Analysis Tools|
Allele Symbol Allele Name Allele ID |
Trp53+ wild type MGI:1857589 |
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| Summary |
258 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• serum IGF-1 levels are 34% of wild-type
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• at 8, 12 and 24 weeks of age, mammary duct outgrowth is reduced compared to in wild-type mice
• however, proliferation and apoptosis are normal throughout development, pregnancy and involution and treatment with hormones or by cross mice to Tg(TTR-Igf1)1Jxu mice rescues outgrowth
• wild type mammary tissue transplanted into mice exhibits reduced outgrowth
• serial transplants of mammary epithelium exhibit decreased transplant capabilities compared to wild-type epithelium
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• at 8, 12 and 24 weeks of age, mammary duct outgrowth is reduced compared to in wild-type mice
• however, proliferation and apoptosis are normal throughout development, pregnancy and involution and treatment with hormones or by cross mice to Tg(TTR-Igf1)1Jxu mice rescues outgrowth
• wild type mammary tissue transplanted into mice exhibits reduced outgrowth
• serial transplants of mammary epithelium exhibit decreased transplant capabilities compared to wild-type epithelium
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• heterozygous mutants die between 150 to 750 days after birth, however this survival curve is no different from heterozygous Trp53 mice
(J:95318)
• median survival for the combined population of both males and females is 499 days i.e., similar to that of mice heterozygous for both Trp53 tm3.1Glo and Pmltm1Ppp (504 days)
(J:317504)
• median survival is 515 days for male mice and 463 days for female mice
(J:317504)
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• the osteosarcomas and carcinomas of heterozygous mutants metastasized when compared to heterozygous Trp53tm1Tyj mice
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• 31.5% of heterozygous mutants developed lymphomas
(J:95318)
• 52% of mice develop lymphomas (when expressed as a % of tumor type); 13% of mice develop two tumor types, lymphomas and sarcomas
(J:317504)
• 44% of mice exhibit lymphomas when tumor incidence is evaluated per mouse, including those that succumb to EMH, and expressed as a % disease/total number of mice
(J:317504)
• when tumors are segregated by sex, 50% of males and 38% of females exhibit lymphomas (expressed as a % disease/total number of mice)
(J:317504)
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• only ~10% of lymphoid tumors are T-cell lymphomas
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• immunophenotyping of lymphocytes from terminally resected tumors showed that ~90% of lymphoid tumors are B-cell lymphomas
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• 15.5% of heterozygous mutants developed carcinomas, which are rare in homozygotes
(J:95318)
• 4% of mice develop carcinomas (whether expressed as a % of tumor type or as a % disease/total number of mice)
(J:317504)
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• when tumors are segregated by sex, 0% of males and 8% of females exhibit carcinomas (expressed as a % disease/total number of mice)
(J:317504)
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• 53% of heterozygous mutants developed sarcomas
(J:95318)
• 43% of mice develop sarcomas (when expressed as a % of tumor type); 13% of mice develop two tumor types, lymphomas and sarcomas
(J:317504)
• 37% of mice exhibit sarcomas (when expressed as a % disease/total number of mice)
(J:317504)
• when tumors are segregated by sex, 14% of males and 8% of females exhibit soft-tissue sarcomas (expressed as a % disease/total number of mice)
(J:317504)
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• when tumors are segregated by sex, 14% of males and 38% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)
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• higher DNA synthesis in MEFs with cells continuing to synthesize DNA between days 6 and 10 of culture compared to wild-type or heterozygous or homozygous Trp53tm1Tyj MEFs which reached a quiescent state at day 6 and did not reenter the cell cycle
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• irradiated E13.5 heterozygous embryos showed no evidence of apoptosis in the hypothalamus compared to wild-type and heterozygous Trp53tm1Tyj mutants that showed a high number of apoptotic cells
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• MEFs initially did not show any significant differences in growth rate but by day 4, grew more rapidly than wild-type or heterozygous or homozygous null Trp53tm1Tyj MEFs and reached a much higher saturation density
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• only ~10% of lymphoid tumors are T-cell lymphomas
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• mice exhibit pronounced hepatosplenomegaly
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• when segregated by sex, 43% of males and 31% of females exhibit EMH
• 41% mice exhibit extramedullary hematopoiesis (EMH), with no histological evidence of transformation to acute leukemia
• EMH is associated with peripheral blood leukocytosis and macrocytic anemia, indicative of a myeloproliferative/myelodysplastic overlap
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• mice with EMH exhibit macrocytic anemia
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• mice with EMH exhibit peripheral blood leukocytosis
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• only ~10% of lymphoid tumors are T-cell lymphomas
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• mice exhibit pronounced hepatosplenomegaly
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• mice with EMH exhibit peripheral blood leukocytosis
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• mice exhibit pronounced hepatosplenomegaly
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• average body weight is significantly lower than that in C57BL/6 wild-type controls
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• mice exhibit pronounced hepatosplenomegaly
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• when tumors are segregated by sex, 14% of males and 38% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)
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• only ~10% of lymphoid tumors are T-cell lymphomas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Li-Fraumeni syndrome | DOID:3012 |
OMIM:PS151623 |
J:95318 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• between 8 and 15 months of age, mice heterozygous for this mutation develop a variety of solid tumors
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice heterozygous for this mutation develop tumors of various types
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• multinodal lymphoma
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• teratocarcinoma
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Data Sources
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival is 587 days compared with over 770 days for wild-type mice
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• malignant neoplasia in the spleen
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• nonmalignant
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• nonmalignant
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• nonmalignant
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival is 438 days compared with over 770 days for wild-type mice
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• malignant neoplasia in the spleen of most mice
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• nonmalignant in a few mice
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• nonmalignant in a few mice
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• nonmalignant in a few mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 12 of 45 mice treated with 2-AAF develop urinary bladder tumors
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• mean life span is 15.4 months
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• 19% have multiple tumors compared to 44% of Trp53tm3.1Tyj heterozygotes
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• 12 of 45 mice treated with 2-AAF develop urinary bladder tumors
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• 4 of 37 develop low grade carcinomas including 1 with a well differentiated lung carcinoma
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• 12 of 45 mice treated with 2-AAF develop urinary bladder tumors
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• in thymocytes exposed to gamma radiation
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• in response to irradiation
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• a larger fraction of MEFs are in S phase compared to wild-type mice
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• hematopoietic stem and progenitor cells (HSPC) from irradiated mice transplanted into irradiated mice reconstitute the HSPC population exhibit a competitive advantage over HSPC from untreated mice compared with cells from similarly irradiated wild-type mice
• however, no competitive advantage is observed over similarly treated Cdkn2atm2.1Rdp cells in irradiation chimera experiments
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• in response to irradiation
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• in response to irradiation
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• 12 of 45 mice treated with 2-AAF develop urinary bladder tumors
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• in response to irradiation
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Li-Fraumeni syndrome | DOID:3012 |
