|
Allele Symbol Allele Name Allele ID |
Trp53tm1Brn targeted mutation 1, Anton Berns MGI:1931011 |
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| Summary |
227 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• ovarian surface epithelium (OSE) cells do not show any enhancement of proliferation after adenoviral cre treatment
|
|
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit increased cell motility and invasion compared with cells transfected with a lacZ-expressing adenovirus
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• after adenoviral cre infection, OSE cells in culture show significantly higher sensitivity to cisplatin treatment compared to control cells (31% remain ater 48 hours compared to 40% of control cells remaining)
|
|
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit increased cell motility compared with cells transfected with a lacZ-expressing adenovirus
|
| N |
• mice do not develop mesothelioma following injection of adenovirus expressing Cre into the bladder or intraperitoneally at 2-3 months of age
|
|
• in 6 of 7 mice treated with a cre-expressing adenovirus
(J:86077)
• in 6 of 7 mice following treatment with cre-expressing adenovirus
(J:157319)
|
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• ovarian surface epithelium cells with a cre-expressing adenovirus exhibit enhanced wound closure compared with cells transfected with a lacZ-expressing adenovirus
|
|
• in 6 of 7 mice treated with a cre-expressing adenovirus
(J:86077)
• in 6 of 7 mice following treatment with cre-expressing adenovirus
(J:157319)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• 2 of 7 mice injected with an adenovirus expressing cre recombinase into the bursa develop bursal cysts 6 months after injection
• however, mice injected with an adenovirus expressing cre recombinase into the oviduct exhibit no change in phenotype 3 months after injection
|
|
|
• 2 of 7 mice injected with an adenovirus expressing cre recombinase into the bursa exhibit ovary degeneration 6 months after injection
|
|
|
• 2 of 7 mice injected with an adenovirus expressing cre recombinase into the bursa develop bursal cysts 6 months after injection
• however, mice injected with an adenovirus expressing cre recombinase into the oviduct exhibit no change in phenotype 3 months after injection
|
|
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• 2 of 7 mice injected with an adenovirus expressing cre recombinase into the bursa exhibit ovary degeneration 6 months after injection
|
|
|
• 2 of 7 mice injected with an adenovirus expressing cre recombinase into the bursa develop bursal cysts 6 months after injection
• however, mice injected with an adenovirus expressing cre recombinase into the oviduct exhibit no change in phenotype 3 months after injection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in all mice treated with a cre-expressing adenovirus
(J:86077)
• in 6 of 7 mice following treatment with cre-expressing adenovirus
(J:157319)
|
|
• in all mice treated with a cre-expressing adenovirus
(J:86077)
• in 6 of 7 mice following treatment with cre-expressing adenovirus
(J:157319)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit increased invasion compared with control cells that is not as severe as in similarly treated cells from Trp53tm1Brn homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 38.4 weeks
|
|
• 4-8 week old mice only show areas of well differentiated follicular carcinomas but go on to develop well-differentiated follicular carcinomas by 8-10 months of age exhibiting spindle cell morphology, giant, osteoclast-like, multinucleated cells and areas of osseous metaplasia resembling human thyroid anaplastic carcinomas
• anaplastic thyroid carcinomas undergo dedifferentiation, genomic instability and epithelial-to-mesenchymal transition and exhibit a shift from an oxidative to a glycolytic pathway
|
|
• aggressive tumors invade locally into the muscle and trachea and metastasize to the lungs in 28% of mice, or less often, to the liver
|
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• all 8-10 month old mice exhibit enlarged thyroid gland causing severe tracheal compression
|
|
• 4-8 week old mice only show areas of well differentiated follicular carcinomas but go on to develop well-differentiated follicular carcinomas by 8-10 months of age exhibiting spindle cell morphology, giant, osteoclast-like, multinucleated cells and areas of osseous metaplasia resembling human thyroid anaplastic carcinomas
• anaplastic thyroid carcinomas undergo dedifferentiation, genomic instability and epithelial-to-mesenchymal transition and exhibit a shift from an oxidative to a glycolytic pathway
|
|
• reduction in TSH serum levels
• however, T4 levels are normal
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| thyroid gland carcinoma | DOID:3963 | J:211100 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in Rb1tm2Brn/Rb1tm2Brn Trp53tm1Brn/Trp53tm1Brn Tg(Gfap-cre)2Brn mice
|
|
• large cell carcinoma
|
|
• as in Rb1tm2Brn/Rb1tm2Brn Trp53tm1Brn/Trp53tm1Brn Tg(Gfap-cre)2Brn mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• spontaneous development of malignant melanoma by 200 days of age in all mice treated with tamoxifen
• tumors of tamoxifen-treated mice are relatively small, with regular ovoid shape and high levels of Ki-67 staining
• naevi are not seen above dermal malignant melanomas in tamoxifen treated mice, although small nests of melanocytes in a subepidermal location are occasionally seen
• early lesions of tamoxifen treated mice do not show evidence of tumor derivation from the upper dermis and appear to be derived from follicular or other deep dermal precursors
• majority of tumors of tamoxifen treated mice are located on the back
|
|
• all mice treated with tamoxifen develop malignant melanoma before 150 days of age after a single neonatal UVB dose
• tamoxifen-treated mice show a diminished response of melanocyte emigration from the upper regions of hair follicles to the epidermal basal layer 3-5 days after neonatal UV radiation compared to controls
|
|
• majority of tumors of tamoxifen treated mice are located on the back
• spontaneous development of malignant melanoma by 200 days of age in all mice treated with tamoxifen
• tumors of tamoxifen-treated mice are relatively small, with regular ovoid shape and high levels of Ki-67 staining
• naevi are not seen above dermal malignant melanomas in tamoxifen treated mice, although small nests of melanocytes in a subepidermal location are occasionally seen
• early lesions of tamoxifen treated mice do not show evidence of tumor derivation from the upper dermis and appear to be derived from follicular or other deep dermal precursors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 15 of 17 mice develop mammary neoplasms
• mammary tumor cells exhibit increased genomic instability compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice
|
|
• cell proliferation in mammary carcinomas is increased compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice
|
|
• 10 of 43 neoplasms are well-differentiated carcinomas
• while one tumor is an adenosquamous carcinoma the remaining tumors are poorly differentiated carcinomas with spindle or polygonal, frequently pleomorphic cells
|
|
• 1 adenosquamous carcinoma
|
|
• 4 of 40 mice develop lung metastasis
|
|
• mammary tumor cells exhibit increased genomic instability compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice
|
|
• 15 of 17 mice develop mammary neoplasms
• mammary tumor cells exhibit increased genomic instability compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice
|
|
• 15 of 17 mice develop mammary neoplasms
• mammary tumor cells exhibit increased genomic instability compared to in Trp53tm1Brn/Trp53tm1Brn Tg(MMTV-cre)105Ayn mice
|
|
• 4 of 40 mice develop lung metastasis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 700 days, 8 of 16 mice develop mammary neoplasms
• however, mice do not exhibit lymphomas or other non-mammary neoplasms
|
|
• 8 of 27 neoplasms are well-differentiated carcinomas
• while one tumor is an adenosquamous carcinoma the remaining tumors are poorly differentiated carcinomas with spindle or polygonal, frequently pleomorphic cells
|
|
• 1 adenosquamous carcinoma
|
|
• 3 of 27 mice develop lung metastasis
|
|
• by 700 days, 8 of 16 mice develop mammary neoplasms
• however, mice do not exhibit lymphomas or other non-mammary neoplasms
|
|
• 3 of 27 mice develop lung metastasis
|
|
• by 700 days, 8 of 16 mice develop mammary neoplasms
• however, mice do not exhibit lymphomas or other non-mammary neoplasms
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreatic tumors and liver metastasis express high levels of glucagon and mice exhibit increased circulating glucagon levels indicating that tumors are glucagonoma
|
|
• mice develop pancreatic neuroendocrine tumors that are classified as metastatic islet cell carcinoma; tumors are nodular and highly vascularized
• marker analysis indicates that both the primary pancreatic tumor and the liver metastases are pancreatic neuroendocrine in origin
|
|
• metastasis to the liver and lymph node is seen; liver metastases are nodular and highly vascularized
• liver also contains many separate metastatic foci
|
|
• mice develop subcutaneous tumors infrequently at around 3-4 months of age; these tumors have a solid growth pattern and are consistent with high-grade vascular sarcoma
|
|
• pancreatic tumors and liver metastasis express high levels of glucagon and mice exhibit increased circulating glucagon levels indicating that tumors are glucagonoma
|
|
• mice develop pancreatic neuroendocrine tumors that are classified as metastatic islet cell carcinoma; tumors are nodular and highly vascularized
• marker analysis indicates that both the primary pancreatic tumor and the liver metastases are pancreatic neuroendocrine in origin
|
|
• primary mortality is from metastatic pancreatic neuroendocrine disease with lethal onset beginning at around 22 weeks of age
• in rare instances, mice develop subcutaneous tumors and need to be euthanized at around 12-16 weeks of age and in even more rare cases, mice die as early as 8 weeks of age of unknown causes; these cases constitute about 12% of mice
|
|
• mice show increased circulating glucagon levels at 4, 5 and 6 months but not at 2 months of age
|
|
• 32% reduction in body weight of sick mutants
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| adenoma | DOID:657 | J:216559 | ||
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:216559 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice survive to around 13.9 weeks
• treatment of mice with RANK-Fc prolongs survival to around 17.8 weeks
|
|
• mice develop osteosarcoma within 10.3 weeks of age
• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels
• treatment of mice with RANK-Fc for 52 weeks beginning at 12.6 weeks of age keeps mice tumor-free until 64.6 weeks of age
|
|
• mice develop osteosarcoma within 10.3 weeks of age
• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels
• treatment of mice with RANK-Fc for 52 weeks beginning at 12.6 weeks of age keeps mice tumor-free until 64.6 weeks of age
|
|
• in a scratch wound healing assay, tumor cells show greater migration than tumor cells from conditional Rb1tm2Brn heterozygous Trp53tm1Brn homozygous double mutants
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:234128 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice do not live longer than 11 weeks
• treatment of mice with RANK-Fc prolongs survival to around to around 13.3 weeks
|
|
• mice develop osteosarcoma within 6.3 weeks of age
• tumors are marked by high (TNFSF11) RANKL/low (TNFRSF11A) RANK levels
• treatment of mice with RANK-Fc starting at 2.4 weeks of age suppresses tumor growth
• mice develop tumors 4.3 weeks after the discontinuation of RANK-Fc treatment and large numbers of osteoclasts are seen lining the boundary of tumor cells and adjacent osteopetrotic bone
|
|
• mice develop osteosarcoma within 6.3 weeks of age
• tumors are marked by high (TNFSF11) RANKL/low (TNFRSF11A) RANK levels
• treatment of mice with RANK-Fc starting at 2.4 weeks of age suppresses tumor growth
• mice develop tumors 4.3 weeks after the discontinuation of RANK-Fc treatment and large numbers of osteoclasts are seen lining the boundary of tumor cells and adjacent osteopetrotic bone
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:234128 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• death within 3 months of tamoxifen treatment
|
|
• small cell lung tumors 2.5 months after tamoxifen treatment
|
|
• increased proliferation of pulmonary neuroendocrine cells
|
|
• all mice develop thyroid tumors
|
|
• increased invasiveness at 2.5 months after tamoxifen treatment
|
|
• small cell lung tumors 2.5 months after tamoxifen treatment
|
|
• all mice develop thyroid tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle predominantly develop poorly differentiated, well-circumscribed neoplasms with similarity to supratentorial primitive neuroectodermal tumors (sPNET)
• expression profiles of tumors resemble human atypical teratoid/rhabdoid tumor
|
|
• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle predominantly develop poorly differentiated, well-circumscribed neoplasms with similarity to supratentorial primitive neuroectodermal tumors (sPNET)
• expression profiles of tumors resemble human atypical teratoid/rhabdoid tumor
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle predominantly develop poorly differentiated, well-circumscribed neoplasms with similarity to supratentorial primitive neuroectodermal tumors (sPNET)
• expression profiles of tumors resemble human atypical teratoid/rhabdoid tumor
|
|
• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle predominantly develop poorly differentiated, well-circumscribed neoplasms with similarity to supratentorial primitive neuroectodermal tumors (sPNET)
• expression profiles of tumors resemble human atypical teratoid/rhabdoid tumor
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• low penetrance (8.33%) of osteosarcomas with a long latency of 338 days of age on average
|
|
• low penetrance (8.33%) of osteosarcomas with a long latency of 338 days of age on average
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die from around 250 to 375 days of age
|
|
• tumors show metastasis, most frequently to the lung and then the liver
|
|
• complete penetrance of osteosarcomas with an average latency of 292 days
|
|
• complete penetrance of osteosarcomas with an average latency of 292 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a shortened overall survival, with a median lifespan of 184 days versus 239 days in control littermates that are wild-type for Dlg2
|
|
• tumor cells are more proliferative than those in control littermates that are wild-type for Dlg2, as indicated by Ki-67 staining
|
|
• mice show accelerated osteosarcoma development with anatomical distribution and histological features similar to those in control littermates that are wild-type for Dlg2
• osteoblastic tumors are aggressive in nature, as indicated by abundant osteoid deposition at the invasive front of thoracic vertebra osteosarcomas
• plump tumorous osteoblasts and massive osteoid deposition are seen in tumors that develop at different sites
|
|
• at 22 weeks of age, mice show accelerated tumor onset with visible signs of osteosarcomas on the tibia and ribs, unlike control littermates that are wild-type for Dlg2
|
|
• mice show accelerated osteosarcoma development with anatomical distribution and histological features similar to those in control littermates that are wild-type for Dlg2
• osteoblastic tumors are aggressive in nature, as indicated by abundant osteoid deposition at the invasive front of thoracic vertebra osteosarcomas
• plump tumorous osteoblasts and massive osteoid deposition are seen in tumors that develop at different sites
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• large cell carcinoma
|
|
• choroid plexus papilloma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice survive up to 55.4 weeks of age
|
|
• mice develop osteosarcoma by 35 weeks of age
• tumors are marked by low TNFSF11 (RANKL)/high TNFRSF11A (RANK) levels
|
|
• mice develop osteosarcoma by 35 weeks of age
• tumors are marked by low TNFSF11 (RANKL)/high TNFRSF11A (RANK) levels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice survive up to 38.1 weeks of age
|
|
• mice develop osteosarcoma by 20 weeks of age
|
|
• mice develop osteosarcoma by 20 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• death within 6-7 months of tamoxifen treatment
|
|
• small cell lung tumors 5-6 months after tamoxifen treatment in 4 of 32 mice examined, all with pulmonary neuroendocrine cells hyperplasia as well
|
|
• pulmonary neuroendocrine cells hyperplasia 5-6 months after tamoxifen treatment in 16 of 32 mice examined
• increased proliferation of pulmonary neuroendocrine cells
|
|
• all mice develop thyroid tumors
|
|
• small cell lung tumors 5-6 months after tamoxifen treatment in 4 of 32 mice examined, all with pulmonary neuroendocrine cells hyperplasia as well
|
|
• all mice develop thyroid tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumor-free survival is 146.5 days
|
|
• 52.4% incidence
|
|
• 52.4% incidence
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• impaired survival is seen beginning around 2 months of age
• death appears to result from excessive bleeding due to invasion of uterine blood vessels by tumor cells
|
|
|
• hyperplasia progresses to carcinoma by 3 weeks of age
|
|
|
• by P10, luminal and glandular epithelial hyperplasia are seen
|
|
|
• enlarged relative to conditional mutants that are wild type for Trp53
|
|
|
• hyperplasia progresses to carcinoma by 3 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| endometrial cancer | DOID:1380 |
OMIM:608089 |
J:139053 | |
|
|
| ♀ | 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 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 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 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 |
|
• 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 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 |
