleen
|
|
• pools of immature myeloid are present in the spleen
• myeloid proliferation is increased
|
|
• percentage of neutrophil is higher in peripheral blood than in controls
|
|
• percentage of lymphocytes is lower than in controls
|
|
• pools of immature myeloid are present in the spleen
|
|
• myeloid infiltration of the liver occurs
|
|
• after day 17
|
|
• lung weight increases 10-fold between day 18 and 22
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with RU486 and TPA, mice develop more tumors than in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice
|
|
• following treatment with RU486 and TPA, conversion to malignant carcinoma is accelerated relative to in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice
|
|
• after RU486 and TPA treatment, 60% of tumors that develop are spindle cell carcinomas
|
|
• following treatment with RU486 and TPA, mice develop more tumors than in Krastm4Tyj Trp53tm1Brn/ Trp53tm1Brn Tg(KRT5-cre/PGR)1Der mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after RU486 and TPA treatment, 30% of mice develop skin carcinomas compared to 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following treatment with RU486 and TPA, mice develop less tumors than in Krastm4Tyj Trp53tm1Brn/Trp53tm3Glo Tg(KRT5-cre/PGR)1Der mice
|
|
• after RU486 and TPA treatment, carcinomas that develop following treatment with RU486 and TPA are squamous cell carcinomas with abundant keratin pearls and an absence of spindle cells
|
|
• following treatment with RU486 and TPA, mice develop less tumors than in Krastm4Tyj Trp53tm1Brn/Trp53tm3Glo Tg(KRT5-cre/PGR)1Der mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% survival at 46.3 weeks of age is seen following intratracheal instillation of Ad-Cre, a 20% increase in survival compared to single Kras mutants
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mutants show 50% survival at 63 weeks versus 48 weeks in single Kras mutants, a 40% increase in survival
|
|
• 6 months following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), only a few tumors are observed; tumors that are found express normal levels of Mapk1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Ad-Cre treated mutants show 50% survival at 52 weeks compared to 45 weeks in single Kras heterozygous controls, indicating a slight 19% increase in survival
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Ad-Cre treated mice show 50% survival at 57 weeks of age compared to 33 weeks of age in single Kras heterozygous controls, indicating an almost 100% increase in survival
|
|
• 6 months following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), only a few tumors are observed; tumors that are present carry unrecombined Map2k1 alleles and express normal levels of Map2k1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a median survival of 22 weeks after ad-cre inoculation
|
|
• mice inoculated with ad-cre by inhalation develop lung adenocarcinomas with high multiplicity, however metastasis is not observed
|
|
• mice inoculated with ad-cre by inhalation develop lung adenocarcinomas with high multiplicity, however metastasis is not observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• death in the early postnatal period
|
|
• with doxycycline treatment beginning at E6.5, a dramatic lung branching defect is observed
• at E16.5, lungs show even more severe defects than in Kras:Meox2-cre embryos, with large epithelial-lined pouches in place of finely branched network of airways seen in wild-type
• branching defect persists through late gestation leading to early postnatal lethality
|
|
• branching defect originates in epithelium rather than mesenchyme
|
|
• markers of ciliated and Clara cells in the bronchi are significantly reduced at E18.5 compared to controls, indicating block in differentiation of lung epithelium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after RU486 and TPA treatment, mice develop three-fold more tumors than Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
|
|
• after RU486 and TPA treatment, 60% of mice develop metastasis in the lungs and/or lymph nodes compared to no wild-type mice
|
|
• after RU486 and TPA treatment, 42% of tumors exhibit aneuplody compared to 23% of Krastm4Tyj Trp53tm1Brn heterozygotes and 20% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, tumors exhibit centrosome amplification in 3% to 5% of tumors cells
|
|
• after RU486 and TPA treatment, carcinoma development is accelerated compared to in Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, 90% of mice develop skin carcinomas compared to 30% of Krastm4Tyj Trp53tm1Brn heterozygotes and 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
|
|
• after RU486 and TPA treatment, tumors exhibit centrosome amplification in 3% to 5% of tumors cells
|
|
• after RU486 and TPA treatment, mice develop three-fold more tumors than Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 7 to 10 weeks after treatment with RU486 to activate the cre transgene, mice develop epidermal papillomas
|
|