OMIM:PS151623 |
J:95316 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mortality is not different from wild type controls through 90 days; 3 heterozygotes (with black coat color) died within 1 year suggesting presence of a modifier gene linked to the Aw/a locus with the B6 allele (nonagouti, a) correlating to decreased survival
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| N |
• at 28 days heterozygotes are not different from controls
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• the three mice which died within one year had hypertrophic hearts
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• the three mice which died within one year had hypertrophic hearts
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• foot pads are slightly darker than controls at P28
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• tail skin is slightly darker than controls at P28
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• foot pads are slightly darker than controls at P28
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• tail skin is slightly darker than controls at P28
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• foot pads are slightly darker than controls at P28
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• tail skin is slightly darker than controls at P28
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 42.8% of mice (6 of 14) develop thymic lymphomas after exposure to ionizing radiation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• heterozygous mutants die between 150 to 750 days after birth
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• less than 5% of mice live past two years due to cancerous tumors
(J:135509)
• 28% of mutants die by 17 months of age due to tumors
(J:17728)
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• tumors show loss of heterozygosity for Trp53
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• over 95% of mice have tumors by 2 years of age
(J:135509)
• age of onset 9 months
(J:17728)
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• 2.9% incidence of pancreatic adenocarcinomas
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• 5.9% incidence
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• is observed in 2.6% of mice by 24 months of age
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• 32% incidence
(J:72391)
• 25% of mutants exhibit lymphomas
(J:17728)
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• 15% incidence
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• 35% incidence of carcinomas
(J:72391)
• 2.9% incidence of pancreatic adenocarcinomas
(J:72391)
• 12% of heterozygous mutants developed carcinomas, which are rare in homozygotes
(J:95318)
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• 18% incidence
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• 2.9% incidence
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• 12% incidence
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• 18% incidence of ear squamous cell carcinoma
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• 56% incidence of sarcomas
(J:72391)
• 2.9% incidence of undifferentiated sarcomas
(J:72391)
• 56% of heterozygous mutants developed sarcomas
(J:95318)
• 57% of mutants exhibit sarcomas
(J:17728)
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• 8.8% incidence
(J:72391)
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• 29% incidence
(J:72391)
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• 2.9% incidence
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• 2.9% incidence of pancreatic adenocarcinomas
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• 2.9% incidence
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• 2.9% incidence of small intestinal polyps
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• 2.9% incidence of stomach polyps
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• 12% incidence
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• 29% incidence
(J:72391)
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• Pearl's Prussian blue staining revealed mild iron overload in E8.0 embryos
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Li-Fraumeni syndrome | DOID:3012 |
OMIM:PS151623 |
J:17728 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• radiation-induced apoptosis in the thymus is increased as compared to homozygous Trp53tm1Tyj mice, but is decreased as compared to wild-type
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• radiation-induced apoptosis in the thymus is increased as compared to homozygous Trp53tm1Tyj mice, but is decreased as compared to wild-type
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• radiation-induced apoptosis in the thymus is increased as compared to homozygous Trp53tm1Tyj mice, but is decreased as compared to wild-type
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• radiation-induced apoptosis in the thymus is increased as compared to homozygous Trp53tm1Tyj mice, but is decreased as compared to wild-type
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• average lifespan is 14 months
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• compound mutants which are heterozygous for Trp53tm1Tyj and homozygous wild-type for Trp53bp2 show 7% tumor development over 72 weeks
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• mice show a significant difference in tumor onset compared to Trp53bp2tm1Xlu/+ Trp53tm1Tyj homozygous mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mean life span is 15.8 months
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• compared to Trp53tm1Tyj
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• 5 of 36 develop B cell lymphomas generally arising in the spleen or mesenteric lymph nodes
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• the incidence of carcinomas is increased compared to Trp53tm1Tyj heterozygotes
• 5 of 36 develop squamous cell carcinomas and a single case each of transitional cell renal carcinoma and intestinal carcinoma are seen
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• 2 of 36 develop hepatocellular carcinomas
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• 7 of 36 develop lung adenocarcinomas, several with malignant features commonly seen in human lung adenocarcinoma including nuclear atypia (5 of 7), desmoplasia (4 of 7), and metaplasias (2 of 7)
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• 5 of 36 develop squamous cell carcinomas
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• resistance to gamma-irradiation induced apoptosis is increased compared to Trp53tm1Tyj hterozygotes
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• a larger fraction of MEFs are in S phase compared to Trp53tm1Tyj hterozygotes; however DNA damage-induced G1 arrest is intact
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• 7 of 36 develop lung adenocarcinomas, several with malignant features commonly seen in human lung adenocarcinoma including nuclear atypia (5 of 7), desmoplasia (4 of 7), and metaplasias (2 of 7)
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• 2 of 36 develop hepatocellular carcinomas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Li-Fraumeni syndrome | DOID:3012 |
OMIM:PS151623 |
J:95316 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mean life span is 15.2 months
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• tumors metastisize more frequently than those in Trp53tm1Tyj or Trp53tm3.1Tyj heterozygotes
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• resistance to gamma-irradiation induced apoptosis is increased compared to Trp53tm1Tyj heterozygotes
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• a larger fraction of MEFs are in S phase compared to Trp53tm1Tyj hterozygotes; however DNA damage-induced G1 arrest is intact
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• diffuse osteopetrosis is frequently observed with osteosarcomas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Li-Fraumeni syndrome | DOID:3012 |
OMIM:PS151623 |
J:95316 | |
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the incidence of UV-induced skin tumors including papillomas and squamous cell carcinomas is increased and the latency of skin tumor development is decreased compared to wildtype but not as much as in homozygotes
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• following UV exposure apoptosis in primary MEFs from mutants is decreased compared to wild-type MEFs but increased compared to homozygous mutant MEFs
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• the incidence of UV-induced skin tumors including papillomas and squamous cell carcinomas is increased and the latency of skin tumor development is decreased compared to wildtype but not as much as in homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• more mouse embryonic fibroblasts are in the S-phase compared with wild-type cells
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• irradiated mouse embryonic fibroblasts exhibit a decreased reduction in S-phase populations compared with similarly treated wild-type cells
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• in mouse embryonic fibroblasts
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in 2 mice
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• whether spontaneous or induced, mice develop epithelial, proliferative lesions forming a continuum from nonneoplastic squamous keratosis and acanthosis to squamous cell papillomas, actinic keratosis and keratoacanthoma with increasing degrees of atypia and dysplasia, carcinoma in situ, up to invasive squamous cell carcinoma
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• in 2 mice