|
• tumor free survival time is increased compared to mutant mice wild-type for Sox2
|
|
• compared to mutant mice wild-type for Sox2
• tumors are uniformly Sox2 positive
|
|
• compared to mutant mice wild-type for Sox2
• tumors are uniformly Sox2 positive
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumor free survival time is increased compared to mutant mice wild-type for Sox2
|
|
• compared to mutant mice wild-type for Sox2
• tumors are uniformly Sox2 positive
|
|
• compared to mutant mice wild-type for Sox2
• tumors are uniformly Sox2 positive
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased tumor free survival time
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 2 weeks of tamoxifen treatment
|
|
• widespread high-grade dysplasia and numerous intramucosal carcinomas invading the lamina propria in most of the small-bowel crypts and villi within 2 weeks of tamoxifen treatment
|
|
• increased proliferation after tamoxifen treatment throughout the crypt-villus axis
|
|
• in the gut of tamoxifen treated mice but no more so than in Csnk1a1tm1.1Ybn/Csnk1a1tm1.1Ybn Tg(Vil-cre/ERT2)23Syr mice
|
|
• increased proliferation after tamoxifen treatment throughout the crypt-villus axis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• within 6 months, 7 of 9 tamoxifen-treated mice develop invasive carcinomas that permeates the bowel muscular wall into the subserosal fat with some involvement of the serosal surface (stage T4)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time is shorter than in mutant mice wild-type for Smad4
• median survival time of 17.05 weeks
|
 |
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
• tumors are more aggressive than in mutant mice wild-type for Smad4
|
|
• bone metastases are seen in some (3 of 24) mice unlike in mutant mice wild-type for Smad4
|
|
|
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
• tumors are more aggressive than in mutant mice wild-type for Smad4
|
|
|
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
• tumors are more aggressive than in mutant mice wild-type for Smad4
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.2 months of age and no distant metastases are seen
|
|
• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.2 months of age and no distant metastases are seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop mammary gland carcinoma with a median tumor-free survival of 10.4 months of age
• tumors are invasive ductal carcinomas with a squamous component, however lobular carcinomas are not seen
|
|
• 33% of mice show lung metastasis
|
|
• mice develop mammary gland carcinoma with a median tumor-free survival of 10.4 months of age
• tumors are invasive ductal carcinomas with a squamous component, however lobular carcinomas are not seen
|
|
• mice develop mammary gland carcinoma with a median tumor-free survival of 10.4 months of age
• tumors are invasive ductal carcinomas with a squamous component, however lobular carcinomas are not seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases
|
|
• mice develop gastric adenocarcinomas with a median tumor-free survival of 9.4 months but do not develop distant metastases
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most common cause of death is duodenal obstruction, followed by gastric outlet obstruction
|
|
• 36% of mice develop duodenal adenocarcinomas
|
|
• 84% of mice develop spontaneous tumors in the glandular stomach with a median tumor-free survival of 8 months
• gastric tumors resemble diffuse-type gastric adenocarcinomas, are E-cadherin-negative, and are invasive into the muscle layers and regional lymph nodes
• intramucosal adenocarcinomas with signet ring cell feature is seen in 2 of 4 mice at 6 months of age
• gastric premalignant lesions such as atrophic gastritis, metaplasia or dysplasia are not seen at 4 and 5 months of age
|
|
• 3 of 21 mice with gastric adenocarcinomas develop lung metastases
• metastatic lesions have similar cytologic features to primary gastric tumors
• 8% of mice exhibit adenocarcinomas in the pancreas, most likely due to invasion of the primary duodenal or gastric adenocarcinomas
|
|
• 24% of mice develop forestomach squamous cell carcinomas
|
|
• 36% of mice develop duodenal adenocarcinomas
|
|
• 84% of mice develop spontaneous tumors in the glandular stomach with a median tumor-free survival of 8 months
• gastric tumors resemble diffuse-type gastric adenocarcinomas, are E-cadherin-negative, and are invasive into the muscle layers and regional lymph nodes
• intramucosal adenocarcinomas with signet ring cell feature is seen in 2 of 4 mice at 6 months of age
• gastric premalignant lesions such as atrophic gastritis, metaplasia or dysplasia are not seen at 4 and 5 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| stomach cancer | DOID:10534 |
OMIM:613659 |
J:212549 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumor-free survival is 398 days compared to 146.5 days in mutant mice wild-type for Nell1
|
|
• 85.2% decrease in the proliferative-index in tumors compared to tumors in mutant mice wild-type for Nell1
|
|
• 66.1% decrease in tumor-associated vasculature compared to mutant mice wild-type for Nell1
|
|
• 15.8% incidence compared to 52.4% incidence in mutant mice wild-type for Nell1
|
|
• 15.8% incidence compared to 52.4% incidence in mutant mice wild-type for Nell1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after adenoviral cre treatment, double mutant OSE cells show significantly enhanced proliferation compared to control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• medullary thyroid carcinomas in 2 of 13 mice treated with a cre-expressing adenovirus
(J:86077)
• following treatment with cre-expressing adenovirus, 2 of 13 mice exhibit medullary thyroid carcinoma unlike wild-type mice
(J:157319)
|
|
• mice treated with cre-expressing adenovirus median tumor-free survival is 475 days
|
|
• in some mice treated with a cre-expressing adenovirus
(J:86077)
• in some mice following treatment with cre-expressing adenovirus
(J:157319)
|
|
• large in 5 of 13 mice treated with a cre-expressing adenovirus
(J:86077)
• in some mice following treatment with cre-expressing adenovirus
(J:157319)
|
|
• medullary thyroid carcinomas in 2 of 13 mice treated with a cre-expressing adenovirus
(J:86077)
• following treatment with cre-expressing adenovirus, 2 of 13 mice exhibit medullary thyroid carcinoma unlike wild-type mice
(J:157319)
|
|
• mice treated with cre-expressing adenovirus median tumor-free survival is 475 days
|
|
• in some mice treated with a cre-expressing adenovirus
(J:86077)
• in some mice following treatment with cre-expressing adenovirus
(J:157319)
|
|
• large in 5 of 13 mice treated with a cre-expressing adenovirus
(J:86077)
• in some mice following treatment with cre-expressing adenovirus
(J:157319)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• after a single ovarian intrabursal injection of an adenovirus expressing Cre, mutant females develop epithelial ovarian cancer similar in progression of disease in women, with ovarian neoplasms spreading, forming ascites and metastasizing to the contralateral ovary, the lung and the liver
• 39% are well-differentiated serous epithelial neoplasms of the ovary and 45% are poorly differentiated CK8-positive neoplasms of the ovary
|
|
|
• the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma
|
|
• medullary thyroid carcinomas in some mice treated with a cre-expressing adenovirus
(J:86077)
• following treatment with cre-expressing adenovirus, 6 of 33 mice develop medullary thyroid carcinoma unlike wild-type mice
(J:157319)
|
|
• 97% of mice succumb to ovarian tumors at a median age of 227 days after after a single ovarian intrabusal injection of an adenovirus expressing Cre
|
|
|
• after a single ovarian intrabursal injection of an adenovirus expressing Cre, mutant females develop epithelial ovarian cancer similar in progression of disease in women, with ovarian neoplasms spreading, forming ascites and metastasizing to the contralateral ovary, the lung and the liver
• 39% are well-differentiated serous epithelial neoplasms of the ovary and 45% are poorly differentiated CK8-positive neoplasms of the ovary
|
|
|
• the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma
|
|
• medullary thyroid carcinomas in some mice treated with a cre-expressing adenovirus
(J:86077)
• following treatment with cre-expressing adenovirus, 6 of 33 mice develop medullary thyroid carcinoma unlike wild-type mice
(J:157319)
|
|
• various metastases in some mice treated with a cre-expressing adenovirus
|
|
• 15% of tumors that form in females after a single ovarian intrabursal injection of an adenovirus expressing Cre metastasized to the opposite ovary, 18% of tumors metastasized to the lung, and 6% of tumors metastasized to the liver
|
|
• mice treated with cre-expressing adenovirus median tumor-free survival is 210 days
|
|
• bronchioalveolar carcinomas in some mice treated with a cre-expressing adenovirus
|
|
• mice treated with a cre-expressing adenovirus exhibit multiple dysplastic foci of clustering small cells in the bronchial and bronchiolar mucosa
(J:86077)
• mice treated with cre-expressing adenovirus exhibit dysplastic foci of clustering small cells in the bronchial and bronchiolar mucosa unlike in wild-type mice
(J:157319)
|
|
|
• after a single ovarian intrabursal injection of an adenovirus expressing Cre, mutant females develop epithelial ovarian cancer similar in progression of disease in women, with ovarian neoplasms spreading, forming ascites and metastasizing to the contralateral ovary, the lung and the liver
• 39% are well-differentiated serous epithelial neoplasms of the ovary and 45% are poorly differentiated CK8-positive neoplasms of the ovary
|
|
|
• the ovarian cancer found after a single ovarian intrabursal injection of an adenovirus expressing Cre is characterisitic of serous adenocarcinoma
|
|
• mice treated with cre-expressing adenovirus median tumor-free survival is 210 days
|
|
• bronchioalveolar carcinomas in some mice treated with a cre-expressing adenovirus
|
|
• mice treated with a cre-expressing adenovirus exhibit multiple dysplastic foci of clustering small cells in the bronchial and bronchiolar mucosa
(J:86077)
• mice treated with cre-expressing adenovirus exhibit dysplastic foci of clustering small cells in the bronchial and bronchiolar mucosa unlike in wild-type mice
(J:157319)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung small cell carcinoma | DOID:5409 |
OMIM:182280 |
J:86077 , J:157319 | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:84345 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 53% of mice induced with tamoxifen at P0 and P1 develop non-CNS tumors or other type of brain tumors
|
|
• 53% of mice induced with tamoxifen at P0 and P1 develop non-CNS tumors or other type of brain tumors
|
|
• 47% of mice induced with tamoxifen at P0 and P1 develop medulloblastoma with a median onset of morbidity of 135 days
|
|
• 53% of mice induced with tamoxifen at P0 and P1 develop non-CNS tumors or other type of brain tumors
|
|
• 47% of mice induced with tamoxifen at P0 and P1 develop medulloblastoma with a median onset of morbidity of 135 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 8 weeks after adenoCre treatment, lungs show rapid cancer progression with increased proliferation compared to Trp53-sufficient mice
• tumors show nodules composed of central papillary structures with solid peripheral areas
• all double mutants show increased proliferation, and cells show altered nuclear morphology, while Trp53 conditional single mutants have normal lung phenotypes
|
|
• 2/5 mice are found to have prominent adenocarcinomas, composed of glandular structures lined by atypical cells with enlarged nuclei, hyperchromasia, contour irregularities, and prominent nucleoli
• large areas of necrosis are present in adenocarcinomas, with evidence of lymphatic and vascular invasion
|
|
• 8 weeks after adenoCre treatment, lungs show rapid cancer progression with increased proliferation compared to Trp53-sufficient mice
• tumors show nodules composed of central papillary structures with solid peripheral areas
• all double mutants show increased proliferation, and cells show altered nuclear morphology, while Trp53 conditional single mutants have normal lung phenotypes
|
|
• 2/5 mice are found to have prominent adenocarcinomas, composed of glandular structures lined by atypical cells with enlarged nuclei, hyperchromasia, contour irregularities, and prominent nucleoli
• large areas of necrosis are present in adenocarcinomas, with evidence of lymphatic and vascular invasion
|
|
• 8 weeks after Cre treatment, some small airways display papillary hyperplasia, not seen in Braf-conditional mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice treated with a cre-expressing adenovirus exhibit metastasis in the mediastinum, ovary and adrenal gland
|
|
• in some mice treated with a cre-expressing adenovirus
|
|
• small in some mice treated with a cre-expressing adenovirus
|
|
• in some mice treated with a cre-expressing adenovirus
|
|
• small in some mice treated with a cre-expressing adenovirus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 100% of mice induced with tamoxifen at P0 and P1 develop medulloblastoma with a median onset of morbidity of 63 days of age
• medullablastomas of tamoxifen treated mice show extensive and abnormal vascularization and highly differentiated tumor cells surrounding a perivascular tumor stem cell niche that is not seen in single Trp53 conditional mutants
• blood clots are often seen in the lumen of abnormal blood vessels
• medulloblastoma initiates from a perivascular tumor stem cell niche
• medulloblastomas of tamoxifen treated mice acquire somatic inactivation of Ptch1 and show expression signatures of sonic hedgehog subgroup medulloblastoma
|
|
• 18 of 26 mice treated with tamoxifen at P0 and P1 develop gliomas in the forebrain and brain stem
|
|
• 100% of mice induced with tamoxifen at P0 and P1 develop medulloblastoma with a median onset of morbidity of 63 days of age
• medullablastomas of tamoxifen treated mice show extensive and abnormal vascularization and highly differentiated tumor cells surrounding a perivascular tumor stem cell niche that is not seen in single Trp53 conditional mutants
• blood clots are often seen in the lumen of abnormal blood vessels
• medulloblastoma initiates from a perivascular tumor stem cell niche
• medulloblastomas of tamoxifen treated mice acquire somatic inactivation of Ptch1 and show expression signatures of sonic hedgehog subgroup medulloblastoma
|
|
• 18 of 26 mice treated with tamoxifen at P0 and P1 develop gliomas in the forebrain and brain stem
|
|
• cerebellum at P21 of mice treated with tamoxifen at birth shows disrupted lamination and abundant Ki67+ proliferative cells throughout the cerebellum , which are concentrated around blood vessels either under the pial surface or in the parenchyma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| medulloblastoma | DOID:0050902 |
OMIM:155255 |
J:237990 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 92% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or poorly differentiated adenocarcinoma
|
|
• 92% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or poorly differentiated adenocarcinoma
|
|
• 92% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or poorly differentiated adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with cells from Trp53tm1Brn homozygotes transfected with a lacZ-expressing adenoviru
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• early B cell development is rescued in tamoxifen treated mice
|
|
• reduced LSK and lymphoid-primed multipotent progenitors in tamoxifen-treated mice
|
|
• tamoxifen-treated LSK cells exhibit a complete loss of lymphoid development
|
| N |
• early B cell development is rescued in tamoxifen treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4/4 of mice receiving 4 Gy radiation at P5 develop cerebellar tumors by 5 months of age
|
|
• 4/4 of mice receiving 4 Gy radiation at P5 develop cerebellar tumors by 5 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| medulloblastoma | DOID:0050902 |
OMIM:155255 |
J:102702 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike mice with conditional loss of Pten, endometrial morphology and histology appear normal through 5 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased proliferation in the entire bowel
• distal gut dysplasia appears later than in mice with Trp53tm2.1Tyj (containing the R172H missense mutation)
|
|
• jejunal and ileal organoids exhibit increased proliferation, decreased differentiation, and resemble highly dysplastic spheroids
|
|
• high-grade dysplasia in the entire bowel
|
|
• enlarged and dysplastic
|
|
• enlarged and dysplastic
|
|
• increased proliferation in the entire bowel
• distal gut dysplasia appears later than in mice with Trp53tm2.1Tyj (containing the R172H missense mutation)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice succumb to pancreatic ductal adenocarcinoma (PDAC) at a median age of 7.9 weeks following doxycycline treatment at 3 weeks of age
|
|
• all mice succumb to pancreatic ductal adenocarcinoma (PDAC) at a median age of 7.9 weeks following doxycycline treatment at 3 weeks of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:186194 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice succumb to pancreatic ductal adenocarcinoma (PDAC) between 11 and 25 weeks of age following doxycycline treatment at 3 weeks of age
• tumors exhibit features of human PDAC, including glandular tumor structures, exuberant stroma, local invasion into surrounding structures such as the duodenum, and distant metastases to the liver and lung
• mice show rapid tumor regression staring 48 hours and peaking at 72 hours following doxycycline withdrawal, with a reduction in tumor mass of about 50% after 1 week of doxycycline withdrawal; tumor regression is accompanied by decreased tumor cell proliferation and increased apoptosis
• withdrawal of doxycycline results in decreased glucose uptake and lactate production by cells in vitro
|
|