• 7 to 10 weeks after treatment with RU486 to activate the cre transgene, mice develop epidermal papillomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced pancreatic intraepithelial neoplasia incidence and tumor size compared with Krasem1Gpt/ Kras+ Tg(Pdx1-cre)89.1Dam mice
|
|
• reduced pancreatic intraepithelial neoplasia incidence and tumor size compared with Krasem1Gpt/ Kras+ Tg(Pdx1-cre)89.1Dam mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced pancreatic intraepithelial neoplasia incidence at both 6 and 9 months of age compared with Krasem1Gpt/ Kras+ Tg(Pdx1-cre)89.1Dam mice
|
|
• reduced pancreatic intraepithelial neoplasia incidence at both 6 and 9 months of age compared with Krasem1Gpt/ Kras+ Tg(Pdx1-cre)89.1Dam mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 19 of 26 mice develop chylous ascites unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• do not survive to weaning
|
|
• most deaths occur between E18.5 and birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• smaller tumors of mice treated with piperlongumine than in Krastm3Tyj heterozygotes
|
|
• fewer tumors by 12 weeks with a more than 2-fold reduction in tumor burden compared with Krastm3Tyj heterozygotes
|
|
• in tumors of mice treated with piperlongumine
|
|
• increased compared with Krastm3Tyj heterozygotes
|
|
• fewer tumors by 12 weeks with a more than 2-fold reduction in tumor burden compared with Krastm3Tyj heterozygotes
|
|
• in tumors of mice treated with piperlongumine
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average lifespan is 266 days with female mice exhibiting shorter lifespans than male mice
|
|
• lung adenocarcinomas and mesothelioma are highly invasive and metastatic with metastatic lesions observed in the lymph nodes and liver
• 19 of 52 mice with lung adenocarcinomas exhibit metastasis compared to only 2 of 44 Krastm2Tyj heterozygotes
|
|
• 81.8% of mice with end-stage lung adenocarcinomas exhibit loss of heterozygosity of the Trp53 wild-type allele
|
|
• mice develop adenocarcinomas, adenomas, lymphomas, mesotheliomas, angiosarcomas, fibrosarcomas, pancreatic carcinomas, squamous carcinomas, and papillomas
|
|
• 52 of 56 mice develop atypical adenamatous hyperplasia, adenomas and adenocarcinomas
• most mice develop multiple large or diffuse adenocarcinomas that have glandular phenotypes or are poorly differentiated
|
|
• some mice develop lung lymphomas
|
|
• 13 of 56 mice develop mesothelioma 6 of which are peritoneal mesotheliomas
|
|
• 52 of 56 mice develop atypical adenamatous hyperplasia, adenomas and adenocarcinomas
• most mice develop multiple large or diffuse adenocarcinomas that have glandular phenotypes or are poorly differentiated
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:129627 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival time of double mutants is 41 weeks compared to 55 weeks for KrasLA+/-, Dmtf1-sufficient mice
|
|
• one case of cholangiocarcinoma was observed
|
|
• ~30% of mice develop thymic lymphomas
|
|
• 20-30% of animals develop tail papillomas
|
|
• <5% of animals show distant metastases (liver/intr-abdominal or leg) of lung tumors, while no metastases are observed in KrasLA+/-, Dmtf1-sufficient mice
|
|
• one case of neurofibroma was observed
|
|
• one case of osteosarcoma was observed
|
|
• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion
|
|
• all mice develop lung adenomas or lung adenocarcinomas
|
|
• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in KrasLA+/- single mutants
• number of tumor nodules increase as animals become sick, with trend to increased nodule size
|
|
• tumorigenesis is accelerated relative to heterozygous Kras, wild-type Dmtf1 mice
|
|
• 20-30% of animals develop tail papillomas
|
|
• one case of cholangiocarcinoma was observed
|
|
• ~30% of mice develop thymic lymphomas
|
|
• one case of cholangiocarcinoma was observed
|
|
• one case of osteosarcoma was observed
|
|
• one case of neurofibroma was observed
|
|
• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion
|
|
• all mice develop lung adenomas or lung adenocarcinomas
|
|
• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in KrasLA+/- single mutants
• number of tumor nodules increase as animals become sick, with trend to increased nodule size
|
|
• ~30% of mice develop thymic lymphomas
|
|
• ~30% of mice develop thymic lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival time of double mutants is 36 weeks compared to 55 weeks for Kras+/-, Dmtf1-sufficient mice
|
|
• ~20% of mice develop thymic lymphomas
|
|
|
• one case of ovarian cystic adenoma was observed
|
|
• 30-40% of animals develop tail papillomas
|
|
• <5% of animals show distant metastases (liver/intr-abdominal or leg) of lung tumors, while no metastases are observed in KrasLA+/-, Dmtf1-sufficient mice
|
|
• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion
|
|
• all mice develop lung adenomas or lung adenocarcinomas
|
|
• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in KrasLA+/- single mutants
• number of tumor nodules increase as animals become sick, with trend to increased nodule size
|
|
• tumorigenesis is accelerated relative to heterozygous Kras, wild-type Dmtf1 mice
|
|
• 30-40% of animals develop tail papillomas