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• whether spontaneous or induced, mice develop epithelial, proliferative lesions forming a continuum from nonneoplastic squamous keratosis and acanthosis to squamous cell papillomas, actinic keratosis and keratoacanthoma with increasing degrees of atypia and dysplasia, carcinoma in situ, up to invasive squamous cell carcinoma
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• in 2 mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by day 7 after myocardial infarction, heterozygotes have significantly better survival rate (80% vs. 69% in wild-type) than wild-type
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• heterozygotes exhibit a better survival rate than wild-type and have a lower incidence of left ventricular rupture despite comparable infarct size, heart rate, and mean arterial blood pressure
• exhibit a thicker infarct wall and show fewer numbers of apoptotic cells in the infarct area than in wild-type after myocardial infarction
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• heterozygotes exhibit a better survival rate than wild-type and have a lower incidence of left ventricular rupture despite comparable infarct size, heart rate, and mean arterial blood pressure
• exhibit a thicker infarct wall and show fewer numbers of apoptotic cells in the infarct area than in wild-type after myocardial infarction
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop adenocarcinomas, adenomas, lymphomas, osteosarcoma, and squamous carcinomas
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• including lung adenocarcinomas
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 80% of mice develop life-threatening tumors compared to 45% of wild-type mice over their lifespan
(J:73757)
• mice develop lymphomas, osterosarcomas, soft tissue sarcomas and carcinomas
(J:73757)
• very mild increase in tumor incidence with 2 of 96 heterozygotes developing either embryonal carcinoma or malignant lymphoma (none seen in wild-type)
(J:1999)
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• E12.5 primary telencephalic cultures show a small resistance to AraC induced neuronal cell death relative to wild-type
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• E12.5 primary telencephalic cultures show a small resistance to AraC induced neuronal cell death relative to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• premature death is associated with early onset spontaneous tumor formation
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• mice develop highly metastatic tumors such as osteosarcomas and carcinomas with 17 of 51 mice exhibiting metastasis nodules in the lung, liver or both
• 69% of osteosarcomas metastasize whereas osteosarcomas in mice heterozygous for a Trp53 null allele rarely metastasize
• 40% of adenocarcinomas and squamous cell carcinomas metastasize
• however, fibrosarcomas do not exhibit metastasis
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• mice exhibit an increased rate of tumorigenesis and develop osteosarcomas, fibrosarcomas, angiosarcomas, lyposarcomas, adenocarcinomas, hepatocellular carcinomas, poorly differentiated carcinomas, squamous cell carcinomas, lymphoma and adenoma
• however, tumorigenesis is rarely accompanied by loss of heterozygosity
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• 16% of mice develop lymphomas compared to 25% and 32% of mice heterozygous for one of two Trp53 null allele
|
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• 29% of mice develop carcinomas compared to only 10% of mice heterozygous for a Trp53 null allele
|
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• in 54% of mice
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• old mice treated with Avertin or 5-fluorouracil exhibit increased mortality compared to similarly treated wild-type mice
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• median lifespan is 96 weeks compared to 118 weeks for wild-type mice
|
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• mice exhibit some phenotypes associated with premature ageing
• however, mice do not exhibit liver pathologies, hair graying, alopecia, atrophy of intestinal villi, skin ulcerations, amyloid depositions, brain atrophy, joint disease or cataracts
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• one mouse develops a lung adenoma and another a well-differentiated bronchio-alveolar lung adenocarcinoma
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• following treatment with 5-fluorouracil, mice that survive fail to exhibit a robust recovery as do wild-type mice
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• old mice treated with Avertin or 5-fluorouracil exhibit increased mortality compared to similarly treated wild-type mice
|
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• in old mice
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• one mouse develops a lung adenoma and another a well-differentiated bronchio-alveolar lung adenocarcinoma
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• mice do not develop any life-threatening tumors over the course of their lifespan compared to 45% of wild-type mice
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• by 18 months of age, mice exhibit lordokyphosis
|
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• at 24 months of age
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• at 24 months of age, mean quadriceps mass is 2.5-fold lower than in wild-type mice
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• in older mice
|
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age
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• by 18 months of age
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• mouse embryonic fibroblasts are 2 to 4 fold more resistant to transformation than wild-type cells
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age
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• at 24 months of age, mice display reduced adipose deposition compared to wild-type mice
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• at 24 months of age, mice display reduced adipose deposition compared to wild-type mice
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• by 22 to 24 months of age, no hair growth is observed
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• at 24 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased numbers of apoptotic cells induced by UV irradiation are observed in MEFs compared to wild-type
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival is 465 days compared with 589 days for null heterozygotes
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• mice exhibit increased tumor incidence compared with null heterozygotes
• 17% of mice develop benign tumors (skin hamartoma, colon, hamartoma, lung adenoma, colon adenoma, and hibernoma)
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• in the colon of some mice
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• luteoma of pregnancy in some mice
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• in some mice
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• in some mice
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• in some mice
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• 4% of mice exhibit DLBCL and sarcoma
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• all mice exhibit metastasized osteosarcomas
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• prior to and after tumor development, mice exhibit lymphocyte aggregates in the liver and lungs unlike wild-type mice
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• prominent in the colon prior to and after tumor development
|
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• some mice exhibit generalized inflammation
• 60% of mice develop inflammation
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• lobulitis, hepatitis, or cirrhosis of the liver in 27% of mice
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• lobulitis, hepatitis, or cirrhosis of the liver in 27% of mice
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• prior to and after tumor development
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• lobulitis, hepatitis, or cirrhosis of the liver in 27% of mice
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• 27% of mice exhibit vasculitis affecting the skin, heart, aorta, kidney, or seminal vesicles vessels unlike wild-type mice
|
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• prior to and after tumor development
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• prior to and after tumor development, mice exhibit lymphocyte aggregates in the liver and lungs unlike wild-type mice
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• luteoma of pregnancy in some mice
|
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• all mice exhibit metastasized osteosarcomas
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• in the colon of some mice
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• in some mice
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• luteoma of pregnancy in some mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show increased susceptibility to diethylnitrosamine (DEN)-induced liver carcinogenesis, with mice showing an increase in the number and size of tumors on the surface of the liver
• however, incidence of carcinomas in the liver is not different from wild-type
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• mice show increased susceptibility to diethylnitrosamine (DEN)-induced liver carcinogenesis, with mice showing an increase in the number and size of tumors on the surface of the liver