• all mice succumb to pancreatic ductal adenocarcinoma (PDAC) between 11 and 25 weeks of age following doxycycline treatment at 3 weeks of age
• tumors exhibit features of human PDAC, including glandular tumor structures, exuberant stroma, local invasion into surrounding structures such as the duodenum, and distant metastases to the liver and lung
• mice show rapid tumor regression staring 48 hours and peaking at 72 hours following doxycycline withdrawal, with a reduction in tumor mass of about 50% after 1 week of doxycycline withdrawal; tumor regression is accompanied by decreased tumor cell proliferation and increased apoptosis
• withdrawal of doxycycline results in decreased glucose uptake and lactate production by cells in vitro
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:186194 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 1 in 12 mice develop an rhabdomyosarcoma by day 202
|
|
• 1 in 12 mice develop an rhabdomyosarcoma by day 202
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| alveolar rhabdomyosarcoma | DOID:4051 |
OMIM:268220 |
J:93444 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• earlier tumor onset, from 32 to 65 days of age
• bortezomib treated mice have better survival
|
|
• earlier tumor onset, from 32 to 65 days of age
• bortezomib treated mice have better survival
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2 in 5 mice develop an rhabdomyosarcoma by day 75 to 91
|
|
• 2 in 5 mice develop an rhabdomyosarcoma by day 75 to 91
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| alveolar rhabdomyosarcoma | DOID:4051 |
OMIM:268220 |
J:93444 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Skin hyperpigmentation in Csnk1a1tm1.1Ybn/Csnk1a1tm1.1Ybn Tg(KRT14-cre/ERT)20Efu/0 mice but not in Csnk1a1tm1.1Ybn/Csnk1a1tm1.1Ybn Trp53tm1Brn/Trp53tm1Brn Tg(KRT14-cre/ERT)20Efu/0 mice
|
• after tamoxifen i.p. treatment, the epidermis becomes dysplastic with no melanin deposition
|
|
• at day 28 after tamoxifen i.p. treatment, BrdU+ (proliferating) cells and beta-catenin nuclear staining are increased in the basal layer of the epidermis; however, most of the positive cells are multinucleated clumping cells indicating abnormal mitoses associated with epidermal dysplasia
|
| N |
• mice do NOT develop skin hyperpigmentation after tamoxifen i.p. treatment
• melanin is mainly distributed in the dermis and less in the epidermis, similar to control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice survive to around 17 weeks of age
|
|
• mice develop osteosarcoma within 17 weeks of age
• multiple tumors among long bones, spine, jaw, and skull
• tumors are composed of malignant-appearing osteoblasts with woven bone as the predominant matrix and occasional chondroblastic or fibroblastic phenotype
• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels
|
|
• mice develop osteosarcoma within 17 weeks of age
• multiple tumors among long bones, spine, jaw, and skull
• tumors are composed of malignant-appearing osteoblasts with woven bone as the predominant matrix and occasional chondroblastic or fibroblastic phenotype
• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:234128 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• excessive scratching behavior resulting in dermatitis around the neck, earlobes, and the flank region
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• excessive scratching behavior resulting in dermatitis around the neck, earlobes, and the flank region
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lesions in the white matter of the corpus callosum and cingulum
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severe scratching behavior
|
|
• mice exhibit intermittent episodes of tail extension and dystonic posturing of the body, frequently in response to handling
|
|
• motor coordination problems become evident from around 3 weeks of age
|
|
• abnormal posture of the hind limbs
|
|
• mice exhibit tumbling repeatedly during attempted locomotion; mice frequently fall over and repeatedly lift and replace the same paw in various positions during each stride
|
|
• mice exhibit a non-uniform gait, with uneven stride length and width, dragging of the hindpaws and an inability to keep the hindquarters upr
|
|
• uneven stride length
|
|
• many mice appear lethargic with hind limb paralysis
|
|
• mice exhibit clear seizures or intermittent electrographic seizures associated either with forelimb clonus, evolving into body jerking, and wild running or arrest of activity during the ictal EEG discharges
|
|
• altered granule neuron migration, with some granule neurons failing to migrate out of the external germinal layer, others remaining trapped in the molecular layer
• altered cerebellar granule neuron migration is already seen at 3 weeks of age
|
|
• body weight is reduced by about 40%
|
|
• mice require water gel for survival
|
|
• mice exhibit intermittent episodes of tail extension and dystonic posturing of the body, frequently in response to handling
|
|
• mice develop brain tumors starting at around 1 month of age
• mice that die suddenly exhibit presence of high-grade, aggressive tumors that infiltrate and obliterate the surrounding cerebellar folia
• tumors appear to arise from the cerebellum
• tumors show hallmarks of atypical teratoid/rhabdoid tumor of the central nervous system
|
|
• mice exhibit clear seizures or intermittent electrographic seizures associated either with forelimb clonus, evolving into body jerking, and wild running or arrest of activity during the ictal EEG discharges
|
|
• altered granule neuron migration, with some granule neurons failing to migrate out of the external germinal layer, others remaining trapped in the molecular layer
• altered cerebellar granule neuron migration is already seen at 3 weeks of age
|
|
• mice develop brain tumors starting at around 1 month of age
• mice that die suddenly exhibit presence of high-grade, aggressive tumors that infiltrate and obliterate the surrounding cerebellar folia
• tumors appear to arise from the cerebellum
• tumors show hallmarks of atypical teratoid/rhabdoid tumor of the central nervous system
|
|
• defects in white matter with complete loss of tissue in regions of white matter over time
• white matter fiber tracks are reduced
• loss of white matter is already seen at 3 weeks of age
|
|
• defects in the corpus callosum
• lesions in the corpus callosum are already seen at 3 weeks of age
|
|
• defects in the hippocampus
|
|
• reduced cerebral cortex is already seen at 3 weeks of age
|
|
• defects in the cytoarchitecture of the cerebellum
• progressive loss of cells and neuronal projections in the cerebellum
|
|
• aberrant external germinal layer
|
|
• the boundary between the internal granule layer and the molecular layer remains diffuse
|
|
• loss of oligodendrocytes with age
|
|
• high level of gliosis in the fiber tracks and in the molecular layer and in the remnants of the external germinal layer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| central nervous system cancer | DOID:3620 | J:226786 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3 of 16 mice injected with endoxifen develop glial tumors with lesions of different sizes and varying extents of infiltration
• small neoplastic lesions in endoxifen-induced mice arise from beneath the SVZ and extend into the striatum and dorsally into the corpus callosum
• larger tumors of endoxifen-induced mice show expansion into and a diffuse infiltration of the entire caudate nucleus
• some tumors contain areas of necrosis and occasional microvascular proliferations similar to those in malignant gliomas
|
|
• endoxifen-induced tumors show glial morphology with features typical of astrocytomas and oligodendrogliomas
|
|
• endoxifen-induced tumors show glial morphology with features typical of astrocytomas and oligodendrogliomas
|
|
• 3 of 16 mice injected with endoxifen develop glial tumors with lesions of different sizes and varying extents of infiltration
• small neoplastic lesions in endoxifen-induced mice arise from beneath the SVZ and extend into the striatum and dorsally into the corpus callosum
• larger tumors of endoxifen-induced mice show expansion into and a diffuse infiltration of the entire caudate nucleus
• some tumors contain areas of necrosis and occasional microvascular proliferations similar to those in malignant gliomas
|
|
• endoxifen-induced tumors show glial morphology with features typical of astrocytomas and oligodendrogliomas
|
|
• endoxifen-induced tumors show glial morphology with features typical of astrocytomas and oligodendrogliomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| high grade glioma | DOID:3070 |
OMIM:PS137800 |
J:229481 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 2/5 (40%) of mice receiving 4 Gy radiation at P5 develop cerebellar tumors by 5 months of age
|
|
• 2/5 (40%) of mice receiving 4 Gy radiation at P5 develop cerebellar tumors by 5 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants; tumor size varies with age and genotype
• an early-stage tumor displayed a pronounced vitreal protrusion in one animal, and contained structures resembling neuronal processes like those in the plexiform layer of the normal retina
• in tumors, proteins usually found in amacrine/horizontal cells, including Gad65, Snap25, Calbindin, vGlut-1, E-cadherin, N-cadherin, synapsin, and Syntaxin-1 are expressed; these cells are considered to be differentiated
• cells positive for amacrine/horizontal cell markers (1.7-3.6 x 106 cells/tumor) are much more numerous than number of amacrine/horizontal cells in a normal retina
• regions of tumors negative for amacrine/horizontal markers contain more densely packed nuclei
|
|
• tumor cells that invade the anterior eye chamber beneath the cornea are densely packed stage II cells surrounded by sparse regions of plexus with no synaptic densities or vesiclesin in the plexus or rosettes of these cells
• tumor cells have abundant mitochondria and mitotic figures; some rosettes have a central plexus made up of large, undifferentiated processes, with other rosettes having a central plexus containing neurons and synapses
|
|
• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in smaller areas of plexus in tumors
• processes are usually smaller in diameter (<0.5 um) but large ones of 1-3 um are observed occasionally; variety of synaptic arrangements occur and all types can be found in contacts among processes, while ribbon synapses are seen only in areas near photoreceptor cell bodies
|
|
• significant disruptions in retinal morphology are observed by P12 to 13
• in diseased eyes, retina blastoma cells rupture the inner limiting membrane (ILM), particularly by the apex of vitreal protrusions that may be present; at these points, tumor cell bodies and associated vasculature can be seen
|
|
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants; tumor size varies with age and genotype
• an early-stage tumor displayed a pronounced vitreal protrusion in one animal, and contained structures resembling neuronal processes like those in the plexiform layer of the normal retina
• in tumors, proteins usually found in amacrine/horizontal cells, including Gad65, Snap25, Calbindin, vGlut-1, E-cadherin, N-cadherin, synapsin, and Syntaxin-1 are expressed; these cells are considered to be differentiated
• cells positive for amacrine/horizontal cell markers (1.7-3.6 x 106 cells/tumor) are much more numerous than number of amacrine/horizontal cells in a normal retina
• regions of tumors negative for amacrine/horizontal markers contain more densely packed nuclei
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
|
|
• tumor cells that invade the anterior eye chamber beneath the cornea are densely packed stage II cells surrounded by sparse regions of plexus with no synaptic densities or vesiclesin in the plexus or rosettes of these cells
• tumor cells have abundant mitochondria and mitotic figures; some rosettes have a central plexus made up of large, undifferentiated processes, with other rosettes having a central plexus containing neurons and synapses
|
|
• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in extensive plexus areas of tumors
|
|
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
|
|
• a substantial proportion of tumor cells expressing amacrine/horizontal cell markers are proliferating as shown by labeled thymidine incorporation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significant disruptions in retinal morphology are observed by P12 to 13
|
|
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants, but onset is delayed compared to that observed in Rbl1 homozygous compound mutants
• tumor size varies with age and genotype
• mice show rapid filling of the vitreal cavity with densely packed tumor cells and rosettes; in the tumors, there is an overabundance of stage II retinoblastoma cells
• near outer surface of retina near tumor origin site, there are regions of plexus with synaptic densities and synaptic vesicles, indistinguishable from the Rb1;Rbl1 mutants that are wild-type for Trp53
|
|
• significant disruptions in retinal morphology are observed by P12 to 13
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with adenovirus expressing Cre (AdCre) into the bladder at 2-3 months of age start to die at 6 months of age and have a median survival of 10.2 months
• mice injected with AdCre intraperitoneally exhibit a median survival of 8.5 months and 89% of mice die during one year of follow-up after AdCre injection
|
|
• 73% of mice injected with AdCre into the bladder exhibit mesothelioma
• 85% of mice injected with AdCre intraperitoneally develop mesothelioma
• malignant tumor, similar to epithelioid mesothelioma, is seen on all peritoneal surfaces, including the bladder, kidney, spleen, liver and intestines, without evidence of a primary site, in mice injected with AdCre
• mice that develop mesothelioma following AdCre injection and are treated with rapamycin for 5 weeks show inhibition of tumor growth
|
|
• mice injected with AdCre into the bladder often exhibit hemorrhagic ascites
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant mesothelioma | DOID:1790 |
OMIM:156240 |
J:212578 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with similarly treated cells from Trp53tm1Brn/Trp53tm3Tyj mice
|
|
|
| ♀ | 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:103407 , J:154041 , J:195492 , J:203686 | |
|
|
| ♀ | 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 |
|
• 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 |
| N |
• ovarian surface epithelium cells transfected with a cre-expressing adenovirus exhibit reduced invasion compared with similarly treated cells from Trp53tm1Brn/Trp53tm2Tyj mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• adeno-cre-treated mice die by 28 week
|
|
• by 6 months, adeno-cre-treated mice exhibit lung tumors unlike wild-type mice
• adeno-cre-treated mice exhibit few lung adenocarcinomas, adenocarcinomas with neuroendocrine features, large-cell neuroendocrine carcinoma, and large-cell carcinomas while most tumors resemble neuroendocrine small-cell lung tumors
|
|
• most tumors in adeno-cre-treated mice resemble those found in human neuroendocrine small cell lung cancer patients
|
|
• by 6 months, adeno-cre-treated mice exhibit lung tumors unlike wild-type mice
• adeno-cre-treated mice exhibit few lung adenocarcinomas, adenocarcinomas with neuroendocrine features, large-cell neuroendocrine carcinoma, and large-cell carcinomas while most tumors resemble neuroendocrine small-cell lung tumors
|
|
• most tumors in adeno-cre-treated mice resemble those found in human neuroendocrine small cell lung cancer patients
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung small cell carcinoma | DOID:5409 |
OMIM:182280 |
J:160148 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• adeno-cre-treated mice begin to die at 17 weeks and by 6 months all mice are moribund
|
|
• 3 and 6 months, adeno-cre-treated mice exhibit primary lung tumors with metastasis to the liver unlike wild-type mice
• at 3 and 6 month, adeno-cre-treated mice exhibit more tumors than in similarly treated Rb1tm3Tyj Trp53tm1Brn homozygotes
• adeno-cre-treated mice exhibit few lung adenocarcinomas, adenocarcinomas with neuroendocrine features, large-cell neuroendocrine carcinoma, and large-cell carcinomas while most tumors resemble neuroendocrine small-cell lung tumors
|
|
• most tumors in adeno-cre-treated mice resemble those found in human neuroendocrine small cell lung cancer patients
|
|
• 3 and 6 months, adeno-cre-treated mice exhibit primary lung tumors with metastasis to the liver unlike wild-type mice
• at 3 and 6 month, adeno-cre-treated mice exhibit more tumors than in similarly treated Rb1tm3Tyj Trp53tm1Brn homozygotes
• adeno-cre-treated mice exhibit few lung adenocarcinomas, adenocarcinomas with neuroendocrine features, large-cell neuroendocrine carcinoma, and large-cell carcinomas while most tumors resemble neuroendocrine small-cell lung tumors
|
|
• most tumors in adeno-cre-treated mice resemble those found in human neuroendocrine small cell lung cancer patients
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung small cell carcinoma | DOID:5409 |
OMIM:182280 |
J:160148 | |
|
|
| ♀ | 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 |
| 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 |
|
• 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 |
|
|
| ♀ | 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 |
|
|
| ♀ | 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 |
|
• mice develop lung tumors with a longer latency than seen in Col1a1tm4(CAG-FGFR2_iIIIb*K660N)Kkw mice after intranasal delivery of an adenovirus expressing cre recombinase, with a penetrance of 35%
|
|
• mice develop lung tumors with a longer latency than seen in Col1a1tm4(CAG-FGFR2_iIIIb*K660N)Kkw mice after intranasal delivery of an adenovirus expressing cre recombinase, with a penetrance of 35%
|
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:214230 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 92% of mice develop lung tumors with a latency of 28-32 weeks after intranasal delivery of an adenovirus expressing cre recombinase (Ad-cre)