|
|
• ~20% of mice develop thymic lymphomas
|
|
|
• one case of ovarian cystic adenoma was observed
|
|
|
• one case of ovarian cystic adenoma was observed
|
|
• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion
|
|
• all mice develop lung adenomas or lung adenocarcinomas
|
|
• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in KrasLA+/- single mutants
• number of tumor nodules increase as animals become sick, with trend to increased nodule size
|
|
• ~20% of mice develop thymic lymphomas
|
|
• ~20% of mice develop thymic lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice have reduced life spans compared to Kras or Trp53 heterozygous mice, or Trp53 homozygotes
|
|
• double mutants display more malignant features than Kras heterozygous tumors, with marked cellular pleomorphism and anaplastic changes with giant cell formation
• mice have broader tumor spectrum compared to Kras or Trp53 heterozygotes, including histocytic sarcoma, medulloblastoma, osteosarcoma, and teratoma
|
|
• Background Sensitivity: about 40% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background
|
|
• about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background
|
|
• about 30% of double mutants develop fibrosarcoma
|
|
• about 30% of double mutants develop hemangiosarcoma
|
|
• about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background
|
|
• Background Sensitivity: about 40% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background
|
|
• Background Sensitivity: about 40% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background
|
|
• Background Sensitivity: about 40% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants display more malignant features than Kras heterozygous tumors, with marked cellular pleomorphism and anaplastic changes with giant cell formation
• mice have broader tumor spectrum compared to Kras or Trp53 heterozygotes, including histocytic sarcoma, medulloblastoma, osteosarcoma, and teratoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• zero to two visible tumors are found compared to forty or so tumors in Krastm3Tyj mice
• apoptotic rates in small lesions are increased compared to in Krastm3Tyj mice
|
|
• one mouse did not show any evidence of lung tumor formation up to 6 months of age
|
|
• one mouse did not show any evidence of lung tumor formation up to 6 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit premature death compared with wild-type mice
• however, mice exhibit the same mortality as Krastm3Tyj heterozygotes
|
|
• increased proliferation of tumor cells compared with tumor cells from Krastm3Tyj heterozygotes
|
|
• at 18 weeks compared with Krastm3Tyj heterozygotes
• mice develop increased incidence of all tumor grades without increasing the rate of conversion to adenocarcinoma compared with Krastm3Tyj heterozygotes
|
|
• of thymic tumors compared with Krastm3Tyj heterozygotes
|
|
• at 18 weeks compared with Krastm3Tyj heterozygotes
• mice develop increased incidence of all tumor grades without increasing the rate of conversion to adenocarcinoma compared with Krastm3Tyj heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival time of double mutants is 21 weeks compared to 35 weeks for Kras+/-, Dmtf1-sufficient mice
|
|
• ~20% of mice develop thymic lymphomas
|
|
• 10-20% of animals develop tail papillomas
|
|
• all mice develop lung adenomas or lung adenocarcinomas
|
|
• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in KrasLA+/- single mutants
• number of tumor nodules increase as animals become sick, with trend to increased nodule size
|
|
• tumorigenesis is accelerated relative to heterozygous Kras, wild-type Dmtf1 mice
|
|
• 10-20% of animals develop tail papillomas
|
|
• ~20% of mice develop thymic lymphomas
|
|
• all mice develop lung adenomas or lung adenocarcinomas
|
|
• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in KrasLA+/- single mutants
• number of tumor nodules increase as animals become sick, with trend to increased nodule size
|
|
• ~20% of mice develop thymic lymphomas
|
|
• ~20% of mice develop thymic lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival time of double mutants is 21 weeks compared to 35 weeks for Kras+/-, Dmtf1-sufficient mice
|
|
• ~35% of mice develop thymic lymphomas
|
|
• 10-20% of animals develop tail papillomas
|
|
• <5% of animals show distant metastases (liver/intr-abdominal or leg) of lung tumors, while no metastases are observed in KrasLA+/-, Dmtf1-sufficient mice
|
|
• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion
|
|
• all mice develop lung adenomas or lung adenocarcinomas
|
|
• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in KrasLA+/- single mutants
• number of tumor nodules increase as animals become sick, with trend to increased nodule size
|
|
• tumorigenesis is accelerated relative to heterozygous Kras, wild-type Dmtf1 mice
|
|
• 10-20% of animals develop tail papillomas
|
|
• ~35% of mice develop thymic lymphomas
|
|
• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion
|
|
• all mice develop lung adenomas or lung adenocarcinomas
|
|
• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in KrasLA+/- single mutants