• however, incidence of carcinomas in the liver is not different from wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mouse embryonic fibroblasts exhibit a normal G2/M checkpoint after irradiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following irradiation, mouse embryonic fibroblasts and thymocytes exhibit an impaired G2/M checkpoint compared with wild-type cells
|
|
• interchromosomal translocation are observed thymocytes unlike in wild-type cells
|
|
• following irradiation, thymocytes exhibit an impaired G2/M checkpoint compared with wild-type cells
|
|
• following irradiation, thymocytes exhibit an impaired G2/M checkpoint compared with wild-type cells
|
|
• following irradiation, thymocytes exhibit an impaired G2/M checkpoint compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• heterozygous embryos are completely resorbed by E10.5
|
|
|
| ♀ | 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 |
| N |
• hematopoietic stem and progenitor cells of irradiated mice treated with tamoxifen do not exhibit a selective advantage over cells not expressing the modified cDNA
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• loss of heterozygosity of Trp53 in the neuroendocrine tumors
|
|
• develop pituitary gland and pineal gland tumors
• pinealoblastomas locally invade the brain
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop pancreatic cancer
|
|
• all pancreata of 7-month old mice are replaced by aggressive pancreatic ductal adenocarcinoma with lung and liver metastasis
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring pancreatic adenocarcinoma
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
|
|
• average survival is 5.2 +/- 1.2 months
|
|
• mice develop pancreatic cancer
|
|
• all pancreata of 7-month old mice are replaced by aggressive pancreatic ductal adenocarcinoma with lung and liver metastasis
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring pancreatic adenocarcinoma
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
|
|
• 100% of 3-month old mice exhibit abundant acinar-ductal metaplasia and low- and high-grade pancreatic intraepithelial neoplasia (PanIN) lesions
• circulating pancreatic neoplastic cells are increased in the blood of mice harboring PanI
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:289183 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• 73.3% of 3-month old and 75% of 12-month old mice show normal pancreas
• although 26.7% of 3-month old and 25% of 12-month old mice show rare acinar-ductal metaplasia and low-grade pancreatic intraepithelial neoplasia (PanIN1) lesions, these lesions express TRIM29 due to incomplete recombination of the floxed allele
|
| N |
• all mice are alive at 12 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average survival is 8.5 +/- 2.3 months
|
|
• initiation and progression of acinar-ductal metaplasia and pancreatic intraepithelial neoplasia (PanIN) lesions are slower than in Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53+ Gt(ROSA)26Sortm1(EYFP)Cos/Gt(ROSA)26Sor+ (KPCY) mice
• mice show lower pancreatic ductal adenocarcinoma and metastasis incidence than in KPCY mice
|
|
• mice show lower lung and liver metastasis from pancreatic ductal adenocarcinoma than in KPCY mice
|
|
• initiation and progression of acinar-ductal metaplasia and pancreatic intraepithelial neoplasia (PanIN) lesions are slower than in Krastm4Tyj/Kras+ Trp53tm1Brn/Trp53+ Gt(ROSA)26Sortm1(EYFP)Cos/Gt(ROSA)26Sor+ (KPCY) mice
• mice show lower pancreatic ductal adenocarcinoma and metastasis incidence than in KPCY mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants develop pancreatic tumors with an average latency of 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 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 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 |
|
• mice exhibit an intermediate footpad pigmentation phenotype and reduced Kitl mRNA levels in the footpad epidermis at P30, indicating partial amelioration of the dark skin observed in mice that are only heterozygous for Rps6tm1Gtho and hemizygous for Tg(KRT5-cre)5132Jlj
|
|
• mice exhibit an intermediate footpad pigmentation phenotype and reduced Kitl mRNA levels in the footpad epidermis at P30, indicating partial amelioration of the dark skin observed in mice that are only heterozygous for Rps6tm1Gtho and hemizygous for Tg(KRT5-cre)5132Jlj
|
|
• mice exhibit an intermediate footpad pigmentation phenotype and reduced Kitl mRNA levels in the footpad epidermis at P30, indicating partial amelioration of the dark skin observed in mice that are only heterozygous for Rps6tm1Gtho and hemizygous for Tg(KRT5-cre)5132Jlj
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a similar overall pancreatic tumor burden as KPCT (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor+) mice
• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice
• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells
• cancer cells exhibit a higher mitotic index than KPCT mice
|
|
• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice
|
|
• mice exhibit a shorter survival than KPCT mice
|
|
• mice exhibit a similar overall pancreatic tumor burden as KPCT (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor+) mice
• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice
• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells
• cancer cells exhibit a higher mitotic index than KPCT mice
|
|
• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• pancreas contains PanINs and adenocarcinoma
|
|
• most mice develop metastases which are numerous and widespread in many different sites, including the lymph nodes, diaphragm, lungs, and liver
• all mice exhibit peritoneal disseminated tumor cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 100% of mice develop medulloblastoma beginning at 10 weeks
|
|
• 100% of mice develop medulloblastoma beginning at 10 weeks
|
|
|
| ♀ | 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 |
|
• 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 |
|
• 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 |
|
• 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 |
|
• 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 |
|
• tumors exhibit a loss of heterozygosity at the Trp53 gene
|
|
• 72% of mice develop medulloblastoma beginning at 21 weeks
|
|
• 72% of mice develop medulloblastoma beginning at 21 weeks
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| medulloblastoma | DOID:0050902 |
OMIM:155255 |
J:144617 | |
|
|
| ♀ | 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 |
|
|
• mice show widespread peritoneal metastases, including omentum and diaphragm
• the overall metastatic tumor burden in fallopian tube-removed mice is less extensive than that of intact mice
|
|
|
• mice develop massive high-grade serous carcinomas that always arise from the fallopian tube
• however when fallopian tubes are removed, mice develop high-grade serous carcinomas originating from the ovary, indicating that the ovary can be a source of carcinomas but is less dominant in tumorigenesis than the fallopian tube
|
|
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
|
|
• premature death starting around 6 months of age with all mice dying by around 8 months of age
• fallopian tube-removed mice die at around 8-14 months of age after inducing ascites
|
|
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
|
|
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:222579 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 70% of mice develop granulosa-cell tumors in the ovary
|
|
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
|
|
• serous carcinoma spreads throughout the peritoneal cavity, to the omentum and across the peritoneal membrane, including the mesentery and diaphragm
|
|
|
• median survival is 11.2 months of age, with mice dying between 7.6 and 15.3 months of age
|
|
|
• 70% of mice develop granulosa-cell tumors in the ovary
|
|
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
|
|
• 70% of mice develop granulosa-cell tumors in the ovary
|
|
|
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| ovarian cancer | DOID:2394 |
OMIM:167000 OMIM:607893 |
J:222579 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in mice lacking the BRF1 knock-in
|
|
• as in mice lacking the BRF1 knock-in
|
|
• tRNA levels are increased in the pancreas
|
|
• as in mice lacking the BRF1 knock-in
|
|
• tRNA levels are increased in the pancreas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
• at 8 weeks, not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
• increased tumor weight compared to in mice homozygous for a conditional allele
|
|
• compared to in mice homozygous for a conditional allele
|
|
• at 8 weeks, not as severe as in mice wild-type for Cd9 or homozygous for a conditional allele
• increased tumor weight compared to in mice homozygous for a conditional allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die by 30 weeks of age
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
• at 8 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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 |
| 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 |
|
• tamoxifen treated mice exhibit shortened survival
|
|
• tamoxifen treated mice develop large papillary thyroid carcinoma that exhibit features associated with aggressive behavior including solid growth, tall cell morphology, focal necrosis, and hobnail features
• about 50% of mice with papillary thyroid carcinoma acquire poorly differentiated thyroid carcinoma or undifferentiated anaplastic thyroid carcinoma
|
|
• tamoxifen treated mice develop large papillary thyroid carcinoma that exhibit features associated with aggressive behavior including solid growth, tall cell morphology, focal necrosis, and hobnail features