• mice with lung tumors treated with a pan-FGFR inhibitor, BGJ-398, mice show more than 50% tumor regression
|
|
• tumors from Ad-cre treated mice resemble poorly differentiated human grade 3/4 lung adenocarcinoma displaying high pleiotropy and heavily multinucleated tumor cells showing local invasion throughout the lung parenchyma
|
|
• Ad-cre treated mice that become sick present with weight loss
|
|
• mice show a decrease in overall survival after Ad-cre treatment, beginning to die around 20 weeks after Ad-cre delivery and most dying by 50 weeks after Ad-cre administration
|
|
• 92% of mice develop lung tumors with a latency of 28-32 weeks after intranasal delivery of an adenovirus expressing cre recombinase (Ad-cre)
• mice with lung tumors treated with a pan-FGFR inhibitor, BGJ-398, mice show more than 50% tumor regression
|
|
• tumors from Ad-cre treated mice resemble poorly differentiated human grade 3/4 lung adenocarcinoma displaying high pleiotropy and heavily multinucleated tumor cells showing local invasion throughout the lung parenchyma
|
|
• Ad-cre treated mice that become sick present with progressive dyspnea and weight loss
|
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:214230 | |
|
|
| ♀ | 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 |
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation
|
|
• gamma-irradiated, tamoxifen-treated adult mice show accelerated thymic lymphoma formation
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice die between 100 and 200 days after irradiation
|
|
• gamma-irradiated, tamoxifen-treated adult mice show accelerated thymic lymphoma formation
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice die between 100 and 200 days after irradiation
|
|
|
| ♀ | 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 |
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation
|
|
• gamma-irradiated tamoxifen-treated mice die mainly of non-disseminated thymic lymphomas, unlike mice that are homozygous for Setd4tm1c(KOMP)Wtsiand heterozygous for Gt(ROSA)26Sortm1(cre/ERT2)Tyj where tumors are widely disseminated to other organs
|
|
• in gamma-irradiated tamoxifen-treated mice, thymic lymphomas are significantly larger in size/weight relative to those in mice that are only homozygous for Setd4tm1c(KOMP)Wtsiand heterozygous for Gt(ROSA)26Sortm1(cre/ERT2)Tyj
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice fail to display a delay in the development of radiation-induced thymic lymphomas
|
|
• sham-irradiated, tamoxifen-treated double mutant mice show accelerated spontaneous tumor development relative to mice that are only homozygous for Trp53tm1Brn and heterozygous for Gt(ROSA)26Sortm1(cre/ERT2)Tyj
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, most tamoxifen-treated adult mice die within 100 days post irradiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• sham-irradiated, tamoxifen-treated mice show no significant differences in spontaneous tumor development or survival relative to mice that are heterozygous for Trp53tm1Brn and Gt(ROSA)26Sortm1(cre/ERT2)Tyj but wild-type for Setd4
|
|
• after exposure to 4 weekly 2 Gy of total body gamma-irradiation, tamoxifen-treated adult mice fail to display a delay in the development of radiation-induced thymic lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival of about 6 months following tumor induction with tamoxifen
• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival
• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901show prolonged survival
|
|
• tamoxifen treated mice exhibit accelerated progression from papillary thyroid carcinoma to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis
• carcinoma in tamoxifen treated mice shows tracheal invasion and extrathyroidal extension
• marker analysis indicates that anaplastic thyroid carcinoma in tamoxifen treated mice originates from thyroid epithelium
• tumors from tamoxifen treated mice exhibit very slow initial growth upon induction but rapid tumor growth after a variable latency
• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels and develop anaplastic thyroid carcinoma with a similar latency as unsupplemented controls
• anaplastic thyroid carcinomas exhibit a gene expression profile of high-grade, undifferentiated carcinomas
• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival and a decrease in contralateral papillary thyroid carcinomas, however no decrease in anaplastic thyroid carcinoma size is seen and tumors even grow larger
• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901 show complete regression of tumors and prolonged survival
|
|
• 19% of tamoxifen treated mice exhibit lung metastases
• however, region lymph node metastases are not seen
|
|
• tamoxifen treated mice exhibit accelerated progression from papillary thyroid carcinoma to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis
• carcinoma in tamoxifen treated mice shows tracheal invasion and extrathyroidal extension
• marker analysis indicates that anaplastic thyroid carcinoma in tamoxifen treated mice originates from thyroid epithelium
• tumors from tamoxifen treated mice exhibit very slow initial growth upon induction but rapid tumor growth after a variable latency
• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels and develop anaplastic thyroid carcinoma with a similar latency as unsupplemented controls
• anaplastic thyroid carcinomas exhibit a gene expression profile of high-grade, undifferentiated carcinomas
• tumor induced mice treated with the BRAF inhibitor PLX4720 show improved survival and a decrease in contralateral papillary thyroid carcinomas, however no decrease in anaplastic thyroid carcinoma size is seen and tumors even grow larger
• tumor induced mice treated with both the BRAF inhibitor PLX4720 and the selective MEK inhibitor PD0325901 show complete regression of tumors and prolonged survival
|
|
• small increase in TSH levels (less than 10-fold elevation) in tamoxifen treated mice
• mice supplemented with L-thyroxine immediately following tamoxifen administration show suppressed TSH levels
|
|
• tamoxifen treated mice quickly deteriorate after progression to anaplastic thyroid carcinoma, with rapidly growing neck masses and development of audible respiratory stridor
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen treated mice exhibit accelerated progression to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis
|
|
• tamoxifen treated mice exhibit accelerated progression to poorly differentiated thyroid carcinoma and overt undifferentiated anaplastic thyroid carcinoma with highly pleomorphic, atypical cells with evidence of necrosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median tumor-free survival is significantly increased relative to mutant mice that are either homozygotes for the wild-type Prmt1 allele or heterozygotes with one wild-type and one floxed Prmt1 allele
|
|
• microPET/CT imaging suggested a reduction in the presence of osteosarcomas at 100 days of age
• osteosarcoma tumors retain residual PRMT1 protein expression and a nonexcised Prmt1 allele
|
|
• osteosarcoma initiation is delayed relative to mutant mice that are either homozygotes for the wild-type Prmt1 allele or heterozygotes with one wild-type and one floxed Prmt1 allele
|
|
• microPET/CT imaging suggested a reduction in the presence of osteosarcomas at 100 days of age
• osteosarcoma tumors retain residual PRMT1 protein expression and a nonexcised Prmt1 allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants have a median survival of 127 days of age
|
|
• 20.6% of mice show metastatic dissemination, commonly to the lung and liver
|
|
• seen in one mutant
|
|
• mutants develop osteosarcoma with a mean latency of 127 days
• 64.7% of tumors are found in the mandible/head, 11.8% of tumors are found on the lower long bones, and 23.5% of tumors are in other axial locations
• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma
|
|
• mutants develop osteosarcoma with a mean latency of 127 days
• 64.7% of tumors are found in the mandible/head, 11.8% of tumors are found on the lower long bones, and 23.5% of tumors are in other axial locations
• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:199542 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice begin to die at ~100 days of age and all die by around 200 days of age, with a median survival similar to that of mutant mice homozygous for the wild-type Prmt1 allele
|
|
• microPET/CT imaging suggested an increase in the presence of osteosarcomas at 100 days of age
|
|
• microPET/CT imaging suggested an increase in the presence of osteosarcomas at 100 days of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival is 19 weeks of age
|
|
• 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
|
|
• 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
|
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 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
|
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 |
|
|
• 70% of mice injected with a cre-expressing adenovirus (Ad-cre) under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• ovarian surface epithelium carcinomas that develop in mice intrabursally injected with Ad-cre show a range of morphologic patterns including papillary, micropapillary/filigree, microcystic, poorly differentiated adenocarcinoma, and solid/undifferentiated
• mice develop multifocal peritoneal carcinomatosis with tumor spread to all abdominal organs
|
|
|
• distant metastases are seen in the pleura of 87.5%, in the lung of 83% and in the liver of 46% of mutants intrabursally injected with Ad-cre that develop stage IV disease
|
|
|
• 2% of mice intrabursally injected with Ad-cre exhibit transformation of the oviduct epithelium, with lesions ranging from atypical hyperplasia, to carcinoma in situ to adenocarcinoma
|
|
|
• 70% of mice injected with a cre-expressing adenovirus (Ad-cre) under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• ovarian surface epithelium carcinomas that develop in mice intrabursally injected with Ad-cre show a range of morphologic patterns including papillary, micropapillary/filigree, microcystic, poorly differentiated adenocarcinoma, and solid/undifferentiated
• mice develop multifocal peritoneal carcinomatosis with tumor spread to all abdominal organs
|
|
|
• 2% of mice intrabursally injected with Ad-cre exhibit transformation of the oviduct epithelium, with lesions ranging from atypical hyperplasia, to carcinoma in situ to adenocarcinoma
• oviduct lesions are characterized by a glandular/acinar histology
|
|
|
• ovaries in intrabursally Ad-cre injected mice show hemorrhagic or serous ascites
|
|
|
• 70% of mice injected with a cre-expressing adenovirus (Ad-cre) under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• ovarian surface epithelium carcinomas that develop in mice intrabursally injected with Ad-cre show a range of morphologic patterns including papillary, micropapillary/filigree, microcystic, poorly differentiated adenocarcinoma, and solid/undifferentiated
• mice develop multifocal peritoneal carcinomatosis with tumor spread to all abdominal organs
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:189304 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 68% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• 68% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• 68% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:189304 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 72% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• 72% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• 72% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:189304 | |
|
|
| ♀ | 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 |
|
• all mice treated with an adenovirus expressing cre die by 6 months of age
|
|
• urinary bladder tumors in Adeno-cre treated mice are of epithelial origins and exhibit features of carcinoma in situ and high-grade invasive carcinoma with areas of transitional cell, squamous, and sarcomatoid carcinoma
|
|
• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice
• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm
• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation
|
|
• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice
• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm
• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:146760 | |
|
|
| ♀ | 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 |
|
• 1 in 19 (5%) mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology at a median latency of 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 |
|
• 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 |
|
• 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 |
|
• about 70% survival at 400 days of age, with some mice starting to die around 150 days of age
|
|
• tumors show metastasis, most frequently to the lung and then the liver
|
|
• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes
|
|
• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die from around 125 to 260 days of age
|
|
• tumors show metastasis, most frequently to the lung and then the liver
|
|
• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age
|
|
• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:136693 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age
(J:136693)
• lesions are seen as early as 2 months of age
(J:136693)
• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra
(J:136693)
• tumors exhibit a histology consistent with human medullary osteosarcoma
(J:136693)
• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues
(J:136693)
• metastasis is not seen but this may be due to rapid tumor development
(J:136693)
• mice maintained on doxycycline from conception until 4 weeks of age (preventing gene inactivation until removal of doxycycline), show delayed osteosarcoma development by about 100 days and these mice present with metastatic osteosarcoma but no head tumors
(J:136693)
• mice develop osteosarcomas with 100% penetrance at an average of 154.65 +/- 29.08 days of age
(J:318035)
• anatomic distribution of tumors includes the head and jaw (42.9%), limbs (38.8%), trunk (10.2%) and spine and sacrum (8.2%)
(J:318035)
|
|
• mice begin to die around 95 days of age and all die by 161 days of age
(J:136693)
• mice develop invasive, metastatic osteosarcomas and die within 20-35 weeks of age
(J:318035)
|
|
• slight growth delay that resolves with age
|
|
• mice develop metastatic tumor nodules in the lung
|
|
• about 20% of mice develop adipogenic tumors which occur on the outer chest or abdomen
|
|
• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age
(J:136693)
• lesions are seen as early as 2 months of age
(J:136693)
• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra
(J:136693)
• tumors exhibit a histology consistent with human medullary osteosarcoma
(J:136693)
• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues
(J:136693)
• metastasis is not seen but this may be due to rapid tumor development
(J:136693)
• mice maintained on doxycycline from conception until 4 weeks of age (preventing gene inactivation until removal of doxycycline), show delayed osteosarcoma development by about 100 days and these mice present with metastatic osteosarcoma but no head tumors
(J:136693)
• mice develop osteosarcomas with 100% penetrance at an average of 154.65 +/- 29.08 days of age
(J:318035)
• anatomic distribution of tumors includes the head and jaw (42.9%), limbs (38.8%), trunk (10.2%) and spine and sacrum (8.2%)
(J:318035)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:136693 , J:318035 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• overall survival is significantly longer than that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, regardless of whether tumors are located in the jaw or limbs
|
|
• osteosarcoma tumors exhibit a marked increase in mutant p27T187A levels while tumor lysates show elevated CDKN1B (p27) protein levels with similar SKP2 expression relative to tumors from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele
• treatment of early passage tumor cells with CHX (a protein synthesis inhibitor) and MG132 (a proteasome inhibitor) showed enhanced stability of the mutant p27T187A protein, with no significant change in Cdkn1b (p27) mRNA levels
• TUNEL and cleaved caspase-3 immunostaining showed increased apoptosis, while flow cytometry using annexin V/7-AAD staining showed a significant increase in the early
apoptotic population
• primary osteosarcoma tumor cells exhibit less sphere-forming capacity and show reduced stem-like properties (such as ALDH activity) and lower stem-cell frequency and self-renewal ability than tumor cells from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele
|
|
• both limb and jaw osteosarcoma tumors are significantly smaller than those from age-matched mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, indicating delayed tumor progression
• in vivo, tumor growth rate is significantly slower than that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele
• in vitro, primary osteosarcoma cells grown in monolayer cultures proliferate significantly less than tumor cells from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele
|
|
• mice develop osteosarcomas with 100% penetrance at an average of 169 +/- 43.69 days of age
• anatomic distribution of tumors is very similar to that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, including the head and jaw (40.7% versus 42.9%), limbs (39% versus 38.8%), spine and sacrum (10.2% versus 8.2%), and trunk (10.2% versus 10.2%)
|
|
• mice develop osteosarcomas with 100% penetrance at an average of 169 +/- 43.69 days of age
• anatomic distribution of tumors is very similar to that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, including the head and jaw (40.7% versus 42.9%), limbs (39% versus 38.8%), spine and sacrum (10.2% versus 8.2%), and trunk (10.2% versus 10.2%)
|
| N |
• mice show no evidence of delayed or stunted growth
|
| N |
• mice are fertile
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice start to die from around 125 days of age, although about 20% survive to 400 days of age
|
|