• number of tumor nodules increase as animals become sick, with trend to increased nodule size
|
|
• ~35% of mice develop thymic lymphomas
|
|
• ~35% of mice develop thymic lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 60% reduction of number of tumor nodes at age 12 weeks
• 54% reduction in tumor area at age 12 weeks
|
|
• 60% reduction of number of tumor nodes at age 12 weeks
• 54% reduction in tumor area at age 12 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike Krastm3Tyj heterozygotes, mice do not develop skin papillomas or lung adenomcarcinomas
|
|
• fewer than in Krastm3Tyj heterozygotes
|
|
• mice exhibit decreased total tumor area relative to lung area compared with Krastm3Tyj heterozygotes
• however, tumor cell proliferation is the same as in Krastm3Tyj heterozygotes
|
|
• mice develop fewer lung adenoma than in Krastm3Tyj heterozygotes
|
|
• mice develop fewer thymic lymphoma, lung hyperplasia and lung adenomas than in Krastm3Tyj heterozygotes
|
|
• fewer lung adenoma than in Krastm3Tyj heterozygotes
|
|
• mice develop fewer lung adenoma than in Krastm3Tyj heterozygotes
|
|
• fewer lung adenoma than in Krastm3Tyj heterozygotes
|
|
• mice develop fewer lung hyperplasia than in Krastm3Tyj heterozygotes
|
|
• fewer than in Krastm3Tyj heterozygotes
|
|
• fewer than in Krastm3Tyj heterozygotes
|
|
• fewer than in Krastm3Tyj heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 1 of 13 mice develop chylous ascites unlike wild-type mice
|
|
• a few mice exhibit lymphatic vessel hypoplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no mice exhibit chylous ascites
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no mice exhibit chylous ascites
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• intestinal
|
|
• all mice develop chylous ascites unlike wild-type mice
|
|
• mice develop lymphatic vessel hypoplasia unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 6 of 6 mice develop chylous ascites unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 35 of 37 mice develop chylous ascites unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 20 of 135 mice develop chylous ascites unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 5 of 76 mice develop chylous ascites unlike wild-type mice
|
|
• in the small intestine
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a few mutant embryos survive up to P2, but are subsequently neglected by their mothers and die shortly thereafter
|
|
• ~30% of these mutants die perinatally
|
|
• ~70% of these mutants die between E10.0 and E12.0
|
|
• at E10.5, mutant embryos display dilated pericardial sacs
|
|
• at E10.5, mutant embryos exhibit a dilated heart
|
|
• by E10.5, cell death extends throughout the entire embryo
|
|
• at E10.5, mutant embryos appear to have arrested at ~E9.5
• ~30% of abnormal mutant embryos survive beyond this early developmental block but are readily identifiable up until the final stages of gestation
|
|
• by E10.5, 65% of viable mutant embryos appear grossly abnormal
• starting at E9.5, ~50% of mutants are delayed by 0.5-1.0 developmental days, but never show the non-coordinate delay observed in late Krastm1Tyj embryos
|
|
• at E10.5, mutant embryos display a near or complete absence of blood islands in yolk sacs
|
|
• at E10.5, mutant yolk sacs appear rough and wrinkled
|
|
• at E10.5, mutant embryos exhibit significantly reduced numbers of circulating primitive erythrocytes in either the yolk sac or the embryo
|
|
• at E15.5, viable mutant embryos are developmentally delayed and severely edematous
|
|
• at E9.5, mutant embryos display prominent cell death in the forebrain, and to a lesser extent along the neural axis
|
|
• by E10.5, cell death extends throughout the entire embryo
|
|
• at E10.5, mutant embryos exhibit significantly reduced numbers of circulating primitive erythrocytes in either the yolk sac or the embryo
|
|
• at E15.5-16.5, mutant fetal livers display a significantly reduced ratio in the number of erythroblasts to hepatocytes
|
|
• at E15.5, viable mutant embryos are developmentally delayed and severely anemic
• anemia appears to be attributable to inadequate, but apparently normal, production of definitive erythrocytes and may reflect a defect in the survival or differentiation of either the erythroblasts or a more primitive progenitor cells
|
|
• 22% of E13.5-18.5 mutant embryos display an asymmetrical pattern in eye development, involving only the right eye
• either the right eye is significantly smaller than its wild-type counterpart or the pigment of the eye is overgrown
|
|
• 20% of E13.5-18.5 mutant embryos exhibit severe shortening of the tail
|
|
• by 16.5, a high % of mutant hepatocytes appear extremely vacuolated in the absence of increased cell death
|
|
• by E10.5, 65% of viable mutant embryos appear grossly abnormal
• starting at E9.5, ~50% of mutants are delayed by 0.5-1.0 developmental days, but never show the non-coordinate delay observed in late Krastm1Tyj embryos
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 12/30/2025 MGI 6.24 |
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