• about 50% of mice with papillary thyroid carcinoma acquire poorly differentiated thyroid carcinoma or undifferentiated anaplastic thyroid carcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean survival is 52 weeks of age
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age
• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
|
• tumors are highly metastatic, with tumors showing invasion into adjacent organs such as the diaphragm, bowel, pancreas and stomach or distant metastasis to the lymph nodes, spleen, lungs, or peritoneal cavity
|
|
• intrahepatic cholangiocarcinoma is associated with biliary hamartomas
|
|
• hepatic lesions frequently show hemorrhage into the peritoneal cavity and exhibit evidence of tumor necrosis
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age
• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
|
• mutants develop intrahepatic cholangiocarcinoma as early as 32 weeks of age
• intrahepatic cholangiocarcinoma recapitulates the histologic and molecular features of multistage progression of human intrahepatic cholangiocarcinoma
• intrahepatic cholangiocarcinoma is associated with intraductal papillary neoplasms of the bile ducts and Von Meyenburg complexes, or biliary hamartomas
• intrahepatic cholangiocarcinoma is characterized by elevated levels of autophagy
• different grades of differentiation are seen in the same tumor
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| intrahepatic cholangiocarcinoma | DOID:4928 | J:184949 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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 |
|
• 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 |
|
• 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 |
|
• mice develop mammary tumor faster than Trp53tm1Brn/Trp53+ Tg(KRT14-cre)1Amc mice
|
|
|
| ♀ | 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 |
|
• 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 |
|
• a decrease in granulocyte/macrophage colony-forming units in bone marrow
• by flow cytometry, there is a reduction in granulocyte-monocyte progenitors in the bone marrow
|
|
• as measured by erythroid colony-forming units in bone marrow
|
|
• a reduced number of circulating red blood cells
|
|
• in bone marrow and spleen
|
|
• by flow cytometry, there is a reduction in megakaryocytic-erythroid progenitors in the bone marrow
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• foliation structure is improved compared to mutants wild-type for Trp53
|
|
• a marginal increase in granule cell numbers is seen compared to mutants wild-type for Trp53
|
|
• performance on the balance beam test is improved compared to mutants wild-type for Trp53 but is impaired compared to controls and mutants that are homozygous null for Trp53
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 11 of 36 mice develop mammary tumors consisting of solid carcinoma, carcinosarcoma, adenosquamous carcinoma, and osteosarcoma
• incidence of mammary tumors is increased while latency to development of tumors is decreased compared with Trp53tm1Brd heterozygotes
|
|
• in the mammary tissue of some mice
|
|
• in the mammary tissue of one mouse
|
|
• 11 of 36 mice develop mammary tumors consisting of solid carcinoma, carcinosarcoma, adenosquamous carcinoma, and osteosarcoma
• incidence of mammary tumors is increased while latency to development of tumors is decreased compared with Trp53tm1Brd heterozygotes
|
|
• in the mammary tissue of one mouse
|
|
• 11 of 36 mice develop mammary tumors consisting of solid carcinoma, carcinosarcoma, adenosquamous carcinoma, and osteosarcoma
• incidence of mammary tumors is increased while latency to development of tumors is decreased compared with Trp53tm1Brd heterozygotes
|
|
|
| ♀ | 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 |
|
• 4 of 12 mice die prematurely due to malignant peripheral nerve sheath tumors, 3 of which are 5 months old
|
|
• in 4 of 12 mice
|
|
• in 4 of 12 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median age of death is 4.5 months
|
|
• 23% of mice develop osseous metaplasia
|
|
• one mouse developed lymphosarcoma
|
|
• in 8% of mice with metastasis to the liver
|
|
• 85% of mice develop peripheral nerve tumors
|
|
• 8% of mice develop neurofibroma
|
|
• 77% of mice develop peripheral nerve tumors from peripheral nerves of the limbs and from the dorsal root ganglia
|
|
• 11% of mice develop schwannoma
|
|
• 35% of mice exhibit odontoblastic hyperplasia
|
|
• 15% of mice develop osteogenic hyperplasia
|
|
• 81% of mice exhibit Schwann cell hyperplasia with increased incidence of diffuse Schwann cell hyperplasia in major peripheral nerve trunks
|
|
• 85% of mice develop peripheral nerve tumors
|
|
• 8% of mice develop neurofibroma
|
|
• 77% of mice develop peripheral nerve tumors from peripheral nerves of the limbs and from the dorsal root ganglia
|
|
• 11% of mice develop schwannoma
|
|
• 73% of mice exhibit renal tubular cell hyperplasia
|
|
• 35% of mice exhibit odontoblastic hyperplasia
|
|
• 35% of mice exhibit odontoblastic hyperplasia
|
|
• in 8% of mice with metastasis to the liver
|
|
• 81% of mice exhibit Schwann cell hyperplasia with increased incidence of diffuse Schwann cell hyperplasia in major peripheral nerve trunks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a decrease in survival rate when the Nf2 and Trp53 alleles are carried in cis as opposed to trans, but live longer than conditional mutants carrying Tg(P0-Cre)2Gth
|
|
• between 3.5 and 13.5 months,19% of mice develop malignant peripheral nerve sheath tumors when the Nf2 and Trp53 alleles are carried in cis
• however, no tumors form in mice when the Nf2 and Trp53 alleles are carried in trans
|
|
• when the Nf2 and Trp53 alleles are carried in trans mice develop osteogenic tumors not restricted to neural crest-derived bone
|
|
• 81% of mice develop osteogenic (osteomas and osteosarcomas) tumors when the Nf2 and Trp53 alleles are carried in cis
|
|
• 81% of mice develop osteogenic (osteomas and osteosarcomas) tumors when the Nf2 and Trp53 alleles are carried in cis
|
|
• when the Nf2 and Trp53 alleles are carried in trans mice develop osteogenic tumors not restricted to neural crest-derived bone
|
|
• 81% of mice develop osteogenic (osteomas and osteosarcomas) tumors when the Nf2 and Trp53 alleles are carried in cis
|
|
• 81% of mice develop osteogenic (osteomas and osteosarcomas) tumors when the Nf2 and Trp53 alleles are carried in cis
|
|
• between 3.5 and 13.5 months,19% of mice develop malignant peripheral nerve sheath tumors when the Nf2 and Trp53 alleles are carried in cis
• however, no tumors form in mice when the Nf2 and Trp53 alleles are carried in trans
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pancreatic insufficiency is occasionally observed in mutants
|
|
• pancreatic insufficiency is occasionally observed in mutants
|
|
• premature death before 600 days of age due to lymphoid malignancies and sarcomas
|
|
• mutants develop lymphoid malignancies
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 18% of assessable tumor cases develop an acinar-cell carcinoma component of pancreatic tumors
|
|
• high penetrance (29 of 30 mutants) of pancreatic ductal adenocarcinomas
|
|
• average survival time is 84 days, with a range of 48-110 days
|
|
• about 18% of assessable tumor cases develop an acinar-cell carcinoma component of pancreatic tumors
|
|
• high penetrance (29 of 30 mutants) of pancreatic ductal adenocarcinomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:166678 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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 |
|
• 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 |
|
• 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 |
|
• about 80% develop acinar adenocarcenomas
|
|
• about 80% develop acinar adenocarcenomas
|
|
• about 80% develop acinar adenocarcenomas
|
|
|
| ♀ | 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 |
|
• 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 |
|
• 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 |
|
• 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 |
|
• 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 |
|
|
• 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 |
|
• skin tumors develop between 500 and 600 days
• UVB exposure results in 2.4+/-0.6 tumors at day 100 compared to 6.5+/-1.4 in Trp53tm3Tyj Tg(KRT14-cre)8Brn heterozygotes and 0.6+/-0.2 in wild-type mice
• whether spontaneous or induced, mice develop epithelial, proliferative lesions forming a continuum from nonneoplastic squamous keratosis and acanthosis to squamous cell papillomas, actinic keratosis and keratoacanthoma with increasing degrees of atypia and dysplasia, carcinoma in situ, up to invasive squamous cell carcinoma
|
|
• fewer CASP3+ cells area found following UVB treatment when compared to wild-type mice
• the reduction in apoptotic cells is slightly greater in homozygotes than in heterozygotes
|
|
• skin tumors develop between 500 and 600 days
• UVB exposure results in 2.4+/-0.6 tumors at day 100 compared to 6.5+/-1.4 in Trp53tm3Tyj Tg(KRT14-cre)8Brn heterozygotes and 0.6+/-0.2 in wild-type mice
• whether spontaneous or induced, mice develop epithelial, proliferative lesions forming a continuum from nonneoplastic squamous keratosis and acanthosis to squamous cell papillomas, actinic keratosis and keratoacanthoma with increasing degrees of atypia and dysplasia, carcinoma in situ, up to invasive squamous cell carcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a decrease in median survival time which is approximately 4.5 months of age
|
|
• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs with only 2 mice showing liver metastasis
|
|