• tumors show metastasis, most frequently to the lung and then the liver
|
|
• 77.8% penetrance of osteosarcomas with an average latency of 177 days of age
|
|
• 77.8% penetrance of osteosarcomas with an average latency of 177 days of age
|
|
|
| ♀ | 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 |
|
|
• tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx
|
|
|
• increase in the rate of osteosarcoma initiation compared to mutant mice wild-type for Atrx
|
|
|
• tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx
|
|
|
| ♀ | 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 |
|
|
• tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx
|
|
|
• increase in the rate of osteosarcoma initiation compared to mutant mice wild-type for Atrx
|
|
|
• tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• show completely penetrant osteosarcoma formation between 4 and 8 months of age
|
|
• show completely penetrant osteosarcoma formation between 4 and 8 months of age
|
|
|
| ♀ | 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 |
|
• mice injected with an adenovirus expressing cre recombinase (Ad-Cre) into the left ventricle exhibit a 33.3% incidence of glioma
|
|
• in left ventricle Ad-cre injected mice
|
|
• in left ventricle Ad-cre injected mice
|
|
• mice injected with an adenovirus expressing cre recombinase (Ad-Cre) into the left ventricle exhibit a 33.3% incidence of glioma
|
|
• in left ventricle Ad-cre injected mice
|
|
• in left ventricle Ad-cre injected mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| high grade glioma | DOID:3070 |
OMIM:PS137800 |
J:229481 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the oral mucosa
|
|
• expanded spectrum of tissues affected by tumors compared to in Trp53tm1Brn/Trp53tm1Brn Tg(KRT14-cre)1Amc mice
|
|
• mice develop mammary tumor faster than Trp53tm1Brn/Trp53tm1Brn Tg(KRT14-cre)1Amc mice
|
|
• in the oral mucosa
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop mammary tumor faster than Trp53tm1Brn/Trp53+ Tg(KRT14-cre)1Amc mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle develop a spectrum of gliomas, including anaplastic astrocytomas, oligodendrogliomas, and most commonly, anaplastic oligoastrocytomas
• however, adeno-cre injected mice do not develop glioblastoma with palisading necrosis or microvascular proliferation
• tumors in adeno-cre injected mice resemble The Cancer Genome Atlas (TCGA) classical glioblastomas, Phillips proneural and TACG neural gliomas
|
|
• mice injected with an adeno-cre into the lateral ventricle develop anaplastic oligoastrocytoma
• oligoastrocytomas do not resemble any human gliobastoma subtypes
|
|
• mice injected with an adeno-cre into the lateral ventricle develop oligodendrogliomas
|
|
• mice injected with an adenovirus expressing cre (adeno-cre) into the lateral ventricle develop a spectrum of gliomas, including anaplastic astrocytomas, oligodendrogliomas, and most commonly, anaplastic oligoastrocytomas
• however, adeno-cre injected mice do not develop glioblastoma with palisading necrosis or microvascular proliferation
• tumors in adeno-cre injected mice resemble The Cancer Genome Atlas (TCGA) classical glioblastomas, Phillips proneural and TACG neural gliomas
|
|
• mice injected with an adeno-cre into the lateral ventricle develop anaplastic oligoastrocytoma
• oligoastrocytomas do not resemble any human gliobastoma subtypes
|
|
• mice injected with an adeno-cre into the lateral ventricle develop oligodendrogliomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• neuron loss is rescued by conditional knock-out of Trp53
|
|
• partially rescued by conditional knock-out of Trp53
|
|
• partial rescue of apoptosis and DNA damage by conditional knock-out of Trp53
|
|
• partially rescued by conditional knock-out of Trp53
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival is reduced compared to mutant mice wild-type for Trp53
|
|
• 80% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or adenosquamous carcinoma
• radial scar and poorly differentiated adenocarcinomas are also observed, although at a lower frequency than in mutant mice not carrying Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan
|
|
• at a lower rate than in mutant mice homozygous for Trp53tm1Brn
|
|
• 80% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or adenosquamous carcinoma
• radial scar and poorly differentiated adenocarcinomas are also observed, although at a lower frequency than in mutant mice not carrying Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan
|
|
• 80% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or adenosquamous carcinoma
• radial scar and poorly differentiated adenocarcinomas are also observed, although at a lower frequency than in mutant mice not carrying Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:170898 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most die early with lymphoma/thymoma
|
|
• some mice have small mammary tumors
|
|
• some mice have small mammary tumors
|
|
• some mice have small mammary tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop poorly differentiated thyroid cancer
|
|
• mice develop poorly differentiated thyroid cancer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| thyroid cancer | DOID:1781 | J:231492 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased incidence compared to mutant mice wild-type for Myc
|
|
• survival time is increased compared to mutant mice wild-type for Myc
|
|
• decreased incidence compared to mutant mice wild-type for Myc
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• at generations 3 and 4 (G3/4), all mice develop smaller, poorly progressive tumors compared to G0 mice
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
• most tumors fail to progress beyond HPIN by 24 weeks of age unlike in G0 mice
|
|
• smaller, poorly progressive tumors compared to tumors in G0 mice
• markedly increased apoptosis and decreased proliferation in tumor cells compared tumor cells from G0 mice
|
|
|
• at generations 3 and 4 (G3/4), all mice develop smaller, poorly progressive tumors compared to G0 mice
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
• most tumors fail to progress beyond HPIN by 24 weeks of age unlike in G0 mice
|
|
• reduced at G3/4
|
|
|
• at generations 3 and 4 (G3/4), all mice develop smaller, poorly progressive tumors compared to G0 mice
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
• most tumors fail to progress beyond HPIN by 24 weeks of age unlike in G0 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
|
|
|
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
|
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
|
|
|
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
|
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
|
|
|
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival time of 26.3 weeks
|
|
|
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
|
|
|
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
|
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
|
|
|
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
|
• all develop rapidly progressive, locally invasive prostate adenocarcinomas
|
|
|
• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop bulky lethal tumors by age 24 weeks of age
|
|
|
• at generations 3 and 4 (G3/4), all develop invasive prostate adenocarcinomas by 24 weeks of age
|
|
|
• at G3/4, high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
|
• at generations 3 and 4 (G3/4), all develop invasive prostate adenocarcinomas by 24 weeks of age
|
|
|
• at G3/4, high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
• in some (5 of 20) G3/4 mice lumbar spine metastases are seen unlike in G0 mice
|
|
|
• at generations 3 and 4 (G3/4), all develop invasive prostate adenocarcinomas by 24 weeks of age
|
|
|
• at G3/4, high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age
|
|
• increase in the number of chromosomal aberrations in tumor cells from G3/4 mice compared to G0 mice
|
|
• increased length in prostate tumor cells compared to G3/4 mice homozygous for Terttm1Rdp, Ptentm1Rdp and Trp53tm1Brn and hemizygous for Tg(Pbsn-cre)4Prb
|
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:186105 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.4 months of age and no distant metastases are seen
|
|
• mice develop intestinal adenocarcinomas with a median tumor-free survival of 5.4 months of age and no distant metastases are seen
|
|
|
| ♀ | 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 29 weeks after ad-cre inoculation
|
|
• mice inoculated with ad-cre exhibit a high frequency of fatal pulmonary hemorrhage
|
|
• mice inoculated with ad-cre exhibit a high frequency of fatal pulmonary hemorrhage
|
|
• some ad-cre inoculated mice develop lung tumors with low tumor multiplicity
|
|
• some ad-cre inoculated mice develop lung tumors with low tumor multiplicity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 73% of mice develop malignant gliomas consisting of anaplastic astrocytomas (in 66% of mice with tumors) and glioblastomas (in 34% of mice with tumors)
|
|
• 34% of mice with tumors develop glioblastomas
|
|
• anaplastic astrocytomas (in 66% of mice with tumors)
|
|
• 73% of mice develop malignant gliomas consisting of anaplastic astrocytomas (in 66% of mice with tumors) and glioblastomas (in 34% of mice with tumors)
|
|
• 34% of mice with tumors develop glioblastomas
|
|
• anaplastic astrocytomas (in 66% of mice with tumors)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age
|
|
• 35.7% of mice show lung metastasis
|
|
• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age
|
|
• mice develop mammary gland carcinoma with a median tumor-free survival of 12.1 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenoviral cre treatment, 2 of 13 mice develop malignant mesotheliomas-like thoracic tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenoviral cre treatment, 40% of mice develop thoracic tumors (including malignant mesotheliomas, 5 of 20; and schwannomas, 3 of 20) with a longer latency than in mice homozygous for all alleles
• following adenoviral cre treatment, one mouse developed hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus
• following adenoviral cre treatment, 2% of mice develop aspecific tumors not induced by adeno-cre treatment
|
|
• following adenoviral cre treatment, 1 mouse developed hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus
|
|
• following adenoviral cre treatment, 1 mouse developed hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenoviral cre treatment, median survival time is 215 days
|
|
• following adenoviral cre treatment, 62% of mice develop thoracic tumors (including malignant mesothelimas, 20 of 34; and schwannomas, 1 of 34) with a longer latency than in mice homozygous for all alleles
• following adenoviral cre treatment, 21% of mice develop aspecific tumors not induced by adeno-cre treatment
|
|
|
• in 9% of mice following adenoviral cre treatment
|
|
• following adenoviral cre treatment, 9% of mice develop monocytic myeloid leukemias
|
|
|
• in 9% of mice following adenoviral cre treatment
|
|
|
• in 9% of mice following adenoviral cre treatment
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenoviral cre treatment, median survival time is 135 days
|
|
• following adenoviral cre treatment, 86% of mice develop thoracic tumors (including malignant mesotheliomas, 45 of 55; rhabdomyosarcomas, 2 of 55; and schwannomas, 1 of 55)
• following adenoviral cre treatment, mice develop either non-aggressive epitheloid or mixed tumors with confined invasion of the visceral pleural or (sarcomatoid) tumors with strong invasion of visceral and parietal pleura
• following adenoviral cre treatment, 4% of mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus
• following adenoviral cre treatment, 11% of mice develop aspecific tumors not induced by adeno-cre treatment
• following adenoviral cre treatment, latency to developing malignant mesotheliomas is lower than in mice carrying other combinations of Cdkn2atm2Brn, Nf2tm2Gth, and Trp53tm1Brn alleles
|
|
• a few following adenoviral cre treatment
|
|
|
• in 7% of mice following adenoviral cre treatment
|
|
• following adenoviral cre treatment, 7% mice develop monocytic myeloid leukemias
|
|
• following adenoviral cre treatment, latency to developing malignant mesotheliomas is lower than in mice carrying other combinations of Cdkn2atm2Brn, Nf2tm2Gth, and Trp53tm1Brn alleles
|
|
• following adenoviral cre treatment, 4% of mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus
|
|
|
• in 7% of mice following adenoviral cre treatment
|
|
• a few following adenoviral cre treatment
|
|
• following adenoviral cre treatment, 4% of mice develop hepatomegaly either due to oval cell hyperplasia, cholangio-carcinomas and/or hepatomas, and leiomyomas of the uterus
|
|
|
• in 7% of mice following adenoviral cre treatment
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant mesothelioma | DOID:1790 |
OMIM:156240 |
J:132943 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenoviral cre treatment, median survival time is 80 days
|
|
• following adenoviral cre treatment, 100% of mice develop highly invasive thoracic tumors (including malignant mesotheliomas, 47 of 51; rhabdomyosarcomas, 4 of 51; and schwannomas, 1 of 51)
• following adenoviral cre treatment, 75% of mice develop of aggressive malignant mesotheliomas at a shorter latency than in mice carrying other combinations of Cdkn2atm2Brn, Nf2tm2Gth, and Trp53tm1Brn alleles
|
|
• following adenoviral cre treatment, 75% of mice develop of aggressive malignant mesotheliomas at a shorter latency than in mice carrying other combinations of Cdkn2atm2Brn, Nf2tm2Gth, and Trp53tm1Brn alleles
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant mesothelioma | DOID:1790 |
OMIM:156240 |
J:132943 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adenoviral cre treatment, the parietal pleura often shows invasion with concomitant pleural effusion
|
|
• following adenoviral cre treatment, 94% of mice develop aggressive thoracic tumors (including malignant mesotheliomas, 15 of 51; and rhabdomyosarcomas, 1 of 51) with the parietal pleura often showing invasion with concomitant pleural effusion
• following adenoviral cre treatment, 1% of mice develop aspecific tumors not induced by adeno-cre treatment
|
|
• following adenoviral cre treatment, the parietal pleura often shows invasion with concomitant pleural effusion
|
|
• following adenoviral cre treatment, the parietal pleura often shows invasion with concomitant pleural effusion
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant mesothelioma | DOID:1790 |
OMIM:156240 |
J:132943 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• ovarian tumors are seen in 3-12 month old mice
• tumors are bilateral and larger than those of Kit homozygous mutants and are almost entirely positive for cytokeratin 8, suggesting epithelial origin and show active proliferation
|
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
|
• ovarian tumors are seen in 3-12 month old mice
• tumors are bilateral and larger than those of Kit homozygous mutants and are almost entirely positive for cytokeratin 8, suggesting epithelial origin and show active proliferation
|
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
|
• ovarian tumors are seen in 3-12 month old mice
• tumors are bilateral and larger than those of Kit homozygous mutants and are almost entirely positive for cytokeratin 8, suggesting epithelial origin and show active proliferation
|
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
|
• about 50% of ovaries contain mixed epithelial and granulosa tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival is 13 months, with none surviving beyond 18 months
• lethality before 1 year is unrelated to cancer as no tumors are seen until after 1 year of age
|
|
• mice that survive beyond 1 year of age develop skin tumors
• less than 1/4 of mice develop more than a single tumor
|
|
• mice form mostly basal cell carcinomas
|
|
• mice that survive beyond 1 year of age develop skin tumors
• less than 1/4 of mice develop more than a single tumor
|
|
• mice form mostly basal cell carcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| basal cell carcinoma | DOID:2513 | J:216813 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival is 9 months
|
|
• loss of fur by the 5th week of age, with mice nearly devoid of fur and whiskers by 12 weeks of age
|
|
• dysmorphic hair follicles with dyskertotic cells in the follicular epithelium
• regions of increased cellularity with many mitotic figures are seen in the interfollicular epidermal layer and above the basal layer
• large amount of DNA damage in the basal layer of follicular epithelium and in the interfollicular epidermis
• there is some evidence of attempts to form new follicles
|
|
• at a time when control hair follicles are in the telogen phase of the hair cycles, mutants show anagen growth phase hairs with dysmorphic follicles, abnormal hair shafts, and dyskertotic cells in the follicular epithelium
|
|
• pre-malignant basaloid proliferation is seen
|
|
• increase in thickness of the epidermis with a mean thickness of 51.3 um compared to 24 um in controls
|
|
• mice develop highly aggressive and numerous skin tumors starting at 7-8 months of age with all mice showing skin tumors by 12-15 months of age
• 41% of mice form multiple tumors
|
|
• mice form moderately or poorly differentiated squamous cell carcinomas and nearly half of mutants develop poorly differentiated carcinomas
• poorly or undifferentiated carcinomas are highly invasive
|
|
• the number of apoptotic cells in the epidermis is lower than in single conditional Dicer1 mutants
• increase in the numbers of mitotic cells in the epidermis, indicating increased proliferation
|
|
• mice develop highly aggressive and numerous skin tumors starting at 7-8 months of age with all mice showing skin tumors by 12-15 months of age
• 41% of mice form multiple tumors
|
|
• mice form moderately or poorly differentiated squamous cell carcinomas and nearly half of mutants develop poorly differentiated carcinomas
• poorly or undifferentiated carcinomas are highly invasive
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| squamous cell carcinoma | DOID:1749 | J:216813 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die due to tumors not heart failure
|
|
• mice show an extended mean survival of 403 days compared to compound heterozygous Mdm4tm2Glo/Mdm4tm2.1Glo conditional mutants
|
| N |
• mice do not exhibit signs of heart failure such as edema and poor breathing and exhibit rescue of the dilated cardiomyopathy
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 3 months of age, all mice develop WNT-subgroup medulloblastomas
|
|
• by 3 months of age, all mice develop WNT-subgroup medulloblastomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 11 months, 4% of mice develop WNT-subgroup medulloblastomas
|
|
• by 11 months, 4% of mice develop WNT-subgroup medulloblastomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the spleen but not as severe as in Atmintm1.2Jhh/Atmintm1.2Jhh Cd79atm1(cre)Reth/Cd79a+ mice
|
|
• in the bone marrow but not as severe as in Atmintm1.2Jhh/Atmintm1.2Jhh Cd79atm1(cre)Reth/Cd79a+ mice
|
|
• in the spleen but not as severe as in Atmintm1.2Jhh/Atmintm1.2Jhh Cd79atm1(cre)Reth/Cd79a+ mice
|
|
• in the bone marrow but not as severe as in Atmintm1.2Jhh/Atmintm1.2Jhh Cd79atm1(cre)Reth/Cd79a+ mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop mammary gland with a latency of 213 days
• 80% of mice develop tumors compared to 63% of Trp53tm1Jjon/Trp53tm1Jjon Tg(KRT14-cre)8Jjon mice
• mice develop mammary types of carcinoma (91%), biphasic carcinoma that is poorly defined (3%) and biphasic carcinoma that is well defined (6%)
|
|
• mice develop mammary gland with a latency of 213 days
• 80% of mice develop tumors compared to 63% of Trp53tm1Jjon/Trp53tm1Jjon Tg(KRT14-cre)8Jjon mice
• mice develop mammary types of carcinoma (91%), biphasic carcinoma that is poorly defined (3%) and biphasic carcinoma that is well defined (6%)
|
|
• mice develop mammary gland with a latency of 213 days
• 80% of mice develop tumors compared to 63% of Trp53tm1Jjon/Trp53tm1Jjon Tg(KRT14-cre)8Jjon mice
• mice develop mammary types of carcinoma (91%), biphasic carcinoma that is poorly defined (3%) and biphasic carcinoma that is well defined (6%)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:126551 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop mammary gland with a latency of 332 days
|
|
• mice develop mammary gland with a latency of 332 days
|
|
• mice develop mammary gland with a latency of 332 days
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:126551 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop mammary gland with a latency of 407 days
|
|
• mice develop mammary gland with a latency of 407 days
|
|
• mice develop mammary gland with a latency of 407 days
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:126551 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups born alive die between P1 and P2
• however, most pups do survive to birth unlike in mutant mice wild-type for Trp53
|
|
• asymmetric and abnormal development of the lower jaw
|
|
• at E18.5
|
|
• at E18.5
|
|
• asymmetric and abnormal development of the lower jaw
|
|
• at E18.5
|
|
• reduced ossification of the frontal bone
|
|
• at E18.5
|
|
• at E18.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no reduction in craniofacial defects in conditional double mutant embryos at E10.5 and E17.5 compared to mutant embryos with wild-type levels of Trp53
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• rescue of the CD4+CD8+ double positive thymocyte developmental defect
• significant increase in the number of single positive thymocytes in comparison to mutant mice wild-type for Trp53
• significant recovery of DN3L cells close to levels in control mice
• significant increase in the number of late pro-B cells in comparison to mutant mice wild-type for Trp53
|
|
• numbers of pre-B (IgM+B220+CD19+CD43-) are not increased by the absence of Trp53 expression
|
|
• numbers of pre-B (IgM+B220+CD19+CD43-) are not increased by the absence of Trp53 expression
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• incidence is decreased compared to mutant mice wild-type for Runx3
|
|
• increased lifespan compared to mutant mice wild-type for Runx3
|
|
• incidence is decreased compared to mutant mice wild-type for Runx3
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased incidence compared to mutant mice wild-type for Runx3
|
|
• increased lifespan compared to mutant mice wild-type for Runx3
|
|
• decreased incidence compared to mutant mice wild-type for Runx3
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time is increased compared to mutant mice wild-type for Rr420
|
|
• decreased incidence compared to mutant mice wild-type for Rr420
• decrease is similar to mutant osteosarcoma model mice homozygous for Runx3tm1.1Itok
|
|
• decreased incidence compared to mutant mice wild-type for Rr420
• decrease is similar to mutant osteosarcoma model mice homozygous for Runx3tm1.1Itok
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival time is increased compared to mutant mice wild-type for Rr420
|
|
• decreased incidence compared to mutant mice wild-type for Rr420
• decrease is similar to mutant osteosarcoma model mice homozygous for Runx3tm1.1Itok
|
|
• decreased incidence compared to mutant mice wild-type for Rr420
• decrease is similar to mutant osteosarcoma model mice homozygous for Runx3tm1.1Itok
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop osteosarcoma with a mean latency of 226.5 days
• 25% of tumors are found on the mandible/head, 50% of tumors are found on the lower long bones, and 25% of tumors are in other axial locations
• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma
|
|
• mutants have a median survival of 226.5 days of age
|
|
• 50% of mice show metastatic dissemination, commonly to the lung and liver
|
|
• mutants develop osteosarcoma with a mean latency of 226.5 days
• 25% of tumors are found on the mandible/head, 50% of tumors are found on the lower long bones, and 25% of tumors are in other axial locations
• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:199542 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop neoplastic lesions from both vascular (40.5%) and hematopoietic origins (54.8%), mainly T-cell lymphomas, at an average age of 25.5 weeks
|
|
• mice develop neoplastic lesions from both vascular (40.5%) and hematopoietic origins (54.8%), mainly T-cell lymphomas, at an average age of 25.5 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop tumors after 15.5 weeks of age, with a complete shift towards hematopoietic neoplastic lesions (100%), mainly precursor T-cell lymphoma (85.7%)
• T-cell antigen receptor rearrangement analysis suggests either mono- or oligoclonal origin for all the thymic tumors
|
|
• mice develop tumors after 15.5 weeks of age, with a complete shift towards hematopoietic neoplastic lesions (100%), mainly precursor T-cell lymphoma (85.7%)
• T-cell antigen receptor rearrangement analysis suggests either mono- or oligoclonal origin for all the thymic tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop tumors after 12.7 weeks of age, with a complete shift towards hematopoietic neoplastic lesions (100%), mainly precursor T-cell lymphoma (87.5%)
• cell antigen receptor rearrangement analysis suggests either mono- or oligoclonal origin for all the thymic tumors
|
|
• thymomas have an immature/early T-cell precursor leukemia signature
• 12.5% of tumors are myeloid leukemia
|
|
• thymomas have an immature/early T-cell precursor leukemia signature
• thymic tumors lack mature T-cell markers such as surface CD3 and CD8 and exhibit a higher percentage of cells that express the stem/progenitor marker cKit or CD44
|
|
• mice develop tumors after 12.7 weeks of age, with a complete shift towards hematopoietic neoplastic lesions (100%), mainly precursor T-cell lymphoma (87.5%)
• cell antigen receptor rearrangement analysis suggests either mono- or oligoclonal origin for all the thymic tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice die before 3 weeks
|
|
• slightly less so than in Gt(ROSA)26Sortm1(Gck)Ydor/Gt(ROSA)26Sor+ Tg(Ins2-cre)25Mgn mice
|
| N |
• islet architecture and beta cells are preserved in newborns
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
High-grade prostate intraepithelial neoplasia in Brca2tm1Brn/Brca2tm1Brn Tg(Pbsn-cre)4Prb/0 Trp53tm1Brn/Trp53tm1Brn and prostate hyperplasia and intraepithelial neoplasia in Brca2tm1Brn/Brca2tm1Brn Trp53tm1Brn/Trp53+ Tg(Pbsn-cre)4Prb/0 mice
|
|
• focal low grade PIN are seen at 10 - 14 months of age
• by 15 - 20 months of age both focal low grade and high grade PIN are seen
• the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele
• levels of cell proliferation are 9 fold higher in PIN lesions
|
|
|
• focal hyperplasia is seen beginning at 10 -14 months of age
|
|
|
• focal low grade PIN are seen at 10 - 14 months of age
• by 15 - 20 months of age both focal low grade and high grade PIN are seen
• the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele
• levels of cell proliferation are 9 fold higher in PIN lesions
|
|
|
• areas of hyperplasia are positive for markers of DNA damage
• 4 fold increase in apoptotic cells in PIN foci
|
|
|
• focal hyperplasia is seen beginning at 10 -14 months of age
|
|
|
• focal low grade PIN are seen at 10 - 14 months of age
• by 15 - 20 months of age both focal low grade and high grade PIN are seen
• the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele
• levels of cell proliferation are 9 fold higher in PIN lesions
|
|
|
• areas of hyperplasia are positive for markers of DNA damage
• 4 fold increase in apoptotic cells in PIN foci
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
High-grade prostate intraepithelial neoplasia in Brca2tm1Brn/Brca2tm1Brn Tg(Pbsn-cre)4Prb/0 Trp53tm1Brn/Trp53tm1Brn and prostate hyperplasia and intraepithelial neoplasia in Brca2tm1Brn/Brca2tm1Brn Trp53tm1Brn/Trp53+ Tg(Pbsn-cre)4Prb/0 mice
|
|
• by 10 - 14 months of age both focal low grade and high grade PIN are seen
• the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele
• frequently multiple ducts of each lobe have high grade PIN, which are present in proximal and distal regions of the prostate and consist of many atypical cells filling
the lumen
• high grade PIN lesions are predominantly seen in the anterior and dorsal prostate
• levels of cell proliferation are 30 fold higher in PIN lesions
• high grade PIN lesions frequently contain large groups of basal cells some of which are rounder in shape and positioned near the lumen
• high grade lesions continue to proliferate post castration
|
|
|
• focal hyperplasia is seen beginning as early as 6 months of age
|
|
|
• by 10 - 14 months of age both focal low grade and high grade PIN are seen
• the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele
• frequently multiple ducts of each lobe have high grade PIN, which are present in proximal and distal regions of the prostate and consist of many atypical cells filling
the lumen
• high grade PIN lesions are predominantly seen in the anterior and dorsal prostate
• levels of cell proliferation are 30 fold higher in PIN lesions
• high grade PIN lesions frequently contain large groups of basal cells some of which are rounder in shape and positioned near the lumen
• high grade lesions continue to proliferate post castration
|
|
|
• areas of hyperplasia are positive for markers of DNA damage
• 20 fold increase in apoptotic cells in areas of high grade PIN
|
|
|
• focal hyperplasia is seen beginning as early as 6 months of age
|
|
|
• by 10 - 14 months of age both focal low grade and high grade PIN are seen
• the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele
• frequently multiple ducts of each lobe have high grade PIN, which are present in proximal and distal regions of the prostate and consist of many atypical cells filling
the lumen
• high grade PIN lesions are predominantly seen in the anterior and dorsal prostate
• levels of cell proliferation are 30 fold higher in PIN lesions
• high grade PIN lesions frequently contain large groups of basal cells some of which are rounder in shape and positioned near the lumen
• high grade lesions continue to proliferate post castration
|
|
|
• areas of hyperplasia are positive for markers of DNA damage
• 20 fold increase in apoptotic cells in areas of high grade PIN
|
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:161511 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by 20 weeks of age of unknown cause
|
|
• all mice develop malignant carcinomas in the oral cavity or lips by 18 weeks of age
• tumors are similar to those that develop in Trp53tm1Brn/Trp53tm1Brn Tg(KRT14-cre)8Brn Tg(KRT5-Akt1*)Jmpa mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• proliferation is increased in oral tumors compared to in Tg(KRT5-Akt1*)Jmpa oral tumors
• the number of blood vessels is enhanced in dysplasias and tumors compared to normal oral epithelia in Tg(KRT5-Akt1*)Jmpa mice
|
|
• mice develop malignant carcinomas in the oral cavity affecting the palate, ventral side of the tongue, and the external and internal sides of the lips unlike in wild-type mice
• mice develop tumors earlier than in mice expressing Trp53
• mice develop lymph node metastases and lung micrometastases from undifferentiated highly aggressive primary tumors
|
|
• cell proliferation of nonlesion oral epithelia is greater than in wild-type and Tg(KRT5-Akt1*)Jmpa mice
|
|
• oral keratinocyte proliferation is greater than in wild-type cells
|
|
• oral keratinocyte proliferation is greater than in wild-type cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| head and neck squamous cell carcinoma | DOID:5520 |
OMIM:275355 |
J:144831 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 78% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• 78% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• 78% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:189304 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 88% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• 88% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
|
|
• 88% of mice injected with a cre-expressing adenovirus under the bursa develop serous epithelial ovarian cancer pathology
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:189304 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal bladder morphology and vascularization
|
| N |
• mice exhibit normal bladder vascularization
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females develop mammary tumors with a latency of 11.3 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 72% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
|
|
• about 72% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer
|
|
|
• 17% of mammary tumors are adenomyoepithelioma
|
|
|
• females develop mammary tumors with a latency of 11.3 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 72% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
|
|
• females develop mammary tumors with a latency of 11.3 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 72% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:224955 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females develop mammary tumors with a latency of 16.9 months
|
|
|
• 30% of mammary tumors are mixed mesenchymal adenocarcinomas and 10% are adenosquamous carcinoma
|
|
|
• about 30% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer
|
|
|
• 30% of mammary tumors are adenomyoepithelioma
|
|
|
• females develop mammary tumors with a latency of 16.9 months
|
|
|
• 30% of mammary tumors are mixed mesenchymal adenocarcinomas and 10% are adenosquamous carcinoma
|
|
|
• females develop mammary tumors with a latency of 16.9 months
|
|
|
• 30% of mammary tumors are mixed mesenchymal adenocarcinomas and 10% are adenosquamous carcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 of 23 mice develop anaplastic astrocytomas
|
|
• 4 of 23 mice develop anaplastic astrocytomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females develop mammary tumors with a latency of 9.8 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 67% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
|
|
• about 67% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer
|
|
|
• 11% of mammary tumors are adenomyoepithelioma
|
|
|
• females develop mammary tumors with a latency of 9.8 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 67% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
|
|
• females develop mammary tumors with a latency of 9.8 months
• expression analysis indicates that mammary tumors resemble human claudin-low triple-negative-like breast cancer and show more mesenchymal features
|
|
|
• about 67% of tumors are classified as adeno-sacromatoid/spindle-cell/mesenchymal-like breast cancer, with the rest showing mixed mesenchymal plus adenocarcinomas or differentiated adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:224955 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with an adenovirus-expressing Cre recombinase (Ad-Cre) into the ovarian bursa at 2 months of age exhibit enhanced growth of ovarian tumors compared to single homozygous Kit mutants, however, no metastasis or spreading of the tubular adenomas is seen in most mice
• tumors in Ad-Cre injected mice are largely epithelial in origin and similar to human serous ovarian cancer
• 3 of 12 mice injected with Ad-Cre into the ovarian bursa develop aggressive tumors
|
|
• mice injected with Ad-Cre into the ovarian bursa show ovaries that commonly contain cysts of hemorrhage appearance
|
|
• mice injected with an adenovirus-expressing Cre recombinase (Ad-Cre) into the ovarian bursa at 2 months of age exhibit enhanced growth of ovarian tumors compared to single homozygous Kit mutants, however, no metastasis or spreading of the tubular adenomas is seen in most mice
• tumors in Ad-Cre injected mice are largely epithelial in origin and similar to human serous ovarian cancer
• 3 of 12 mice injected with Ad-Cre into the ovarian bursa develop aggressive tumors
|
|
• ovarian epithelial cells show enhanced cell proliferation in culture compared to single homozygous Kit mutants
|
|