• both low and high grade PanIN lesions are seen at 2-3 months of age, but by 6 months, invasive carcinoma is present
|
|
• mice develop invasive pancreatic ductal adenocarcinoma
• however, mice show negligible metastasis to distant organs with only 2 mice showing liver metastasis
|
|
• both low and high grade PanIN lesions are seen at 2-3 months of age, but by 6 months, invasive carcinoma is present
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:248550 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity
|
|
• exaggerated startle response
|
|
• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas
• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1tm1Par and Trp53tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes
|
|
• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas
• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1tm1Par and Trp53tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:134611 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants survive up to 8 weeks beyond initial appearance of symptoms
|
|
• complete penetrance of malignant astrocytomas
• gliomas from asymptomatic mutants are primarily classified as grade 2 astocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci
|
|
• complete penetrance of malignant astrocytomas
• gliomas from asymptomatic mutants are primarily classified as grade 2 astocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:134611 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by 6 months of age
|
|
• in 13% of mice
|
|
• in 13% of mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by 32 weeks
|
|
• tumors exhibit a loss of heterozygosity at the Trp53 gene
|
|
• 75% of mice develop medulloblastoma beginning at 23 weeks
|
|
• 75% of mice develop medulloblastoma beginning at 23 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 308 days compared with 380 days in Trp53tm3Tyj Waptm1(cre)Arge double heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared with Brca1tm2.1Cxd/Brca1tm2.1Cxd Trp53tm3Tyj/Trp53tm3Tyj Waptm1(cre)Arge/Waptm1(cre)Arge
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 308 days compared with 380 days in Trp53tm3Tyj Waptm1(cre)Arge double heterozygotes
• however, latency is similar to in Brca1tm2.1Cxd/Brca1tm2.1Cxd Trp53tm3Tyj/Trp53+ Waptm1(cre)Arge/Wap+
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity
|
|
• exaggerated startle response
|
|
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci
|
|
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants survive up to 8 weeks beyond initial appearance of symptoms
|
|
• exaggerated startle response
|
|
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci
|
|
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:134611 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some (2/59) develop salivary gland malignant myoepithelial tumors
|
|
• mice develop mammary gland tumors with higher frequency (64%; 25/39 animals) and shorter latency of 6-46 weeks (all but one tumor had developed by 31 weeks) relative to control mice; 6/39 mice had multiple tumors in the same and in adjacent glands
• tumors develop in the inguinal and thoracic glands with equal frequency, and on both sides of the body
• majority of tumors (30/33) show marked nuclear pleomorphism; central necrosis is seen in about 67% of tumors (23/32)
• most (29/33) neoplasms show mixed pushing and infiltrative borders, while only 4/33 showed a prominent inflammatory infiltrate
• most (29/33) tumors show homologous metaplastic elements in form of squamous or spindly differentiation
|
|
• high grade ductal carcinoma in situ (DCIS) is observed admixed with, or adjacent to, the invasive tumor in some cases, and occasionally columnar cell lesions with cytological atypia are seen with those tumors; columnar cell changes are found in adjacent tissue in a few tumors
|
|
• some (2/59) develop salivary gland malignant myoepithelial tumors
|
|
|
• only 2/33 tumors show beta-catenin upregulation that was restricted to areas of squamous differentiation and basaloid cells
|
|
• mice develop mammary gland tumors with higher frequency (64%; 25/39 animals) and shorter latency of 6-46 weeks (all but one tumor had developed by 31 weeks) relative to control mice; 6/39 mice had multiple tumors in the same and in adjacent glands
• tumors develop in the inguinal and thoracic glands with equal frequency, and on both sides of the body
• majority of tumors (30/33) show marked nuclear pleomorphism; central necrosis is seen in about 67% of tumors (23/32)
• most (29/33) neoplasms show mixed pushing and infiltrative borders, while only 4/33 showed a prominent inflammatory infiltrate
• most (29/33) tumors show homologous metaplastic elements in form of squamous or spindly differentiation
|
|
• high grade ductal carcinoma in situ (DCIS) is observed admixed with, or adjacent to, the invasive tumor in some cases, and occasionally columnar cell lesions with cytological atypia are seen with those tumors; columnar cell changes are found in adjacent tissue in a few tumors
|
|
|
• only 2/33 tumors show beta-catenin upregulation that was restricted to areas of squamous differentiation and basaloid cells
|
|
• mice develop mammary gland tumors with higher frequency (64%; 25/39 animals) and shorter latency of 6-46 weeks (all but one tumor had developed by 31 weeks) relative to control mice; 6/39 mice had multiple tumors in the same and in adjacent glands
• tumors develop in the inguinal and thoracic glands with equal frequency, and on both sides of the body
• majority of tumors (30/33) show marked nuclear pleomorphism; central necrosis is seen in about 67% of tumors (23/32)
• most (29/33) neoplasms show mixed pushing and infiltrative borders, while only 4/33 showed a prominent inflammatory infiltrate
• most (29/33) tumors show homologous metaplastic elements in form of squamous or spindly differentiation
|
|
• high grade ductal carcinoma in situ (DCIS) is observed admixed with, or adjacent to, the invasive tumor in some cases, and occasionally columnar cell lesions with cytological atypia are seen with those tumors; columnar cell changes are found in adjacent tissue in a few tumors
|
|
• some (2/59) develop salivary gland malignant myoepithelial tumors
|
|
• some (2/59) develop salivary gland malignant myoepithelial tumors
|
|
• some (2/59) develop salivary gland malignant myoepithelial tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% mortality by 6 months of age
• 100% mortality by 1 year of age
|
|
• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions
|
|
• metastases develop affecting liver, diaphragm, lungs, lymph nodes, and spleen
|
|
• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:119988 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between 8 and 18 weeks after doxycycline (dox) treatment to induce Kras2 expression due to pancreatic ductal adenocarinoma
|
|
• mice develop invasive adenocarcinoma between 8 and 18 weeks after dox treatment, with some cases showing hemorrhagic ascites, with admixed poorly differentiated and well-differentiated areas and duodenal invasion
• mice in which dox is removed recover their health and show pancreatic tumor regression resulting in a small pancreatic remnant
|
|
• adult mice treated with dox 72 hours prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis develop PanINs, dilated ducts with the presence of intracellular mucins, and extensive fibroinflammatory stroma
|
|
• adult mice treated with dox for 5 weeks prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis exhibit a small, translucent remnant of pancreatic tissue, without fibrosis or PanIN lesions
• when dox is removed after pancreatitis induction, mice show show normal acini interspersed with dilated ducts and acinar-ductal metaplasia, fibrosis and occasional lipomatosis, but with minimal inflammatory infiltrate, and reduced proliferation
|
|
• mice develop invasive adenocarcinoma between 8 and 18 weeks after dox treatment, with some cases showing hemorrhagic ascites, with admixed poorly differentiated and well-differentiated areas and duodenal invasion
• mice in which dox is removed recover their health and show pancreatic tumor regression resulting in a small pancreatic remnant
|
|
• adult mice treated with dox 72 hours prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis develop PanINs, dilated ducts with the presence of intracellular mucins, and extensive fibroinflammatory stroma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:184378 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show an extended median survival of 274 days compared to compound heterozygous Mdm4tm2Glo/Mdm4tm2.1Glo conditional mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E10 - 11.5 the number of apoptotic cells in the brain is increased
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
(J:103407)
• following cre-adenovirus treatment, tumors occupy 27% of lung space
(J:103407)
• mice treated with intratracheal delivery of cre-expressing adenovirus develop lung cancer
(J:191425)
• mice infected with higher doses of cre expressing adenovirus present with clinical signs of lung cancer by 15 weeks of treatment while lower dosed animals show signs of disease around 37 weeks
(J:191425)
• a subset of tumors from mice treated with intratracheal delivery of cre-expressing adenovirus show loss of heterozygosity of Trp53
(J:191425)
• treatment of mice treated with intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus almost completely abrogates tumor formation
(J:191425)
• treatment of mice that have already formed lung tumors following intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus prevents further progression of tumors
(J:191425)
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus show evidence that high-grade adenocarcinomas acquire metastatic characteristics of non-small cell lung cancer