• mice injected with Ad-Cre into the ovarian bursa show ovaries that commonly contain cysts of hemorrhage appearance
|
|
• mice injected with an adenovirus-expressing Cre recombinase (Ad-Cre) into the ovarian bursa at 2 months of age exhibit enhanced growth of ovarian tumors compared to single homozygous Kit mutants, however, no metastasis or spreading of the tubular adenomas is seen in most mice
• tumors in Ad-Cre injected mice are largely epithelial in origin and similar to human serous ovarian cancer
• 3 of 12 mice injected with Ad-Cre into the ovarian bursa develop aggressive tumors
|
|
• ovarian epithelial cells show enhanced cell proliferation in culture compared to single homozygous Kit mutants
|
|
• mice injected with Ad-Cre into the ovarian bursa show ovaries that commonly contain cysts of hemorrhage appearance
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:236161 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared to KB1C61GP littermate controls
• most mammary tumors are poorly differentiated solid carcinomas
• a small percentage of tumors are classified as carcinosarcomas or lumen forming carcinomas
|
|
• compared to KB1C61GP littermate controls
|
|
• in transplanted tumors response to olaparib treatment is improved compared to KB1C61GP littermate controls and KP mice
• transplanted tumors never develop resistance to cisplatin unlike tumors from KP mice
|
|
• increased genomic instability in tumors compared to mice homozygous for Trp53tm1Brn and carrying Tg(KRT14-cre)8Brn (KP mice)
|
|
• median latency is 236 days compared to 197 days in littermate controls heterozygous for Brca1tm1Brn and Brca1tm1.1Jjon, homozygous for Trp53tm1Brn and carrying Tg(KRT14-cre)8Brn (KB1C61GP)
|
|
• compared to KB1C61GP littermate controls
• most mammary tumors are poorly differentiated solid carcinomas
• a small percentage of tumors are classified as carcinosarcomas or lumen forming carcinomas
|
|
• compared to KB1C61GP littermate controls
|
|
• compared to KB1C61GP littermate controls
• most mammary tumors are poorly differentiated solid carcinomas
• a small percentage of tumors are classified as carcinosarcomas or lumen forming carcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:178595 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared to KB1P littermate controls homozygous
• most mammary tumors are poorly differentiated solid carcinomas
• a small percentage of tumors are classified as carcinosarcomas or lumen forming carcinomas
|
|
• markedly lower incidence compared to KB1P littermate controls
|
|
• in transplanted tumors response to olaparib treatment is impaired compared to KB1P littermate controls but better than in KP mice
• transplanted tumors develop resistance to cisplatin and survival of transplanted mice is worse than that of mice transplanted with tumors from KB1P mice
|
|
• increased genomic instability in tumors compared to mice homozygous for Trp53tm1Brn and carrying Tg(KRT14-cre)8Brn (KP mice)
|
|
• median latency is 197 days compared to 236 days in littermate controls homozygous for Brca1tm1Brn Trp53tm1Brn and carrying Tg(KRT14-cre)8Brn (KB1P)
• however, no difference in the latency of mammary tumor development
|
|
• compared to KB1P littermate controls homozygous
• most mammary tumors are poorly differentiated solid carcinomas
• a small percentage of tumors are classified as carcinosarcomas or lumen forming carcinomas
|
|
• markedly lower incidence compared to KB1P littermate controls
|
|
• compared to KB1P littermate controls homozygous
• most mammary tumors are poorly differentiated solid carcinomas
• a small percentage of tumors are classified as carcinosarcomas or lumen forming carcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:178595 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• adenocarcinomas (serous and clear cell) show KPNA2 expression while endometrial intraepithelial carcinomas and endometrial glandular dysplasia foci do not exhibit KPNA2 overexpression
(J:214850)
• mice show endometrial alterations that progress from normal epithelium to endometrial glandular dysplasia, to endometrial intraepithelial carcinoma, and finally to a papillary adenocarcinoma
(J:215149)
• 16 of 19 females at 65-67 weeks of age develop endometrial tumors; three different histological subtypes of type II endometrial carcinomas, as well as carcinosarcomas, develop at high frequency
(J:215149)
• individual mice frequently exhibit multiple independent endometrial tumors of different histological appearances
(J:215149)
• adenocarcinomas with a papillary growth pattern form exclusively from the surface epithelium of the lumen, whereas those with an acinar growth pattern arise from endometrial glands; both are either serous or clear cell adenocarcinomas
(J:215149)
• an intermediate lesion, microinvasive adenocarcinoma, is seen in the glandular compartment of the endometrium
(J:215149)
• the lumen surface epithelium also shows sites of endometrial intraepithelial carcinoma with papillary structures lesion characterized by a papillary growth pattern with fibrovascular core
(J:215149)
|
|
|
• all mice at 24-29 weeks of age show some regions of endometrial glandular dysplasia which are characterized by enlarged and hyperchromatic nuclei, prominent nucleoli, nuclear crowding and loss of basal nuclear localization
|
|
|
• regions of the epithelium of the corpus epididymis of males frequently develop a vacuolated appearance and display nuclear atypia at around 6 months of age; these lesions do not progress to tumors
|
|
|
• adenocarcinomas (serous and clear cell) show KPNA2 expression while endometrial intraepithelial carcinomas and endometrial glandular dysplasia foci do not exhibit KPNA2 overexpression
(J:214850)
• mice show endometrial alterations that progress from normal epithelium to endometrial glandular dysplasia, to endometrial intraepithelial carcinoma, and finally to a papillary adenocarcinoma
(J:215149)
• 16 of 19 females at 65-67 weeks of age develop endometrial tumors; three different histological subtypes of type II endometrial carcinomas, as well as carcinosarcomas, develop at high frequency
(J:215149)
• individual mice frequently exhibit multiple independent endometrial tumors of different histological appearances
(J:215149)
• adenocarcinomas with a papillary growth pattern form exclusively from the surface epithelium of the lumen, whereas those with an acinar growth pattern arise from endometrial glands; both are either serous or clear cell adenocarcinomas
(J:215149)
• an intermediate lesion, microinvasive adenocarcinoma, is seen in the glandular compartment of the endometrium
(J:215149)
• the lumen surface epithelium also shows sites of endometrial intraepithelial carcinoma with papillary structures lesion characterized by a papillary growth pattern with fibrovascular core
(J:215149)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| endometrial cancer | DOID:1380 |
OMIM:608089 |
J:214850 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by 20 months of age
|
| N |
• mice exhibit a normal fur coat at they age
|
|
• mice develop spontaneous carcinomas; half of tumors are well-differentiated squamous cell carcinomas, a few are moderately differentiated and poorly differentiated squamous cell carcinomas
• less than 1/4 of mice develop more than a single tumor
|
|
• mice develop spontaneous carcinomas; half of tumors are well-differentiated squamous cell carcinomas, a few are moderately differentiated and poorly differentiated squamous cell carcinomas
• less than 1/4 of mice develop more than a single tumor
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in mice with wild-type Coro1c in tamoxifen-treated mice
|
|
• as in mice with wild-type Coro1c in tamoxifen-treated mice
|
|
• as in mice with wild-type Coro1c in tamoxifen-treated mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• ~50% reduction in eye volume at age P7
|
|
• at age P13
|
|
• at age P13
|
|
• dysregulated DNA damage response (DDR) of lens progenitor cells in E15.5 embryos
• normal cell cycle and proportion of mitotic cells of lens progenitor cells in E15.5 embryos
• no lens epithelium apoptosis in E15.5 embryos
|
|
• increased number of mitotic defects in lens progenitor cells in E15.5 embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• neuronal apoptosis observed in Tubb5tm2.1Dak / Tubb5+ Tg(Nes-cre)1Kln mice is rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• bone marrow B cell development and stimulated and unstimulated splenic B cell proliferation are restored compared to in Cd79atm1(cre)Reth/Cd79a+ Huwe1tm1.1Mak/Y mice
|
|
|
• to a greater extent than in Cd79atm1(cre)Reth/Cd79a+ Huwe1tm1.1Mak/Y mice following stimulation of B cells with LPS or LPS plus IL4
|
|
|
• virtually absent in the peritoneal cavity
|
|
|
• to a greater extent than in Cd79atm1(cre)Reth/Cd79a+ Huwe1tm1.1Mak/Y mice following stimulation of B cells with LPS or LPS plus IL4
|
|
|
• virtually absent in the peritoneal cavity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice have similar levels of apoptosis in the cerebella as Rb1, Rbl1 double mutants which express Trp53
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• sebaceous gland carcinoma
|
|
• mice develop skin tumors more rapidly than single Tg(KRT14-Snai1)1Efu expressing mice, with a median latency of 176 days
• however, mice do not develop more tumors than Tg(KRT14-Snai1)1Efu mice alone
• tumors include basal cell carcinoma, squamous cell carcinoma, and sebaceous gland carcinoma and more aggressive carcinosarcomas characterized by the biphasic appearance of intermixed epithelial and mesenchymal elements
|
|
• sebaceous gland carcinoma
|
|
• mice develop skin tumors more rapidly than single Tg(KRT14-Snai1)1Efu expressing mice, with a median latency of 176 days
• however, mice do not develop more tumors than Tg(KRT14-Snai1)1Efu mice alone
• tumors include basal cell carcinoma, squamous cell carcinoma, and sebaceous gland carcinoma and more aggressive carcinosarcomas characterized by the biphasic appearance of intermixed epithelial and mesenchymal elements
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3 of 21 mice develop mammary gland tumors with a latency of 21 months unlike wild-type mice
|
|
|
• at 12 months fewer alveoli are found within the mammary glands compared to in wild-type mice
|
|
• 3 of 21 mice develop mammary gland tumors with a latency of 21 months unlike wild-type mice
|
|
|
• at 12 months fewer alveoli are found within the mammary glands compared to in wild-type mice
|
|
• 3 of 21 mice develop mammary gland tumors with a latency of 21 months unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• extensive with patches of reduced angiogenesis
|
|
• 20 of 33 mice develop mammary gland tumors with a median latency of 10.5 months unlike wild-type mice
|
|
• tumors are more complex than in Trp53tm1Brn Tg(MMTV-cre)Mam homozygotes
• tumors exhibit aneuploidy and chromosomal aberrations
|
|
• in tumors
|
|
• in tumors
|
|
• extensive with patches of reduced angiogenesis
|
|
|
• at 12 months, mammary glands exhibit increased branching morphogenesis and hyperplastic foci compared to in wild-type mice
|
|
|
• at 12 months fewer alveoli are found within the mammary glands compared to in wild-type mice
|
|
• 20 of 33 mice develop mammary gland tumors with a median latency of 10.5 months unlike wild-type mice
|
|
|
• starting at 12 months, mammary glands exhibit hyperplastic and non-invasive focal lesions unlike wild-type mice
|
|
|
• at 12 months, mammary glands exhibit increased branching morphogenesis and hyperplastic foci compared to in wild-type mice
|
|
|
• at 12 months fewer alveoli are found within the mammary glands compared to in wild-type mice
|
|
• 20 of 33 mice develop mammary gland tumors with a median latency of 10.5 months unlike wild-type mice
|
|
|
• starting at 12 months, mammary glands exhibit hyperplastic and non-invasive focal lesions unlike wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mammary glands do not exhibit hyperplastic foci
|
|
• tumors are more complex than in Trp53tm1Brn Tg(MMTV-cre)Mam homozygotes
|
|
• mice develop fewer tumors than in Trp53tm1Brn Tg(MMTV-cre)Mam homozygotes
|
|
|
• at 12 months fewer alveoli are found within the mammary glands compared to in wild-type mice
|
|
|
• at 12 months fewer alveoli are found within the mammary glands compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumors are less complex than in mice with one or two Chek1tm2.1Sje alleles
|
|
• mice exhibit increased tumor incidence compared to in mice with one or two Chek1tm2.1Sje alleles
|
|
• in 5 of 10 mouse at 8 months of age
• in 1 of 10 mouse at 13 months of age
|
|
• in 4 of 10 mouse at 7 to 8 months of age
|
|
• in 5 of 10 mouse at 8 months of age
• in 1 of 10 mouse at 13 months of age
|
|
• in 5 of 10 mouse at 8 months of age
• in 1 of 10 mouse at 13 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 7 of 11 mice develop mammary gland tumors with a latency of 9 months unlike wild-type mice
|
|
• mice develop fewer tumors than in Trp53tm1Brn Tg(MMTV-cre)Mam homozygotes
|
|
|
• at 12 months fewer alveoli are found within the mammary glands compared to in wild-type mice
|
|
• 7 of 11 mice develop mammary gland tumors with a latency of 9 months unlike wild-type mice
|
|
|
• mammary glands exhibit multifocal hyperplasia unlike in wild-type mice that are more uniform than in Chek1tm2.1Sje Trp53tm1Brn Tg(MMTV-cre)Mam heterozygotes
|
|
|
• at 12 months fewer alveoli are found within the mammary glands compared to in wild-type mice
|
|
• 7 of 11 mice develop mammary gland tumors with a latency of 9 months unlike wild-type mice
|
|
|
• mammary glands exhibit multifocal hyperplasia unlike in wild-type mice that are more uniform than in Chek1tm2.1Sje Trp53tm1Brn Tg(MMTV-cre)Mam heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop tumors with a short median latency period of 298 days
• tumors exhibit expansive growth pattern, a high nuclear grade, and a high mitotic index
|
|
• in 55% of mice
|
|
• mice develop skin carcinomas
|
|
• in 55% of mice
|
|
• mice develop skin carcinomas
|
|
• in 55% of mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma
• females also develop solid carcinoma/carcinosarcoma that predominantly exhibit a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns
|
|
|
• pups show reduced survival rates due to inhibition or absence of lactation
|
|
|
• mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma
• females also develop solid carcinoma/carcinosarcoma that predominantly exhibit a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns
|
|
|
• pups show reduced survival rates due to inhibition or absence of lactation
|
|
|
• mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma
• females also develop solid carcinoma/carcinosarcoma that predominantly exhibit a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns
|
|
|
• 70% of females that present mammary tumors of about 1 cm show extensive local invasion and metastases to draining and distant lymph nodes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• females develop mammary tumors with a median latency of around 290 days
• mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma
• virgin females develop mammary tumors with identical incidence and latency as uniparous females
• tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females
|
|
|
• some mice develop intermediate-grade adenocarcinoma
|
|
|
• females develop mammary tumors with a median latency of around 290 days
• mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma
• virgin females develop mammary tumors with identical incidence and latency as uniparous females
• tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females
|
|
|
• some mice develop intermediate-grade adenocarcinoma
|
|
|
• females develop mammary tumors with a median latency of around 290 days
• mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma
• virgin females develop mammary tumors with identical incidence and latency as uniparous females
• tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females
|
|
|
• some mice develop intermediate-grade adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• all females develop mammary tumors with a median latency of 290 days
• mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma
• tumors show benign noninvasive features and consist of large epithelial cells forming solid nests or irregular glands
• tumors only sporadically metastasize to the lung
|
|
|
• some mammary tumors are intermediate-grade adenocarcinoma
|
|
|
• all females develop mammary tumors with a median latency of 290 days
• mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma
• tumors show benign noninvasive features and consist of large epithelial cells forming solid nests or irregular glands
• tumors only sporadically metastasize to the lung
|
|
|
• some mammary tumors are intermediate-grade adenocarcinoma
|
|
|
• all females develop mammary tumors with a median latency of 290 days
• mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma
• tumors show benign noninvasive features and consist of large epithelial cells forming solid nests or irregular glands
• tumors only sporadically metastasize to the lung
|
|
|
• some mammary tumors are intermediate-grade adenocarcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development
• as pregnancy progresses, the mammary gland fills with nonfunctional tissue resulting in complete disruption of the ductal structure at parturition
|
|
|
• mammary glands from females at day 14 of pregnancy show severe ectasia (dilated ducts)
• however, mammary glands from virgin mice show no gross morphological abnormalities
|
|
|
• mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development, with effects becoming more pronounced as pregnancy progresses
|
|
|
• mice develop mammary tumors with a reduced tumor-free survival age of 194 days, with most tumors arising between 150 and 250 days of age
• virgin females develop mammary tumors with identical incidence and latency as uniparous females
• tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females
• mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma and develop in high incidence multifocally in several mammary glands
• most invasive lobular carcinomas are estrogen receptor negative
• females also exhibit solid carcinoma/carcinosarcoma that predominantly show a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns
|
|
|
• mice produce healthy newborns, however all pups fostered by them die before weaning due to starvation
|
|
|
• mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development
• as pregnancy progresses, the mammary gland fills with nonfunctional tissue resulting in complete disruption of the ductal structure at parturition
|
|
|
• mammary glands from females at day 14 of pregnancy show severe ectasia (dilated ducts)
• however, mammary glands from virgin mice show no gross morphological abnormalities
|
|
|
• mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development, with effects becoming more pronounced as pregnancy progresses
|
|
|
• mice develop mammary tumors with a reduced tumor-free survival age of 194 days, with most tumors arising between 150 and 250 days of age
• virgin females develop mammary tumors with identical incidence and latency as uniparous females
• tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females
• mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma and develop in high incidence multifocally in several mammary glands
• most invasive lobular carcinomas are estrogen receptor negative
• females also exhibit solid carcinoma/carcinosarcoma that predominantly show a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns
|
|
|
• mice produce healthy newborns, however all pups fostered by them die before weaning due to starvation
|
|
|
• mice develop mammary tumors with a reduced tumor-free survival age of 194 days, with most tumors arising between 150 and 250 days of age
• virgin females develop mammary tumors with identical incidence and latency as uniparous females
• tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females
• mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma and develop in high incidence multifocally in several mammary glands
• most invasive lobular carcinomas are estrogen receptor negative
• females also exhibit solid carcinoma/carcinosarcoma that predominantly show a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns
|
|
|
• 74% of females that present mammary tumors of about 1 cm show extensive local invasion and metastases to draining and distant lymph nodes
• invasive lobular carcinoma cells are seen in skin, lungs, liver, gastrointestinal tract, pancreas, and spleen or are diffusely disseminated throughout the peritoneal cavity
• several mice develop bone metastases
|
|
|
• mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development
• as pregnancy progresses, the mammary gland fills with nonfunctional tissue resulting in complete disruption of the ductal structure at parturition
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| invasive lobular carcinoma | DOID:3457 | J:171765 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 1 of 7 mice injected with an adenovirus expressing cre recombinase into the bursa develop fluid-filled bursal cysts 6 months after injection
• however, mice injected with an adenovirus expressing cre recombinase into the oviduct exhibit no change in phenotype 3 or 6 months after injection
|
|
|
• 2 of 6 mice injected with an adenovirus expressing cre recombinase into the bursa develop teratoma 3 months after injection
|
|
|
• 1 of 7 mice injected with an adenovirus expressing cre recombinase into the bursa develop fluid-filled bursal cysts 6 months after injection
• however, mice injected with an adenovirus expressing cre recombinase into the oviduct exhibit no change in phenotype 3 or 6 months after injection
|
|
|
• 2 of 6 mice injected with an adenovirus expressing cre recombinase into the bursa develop teratoma 3 months after injection
|
|
|
• 2 of 6 mice injected with an adenovirus expressing cre recombinase into the bursa develop teratoma 3 months after injection
|
|
|
• 1 of 7 mice injected with an adenovirus expressing cre recombinase into the bursa develop fluid-filled bursal cysts 6 months after injection
• however, mice injected with an adenovirus expressing cre recombinase into the oviduct exhibit no change in phenotype 3 or 6 months after injection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• metastasis is much more frequent (6 out of 14 cases) than when Dcc is un-mutated or mutation is heterozygous
• metastases are found in draining lymph nodes and/or lungs
|
|
• high tumor incidence (80%) of mammary tumors regardless of presence or zygosity of Dcc mutation
• single or multiple independent tumors
|
|
• solid tumors with clear demarcations
|
|
• in mammary glands
|
|
• tumor latency of mammary tumors is not modified by the presence or zygosity of Dcc mutation
|
|
• tumor cells in culture cannot be induced to apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• survival is significantly shortened relative to Trp53-sufficient Nf2-deficient mice (almost complete mortality by about 7 months of age)
|
|
• mice develop aggressive osteosarcomas early in life, likely reducing survival time
|
|
• development of malignant peripheral nerve sheath tumours (MPNST) and choroid plexus carcinoma is also seen in some animals, likely reducing survival time
|
|
• mice develop aggressive osteosarcomas early in life, likely reducing survival time
|
|
• development of malignant peripheral nerve sheath tumours (MPNST) and choroid plexus carcinoma is also seen in some animals, likely reducing survival time
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop mammary gland and skin tumors with a latency of 299 days
• mice develop mammary types of carcinoma (38%), biphasic carcinoma that is poorly defined (48%) and biphasic carcinoma that is well defined (14%)
|
|
• mice develop mostly single mammary carcinomas and carcinosarcomas with a median latency of 330 days
• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands
• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology
|
|
• small numbers of skin carcinomas develop with latency of 330 days develop
(J:116152)
• may be classified as pilomatriculomas or squamous cell carcinomas, without metastasis
(J:116152)
• mice develop mammary gland and skin tumors with a latency of 299 days
(J:126551)
|
|
• develop in ~25% of females
|
|
• mice develop mammary gland and skin tumors with a latency of 299 days
• mice develop mammary types of carcinoma (38%), biphasic carcinoma that is poorly defined (48%) and biphasic carcinoma that is well defined (14%)
|
|
• mice develop mostly single mammary carcinomas and carcinosarcomas with a median latency of 330 days
• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands
• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology
|
|
• small numbers of skin carcinomas develop with latency of 330 days develop
(J:116152)
• may be classified as pilomatriculomas or squamous cell carcinomas, without metastasis
(J:116152)
• mice develop mammary gland and skin tumors with a latency of 299 days
(J:126551)
|
|
• mice develop mammary gland and skin tumors with a latency of 299 days
• mice develop mammary types of carcinoma (38%), biphasic carcinoma that is poorly defined (48%) and biphasic carcinoma that is well defined (14%)
|
|
• mice develop mostly single mammary carcinomas and carcinosarcomas with a median latency of 330 days
• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands
• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop tumors with a short median latency period of 360 days
• tumors exhibit expansive growth pattern, a high nuclear grade, and a high mitotic index
|
|
• in 31% of mice
|
|
• mice develop skin carcinomas
|
|
• in 31% of mice
|
|
• mice develop skin carcinomas
|
|
• in 31% of mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop tumors with a short median latency period of 181 days
• tumors exhibit expansive growth pattern, a high nuclear grade, and a high mitotic index
|
|
• in 72% of mice
|
|
• mice develop skin carcinomas
|
|
• in 72% of mice
|
|
• mice develop skin carcinomas
|
|
• in 72% of mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:73028 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants are healthy and fertile and do not develop medulloblastomas and glial malignancies
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop medulloblastomas
|
|
• mutants develop medulloblastomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| medulloblastoma | DOID:0050902 |
OMIM:155255 |
J:61961 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show longer tumor latency periods (330 days) compared to double conditional knockouts (214 days)
• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands
• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology
|
|
• small numbers of skin carcinomas develop with latency of 330 days develop
• may be classified as pilomatriculomas or squamous cell carcinomas, without metastasis
|
|
• mice show longer tumor latency periods (330 days) compared to double conditional knockouts (214 days)
• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands
• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology
|
|
• small numbers of skin carcinomas develop with latency of 330 days develop
• may be classified as pilomatriculomas or squamous cell carcinomas, without metastasis
|
|
• mice show longer tumor latency periods (330 days) compared to double conditional knockouts (214 days)
• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands
• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mammary tumors show less vascularization, especially in periphery compared to double conditional null mice
|
|
• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)
• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands
• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomormphic nuclei; these display both expansive and invasive growth
• massive central necrosis is observed
|
|
• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)
• often show phenotypic change from expansive to invasive growth
• tumors may invade subcutaneous fat or carnous muscle in irregular strands and nest with polymorphic cell with dyskeratosis
|
|
• in females presenting carcinomas ~1 cm in diameter, majority of tumors show extensive local invasion with ~50% demonstrating metastasis to draining and distant lymph nodes
• minority of animals show dissociated or loosely clustered lobulocarcinoma (ILC) cells in lungs, liver, gastrointestinal and urogenital tracts, and pancreas, or diffusely throughout peritoneal cavity
|
|
• mammary tumors show less vascularization, especially in periphery compared to double conditional null mice
|
|
• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)
• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands
• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomormphic nuclei; these display both expansive and invasive growth
• massive central necrosis is observed
|
|
• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)
• often show phenotypic change from expansive to invasive growth
• tumors may invade subcutaneous fat or carnous muscle in irregular strands and nest with polymorphic cell with dyskeratosis
|
|
• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)
• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands
• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomormphic nuclei; these display both expansive and invasive growth
• massive central necrosis is observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mammary tumors show large numbers of uniformly distributed blood vessels
• a 3-fold increase in vasculature is observed compared to mutants homozygous for Cdh1 deletion and heterozygous for Trp53 deletion
|
|
• develop at accelerated rate compared to single conditional Trp53 mutant females
• multiple tumors develop with median latency of 214 days
• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands
• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomorphic nuclei; these display both expansive and invasive growth
|
|
• develop at accelerated rate compared to single conditional Trp53 mutant females
• multiple tumors develop with median latency of 214 days
• often show phenotypic change from expansive to invasive growth
• tumors may invade subcutaneous fat or carnous muscle in irregular strands and nest with polymorphic cell with dyskeratosis
|
|
• in females presenting carcinomas ~1 cm in diameter, majority of tumors show extensive local invasion with ~50% demonstrating metastasis to draining and distant lymph nodes
• minority of animals show dissociated or loosely clustered lobulocarcinoma (ILC) cells in lungs, liver, gastrointestinal and urogenital tracts, and pancreas, or diffusely throughout peritoneal cavity
|
|
• mammary tumors show large numbers of uniformly distributed blood vessels
• a 3-fold increase in vasculature is observed compared to mutants homozygous for Cdh1 deletion and heterozygous for Trp53 deletion
|
|
• develop at accelerated rate compared to single conditional Trp53 mutant females
• multiple tumors develop with median latency of 214 days
• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands
• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomorphic nuclei; these display both expansive and invasive growth
|
|
• develop at accelerated rate compared to single conditional Trp53 mutant females
• multiple tumors develop with median latency of 214 days
• often show phenotypic change from expansive to invasive growth
• tumors may invade subcutaneous fat or carnous muscle in irregular strands and nest with polymorphic cell with dyskeratosis
|
|
• develop at accelerated rate compared to single conditional Trp53 mutant females
• multiple tumors develop with median latency of 214 days
• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands
• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomorphic nuclei; these display both expansive and invasive growth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
• in tamoxifen-treated mice
|
|
|
| ♀ | 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 |
|
• 75% of mice develop lung metastases by 120 days following amputation of limb injected with cre-expressing adenovirus
• in the absence of the Gt(ROSA)26Sortm1(CAG-Mir182)Dgk allele, 43% of mice develop lung metastases
• number of number of metastatic nodules in the lung is increased compared to mice without the Gt(ROSA)26Sortm1(CAG-Mir182)Dgk allel
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 13% of mice develop lung metastases within 6 months following amputation of limb injected with cre-expressing adenovirus
• in the absence of the Mir18tm1.1Dgk allele, 43% of mice develop lung metastases
• number of metastatic nodules and metastatic burden in the lung are decreased compared to mice without the Mir18tm1.1Dgk allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 20% of mice develop lung metastases by 120 days following amputation of limb injected with cre-expressing adenovirus
• in the absence of the Mir18tm1.1Dgk allele, 43% of mice develop lung metastases
• number of metastatic nodules and metastatic burden in the lung are decreased compared to mice without the Mir18tm1.1Dgk allele
|
|
|
| ♀ | 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 |
|
• 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 |
|
• 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 |
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• after RU486 and TPA treatment, 30% of mice develop skin carcinomas compared to 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• survival is shorter than either single conditional mutant; mice can survive up to 32 weeks but most have to be euthanized at 24-26 weeks of age
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• all mice develop pancreatic neoplasms between 16 and 24 weeks
• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas, characterized by the presence of unilocular megacystic lesions with mucoid/watery cyst content, and nodules or peripheral calcification on the cyst wall resembling human mucinous cystic neoplasm
• mucinous cystic neoplasms become malignant pancreatic cancer with nuclear anaplastic features, and show stomach, duodenal or intestinal invasion or liver or lung metastasis, consistent with aggressive pancreatic cystic adenocarcinoma
• 6 week old mice treated with the Wnt inhibitor IWP-2 for 12 weeks show a reduction of or absence of hypertrophic pancreas with cysts
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• tumors exhibit a high incidence of metastasis and invasion
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• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas
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• all mice develop pancreatic neoplasms between 16 and 24 weeks
• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas, characterized by the presence of unilocular megacystic lesions with mucoid/watery cyst content, and nodules or peripheral calcification on the cyst wall resembling human mucinous cystic neoplasm
• mucinous cystic neoplasms become malignant pancreatic cancer with nuclear anaplastic features, and show stomach, duodenal or intestinal invasion or liver or lung metastasis, consistent with aggressive pancreatic cystic adenocarcinoma
• 6 week old mice treated with the Wnt inhibitor IWP-2 for 12 weeks show a reduction of or absence of hypertrophic pancreas with cysts
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• cystic fluid of the pancreata shows the induction of the following cytokines: FasL, soluble tumor necrosis factor receptor 1, IL-1beta, IL-6, macrophage inflammatory protein 1gamma, keratinocyte chemoattractant and monocyte chemoattractant protein 1
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• cystic fluid of the pancreata shows the induction of the following cytokines: FasL, soluble tumor necrosis factor receptor 1, IL-1beta, IL-6, macrophage inflammatory protein 1gamma, keratinocyte chemoattractant and monocyte chemoattractant protein 1
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic mucinous cystadenoma | DOID:7235 | J:234310 | ||
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 04/16/2024 MGI 6.23 |
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