|
|
• tumors of mice treated with intratracheal delivery of cre-expressing adenovirus are adenocarcinomas and some evidence that high-grade adenocarcinomas acquire metastatic characteristics
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit large lungs filled with tumors and inflammation
• the inflammation that develops in the lungs of mice treated with intratracheal delivery of cre-expressing adenovirus occurs after initial nodules develop
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus develop a hunched posture in the most severe cases
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit a decline in weight
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit large lungs filled with tumors and inflammation
• the inflammation that develops in the lungs of mice treated with intratracheal delivery of cre-expressing adenovirus occurs after initial nodules develop
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are similar to those found in Krastm4Tyj Trp53tm1Brn heterozygotes
(J:103407)
• following cre-adenovirus treatment, tumors occupy 27% of lung space
(J:103407)
• mice treated with intratracheal delivery of cre-expressing adenovirus develop lung cancer
(J:191425)
• mice infected with higher doses of cre expressing adenovirus present with clinical signs of lung cancer by 15 weeks of treatment while lower dosed animals show signs of disease around 37 weeks
(J:191425)
• a subset of tumors from mice treated with intratracheal delivery of cre-expressing adenovirus show loss of heterozygosity of Trp53
(J:191425)
• treatment of mice treated with intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus almost completely abrogates tumor formation
(J:191425)
• treatment of mice that have already formed lung tumors following intratracheal delivery of cre-expressing adenovirus with an miR-34 expressing lentilvirus prevents further progression of tumors
(J:191425)
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus show evidence that high-grade adenocarcinomas acquire metastatic characteristics of non-small cell lung cancer
|
|
• tumors of mice treated with intratracheal delivery of cre-expressing adenovirus are adenocarcinomas and some evidence that high-grade adenocarcinomas acquire metastatic characteristics
|
|
• mice treated with intratracheal delivery of cre-expressing adenovirus exhibit labored breathing
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:191425 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are shifted towards more lower grade tumor types
• following cre-adenovirus treatment, tumors occupy 36% of lung space
|
|
• following cre-adenovirus treatment, all mice develop primary lung tumors that are shifted towards more lower grade tumor types
• following cre-adenovirus treatment, tumors occupy 36% of lung space
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice develop pancreatic ductal adenocarcinoma (PDAC)
|
|
• mice develop pancreatic ductal adenocarcinoma (PDAC)
|
|
• GFP+ PDAC cells form tumors form more metastases than GFP- PDAC cells when transplanted into recipient mice
• the highly metastatic PDAC subpopulation is enriched for hypoxia-induced genes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:245611 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 9 of 12 mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
|
• median lifespan is approximately 120 days with all mice dying around 260 days, which is extended survival compared to conditional mice expressing the Krastm4Tyj allele
|
|
• 9 of 12 mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:276349 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• extended survival compared to control mice with normal Brf1
|
|
• at a reduced rate and with extended survival compared to control mice with normal Brf1
• however, tumors that do form lack recombined Brf1
|
|
• at a reduced rate and with extended survival compared to control mice with normal Brf1
• however, tumors that do form lack recombined Brf1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no viable adults are found and no postnatal lethality is detected suggesting mice die in the prenatal period
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 83% of hearts exhibit outflow tract defects such as persistent truncus arteriosus and double outlet right ventricle
|
|
• in 33% of E12.5 embryos
|
|
• atrioventricular cushions fail to undergo remodeling
|
|
• increase in apoptosis in the retina, neural crest cells, the thymus, neuroepithelium, and otic vesicles
|
|
• decrease in proliferation in the retina, neural crest cells, the thymus, neuroepithelium, and otic vesicles
|
|
• E13.5 or older embryos commonly exhibit craniofacial defects, including square-shaped faces, short lower jaws, cleft lip and cleft palate
|
|
• short lower jaws 74% of embryos
|
|
• square-shaped faces in some E13.5 or older embryos
|
|
• in some E13.5 or older embryos
|
|
• in some E13.5 or older embryos
|
|
• protruding tongue due to short jaw
|
|
• 41% of embryos exhibit defects in external ear formation
|
|
• in some E13.5 or older embryos
|
|
• protruding tongue due to short jaw
|
|
• neural tube closure defects
|
|
• square-shaped faces in some E13.5 or older embryos
|
|
• in some E13.5 or older embryos
|
|
• in some E13.5 or older embryos
|
|
• protruding tongue due to short jaw
|
|
• 41% of embryos exhibit defects in external ear formation
|
|
• 41% of embryos exhibit defects in external ear formation
|
|
• 71% of embryos exhibit a spectrum of inner ear defects, ranging from mild (either truncated posterior semi-circular canal or fused to the common crus) to highly abnormal (extreme inner ear bone malformation)
|
|
• embryonic lethality between E13.5 and E15.5
|
|
• neural tube closure defects
|
|
• 63 % of E13.5 or older embryos exhibit exencephaly
|
|
• kidneys show branching defects
|
|
• short lower jaws 74% of embryos
|
|
• reduction in bone density in the cranium, nasal cavity, ulna, humerus, mandible and femur
|
|
• delay in bone formation in embryos
|
|
• in 59% of embryos
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CHARGE syndrome | DOID:0050834 |
OMIM:214800 |
J:217080 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• seen in older males
|
|
• tumor formation is more prevalent and starts earlier in males compared to females
|
|
• preneoplastic nodules are first detected at about 160 days of age in males
• liver nodules in quadruple transgenic mice are larger and more numerous compared to triple transgenic mice that are wild-type at the Trp53 locus
|
|
• seen in older males
|
|
• tumor formation is more prevalent and starts earlier in males compared to females
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 24 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
• average survival time is 168 days, with a range of 60-254 days
|
|
• 24 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• survival is similar to mutant mice wild-type for Zdhhc20
|
|
• liver metastases are found in 40% of mice compared to 93% of mutant mice wild-type for Zdhhc20
• a similar trend is seen for lung metastases
• both total liver lesion area and number are profoundly reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
|
• median lifespan is approximately 70 days, with all mice dying around 120 days
|
|
• all mice develop pancreatic tumors; all cancers are invasive pancreatic ductal adenocarcinoma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:276349 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 2 mice
|
|
• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors
• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes
• mice exhibit the full spectrum of preinvasive lesions
• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features
|
|
• in young mice
|
|
• in one mouse
|
|
• some mice exhibit esophageal papillomas and hyperplasias or papillomatosis of the biliary tree unlike control mice
|
|
• in some mice
|
|
• hemorrhagic
|
|
• in tumor cells
|
|
• in some mice
|
|
• mice frequently exhibit small bowel obstructions unlike control mice
|
|
• in 2 mice
|
|
• all but one mouse, develop large, firm, fibrotic head of the pancreas tumors
• metastatic foci spread to the surface of the liver, lungs, diaphragm, and adrenals with occasional metastasis to the peripancreatic, mesenteric, and retroperitoneal lymph nodes
• mice exhibit the full spectrum of preinvasive lesions
• some tumors are minor, poorly differentiated, or undifferentiated with anaplastic or sarcomatoid features
|
|
• in young mice
|
|
• in 2 mice
|
|
• in 2 mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic ductal adenocarcinoma | DOID:3498 | J:98936 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• erythropoietic recovery and spleen size after induction of acute hemolytic stress with 25 mg/kg phenylhydrazine
• no mortality after induction of acute hemolytic stress with high-dose (35 mg/kg) phenylhydrazine
|
| N |
• spleen size after induction of acute hemolytic stress with 25 mg/kg phenylhydrazine
|
| N |
• no mortality after induction of acute hemolytic stress with high-dose (35 mg/kg) phenylhydrazine
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit markedly darkened ears relative to control mice
|
|
• mice exhibit markedly darkened hair relative to control mice
|
|
• mice exhibit markedly darkened footpads relative to control mice
• Kitl mRNA expression is increased 5.5-fold in the footpad epidermis relative to control mice
|
|
• mice exhibit markedly darkened tails relative to control mice
|
|
• mice exhibit markedly darkened ears relative to control mice
|
|
• mice exhibit markedly darkened hair relative to control mice
|
|
• mice exhibit markedly darkened footpads relative to control mice
• Kitl mRNA expression is increased 5.5-fold in the footpad epidermis relative to control mice
|
|
• mice exhibit markedly darkened tails relative to control mice
|
|
• mice exhibit markedly darkened footpads relative to control mice
• Kitl mRNA expression is increased 5.5-fold in the footpad epidermis relative to control mice
|
|
• mice exhibit markedly darkened tails relative to control mice
|
|
• mice exhibit markedly darkened ears relative to control mice
|
|
• mice exhibit markedly darkened ears relative to control mice
|
|
• mice exhibit markedly darkened ears relative to control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 7 of 8 mice develop one or more tumors of the mammary gland after the first pregnancy
• mean latency time for spontaneous mammary tumor development is 19.7 +/- 8.6 weeks
• mammary tumors of both untreated and DMBA-treated mice are heterogeneous, including frequent adenocarcinomas, solid carcinomas, papillary carcinomas, and adenosquamous carcinomas, carcinosarcomas and sarcomas
• 67% of mammary tumors from untreated and DMBA-treated mice are estrogen receptor alpha-positive
|
|
• 40% of females exposed to DMBA for 6 weeks develop mammary tumors, with a mean latency time of 8.5 +/- 4.7 weeks
• females exposed to DMBA also develop lymphomas, ovary, lung, stomach, uterus and skin tumors
|
|
• some mice develop an additional lymphoma
|
|
• some mice develop an additional sarcoma in the abdomen
|
|
• some mice develop an additional tumor of the lung
|
|
• premature death, with only 2 of 11 mice surviving past 78 weeks
|
|
• 7 of 8 mice develop one or more tumors of the mammary gland after the first pregnancy
• mean latency time for spontaneous mammary tumor development is 19.7 +/- 8.6 weeks
• mammary tumors of both untreated and DMBA-treated mice are heterogeneous, including frequent adenocarcinomas, solid carcinomas, papillary carcinomas, and adenosquamous carcinomas, carcinosarcomas and sarcomas
• 67% of mammary tumors from untreated and DMBA-treated mice are estrogen receptor alpha-positive
|
|
• 40% of females exposed to DMBA for 6 weeks develop mammary tumors, with a mean latency time of 8.5 +/- 4.7 weeks
• females exposed to DMBA also develop lymphomas, ovary, lung, stomach, uterus and skin tumors
|
|
• 7 of 8 mice develop one or more tumors of the mammary gland after the first pregnancy
• mean latency time for spontaneous mammary tumor development is 19.7 +/- 8.6 weeks
• mammary tumors of both untreated and DMBA-treated mice are heterogeneous, including frequent adenocarcinomas, solid carcinomas, papillary carcinomas, and adenosquamous carcinomas, carcinosarcomas and sarcomas
• 67% of mammary tumors from untreated and DMBA-treated mice are estrogen receptor alpha-positive
|
|
• some mice develop an additional tumor of the lung
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:101617 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• phenotypes are relative to the control KPC (KrasG12D/+, p53R172H/+, Pdx1-Cre) PDAC (pancreatic adenocarcinoma) model mice
• size of PDAC primary tumors same as control
|
|
• significantly reduced number of detectable PDAC metastases to liver, lung and other tissues
• reduced migration of PDAC cells in vitro
|
| N |
• survival same as control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• skin tumors develop between 500 and 600 days
• UVB exposure results in 6.5+/-1.4 tumors at day 100 compared to 0.6+/-0.2 in wild-type mice
• whether spontaneous or induced, mice develop epithelial, proliferative lesions forming a continuum from nonneoplastic squamous keratosis and acanthosis to squamous cell papillomas, actinic keratosis and keratoacanthoma with increasing degrees of atypia and dysplasia, carcinoma in situ, up to invasive squamous cell carcinoma
|
|
• one mouse developed a hemangiosarcoma in the intestine
|
|
• developed in one mouse
|
|
• fewer CASP3+ cells area found following UVB treatment when compared to wild-type mice
• the reduction in apoptotic cells is slightly greater in homozygotes than in heterozygotes
|
|
• skin tumors develop between 500 and 600 days
• UVB exposure results in 6.5+/-1.4 tumors at day 100 compared to 0.6+/-0.2 in wild-type mice
• whether spontaneous or induced, mice develop epithelial, proliferative lesions forming a continuum from nonneoplastic squamous keratosis and acanthosis to squamous cell papillomas, actinic keratosis and keratoacanthoma with increasing degrees of atypia and dysplasia, carcinoma in situ, up to invasive squamous cell carcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• accelerated tumor associated mortality relative to control mice
|
|
• mice develop breast tumors similar to control mice
|
|
• liver metastases observed in 3/5 mice as compared to 0/7 relative to control mice
|
|
• liver metastases observed in 3/5 mice as compared to 0/7 relative to control mice
|
|
• mice develop breast tumors similar to control mice
|
|
• mice develop breast tumors similar to control mice
|
|
• liver metastases observed in 3/5 mice as compared to 0/7 relative to control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die 14 weeks or less after tamoxifen administration
|
|
• at 6-8 weeks of age, animals administered 1dose or 4 doses of tamoxifen develop widespread adenomas in the alveoli by 14 weeks of age, but the bronchoalveolar duct junction remains tumor-free
|
|
• at 6-8 weeks of age, animals administered 1dose or 4 doses of tamoxifen develop widespread adenocarcinomas in the alveoli by 14 weeks of age
|
|
• at 6-8 weeks of age, animals administered 1dose or 4 doses of tamoxifen develop widespread adenomas in the alveoli by 14 weeks of age, but the bronchoalveolar duct junction remains tumor-free
|
|
• at 2 weeks after tamoxifen treatement, brochioalveolar duct junctions (BADJ) appear normal, but small adenomas occur in the alveoli; these progress to adenocarcinoma but the BADJ remain histologically normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animal succumb due to tumor burden at 20-24 weeks
|
|
• at 6-8 weeks of age, animals administered 4 doses of tamoxifen develop adenomas in the alveoli by 15 weeks; these progress to adenocarcinomas
• papillary adenomas are seen in alveoli at 15 and 21 weeks after tamoxifen treatment
|
|
• develop in alveoli and near the bronchioalveolar duct junction by 15 weeks of age with tamoxifen administration at 6-8 weeks
• larger bronchioles and non terminal bronchi appear normal
• advanced papillary adenocarcinomas are observed at 21 weeks after tamoxifen treatment
|
|
• at 6-8 weeks of age, animals administered 4 doses of tamoxifen develop adenomas in the alveoli by 15 weeks; these progress to adenocarcinomas
• papillary adenomas are seen in alveoli at 15 and 21 weeks after tamoxifen treatment
|
|
• hyperplasia is observed at 3 weeks after tamoxifen induction, and persists at 15 and 21 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 6-8 months of age, 8 of 11 females developed mammary gland tumors that exhibited several distinct histopathologies
|
|
• by 6-8 months of age, 8 of 11 females developed mammary gland tumors that exhibited several distinct histopathologies
|
|
• by 6-8 months of age, 8 of 11 females developed mammary gland tumors that exhibited several distinct histopathologies
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:54533 | |
| hereditary breast ovarian cancer syndrome | DOID:5683 | J:54533 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen
|
|
|
• mutants exposed to estrogen exhibit an increase in the number of hyperplastic alveolar nodules per mammary gland compared to mutants with wild-type Trp53 and also an increase in the percentage of mice with hyperplastic alveolar nodules
|
|
• 25% of mutants develop invasive mammary cancer when exposed to exogenous estrogen
• cancers are Esr1-negative
|
|
• 25% of mutants develop invasive mammary cancer when exposed to exogenous estrogen
• cancers are Esr1-negative
|
|
• mutants develop mammary gland preneoplasia that are Esr1-negative
|
|
• 25% of mutants develop ureteral obstruction 1-3 months after estrogen pellet placement
|
|
|
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen
|
|
|
• mutants exposed to estrogen exhibit an increase in the number of hyperplastic alveolar nodules per mammary gland compared to mutants with wild-type Trp53 and also an increase in the percentage of mice with hyperplastic alveolar nodules
|
|
• 25% of mutants develop invasive mammary cancer when exposed to exogenous estrogen
• cancers are Esr1-negative
|
|
|
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary breast ovarian cancer syndrome | DOID:5683 | J:132088 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mutants develop hyperplastic alveolar nodules
|
|
• 100% of mutants develop invasive mammary cancer
• some cancers are Esr1-negative while others are Esr1-positive
|
|
• 100% of mutants develop invasive mammary cancer
• some cancers are Esr1-negative while others are Esr1-positive
|
|
• mutants develop mammary gland preneoplasia
• some preneoplasia are Esr1-negative while others are Esr1-positive
|
|
|
• mutants develop hyperplastic alveolar nodules
|
|
• 100% of mutants develop invasive mammary cancer
• some cancers are Esr1-negative while others are Esr1-positive
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hereditary breast ovarian cancer syndrome | DOID:5683 | J:132088 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• occasionally, pulmonary metastasis is seen in the lungs
|
|
• mice develop bone tumors as early as 7 months of age, with incidence significantly increased at 11 months onwards with about 70% penetrance
• bone tumors are located mostly in the forelimbs and hindlimbs and frequently in the spine and are found less frequently in the ribs and skull
• primary tumors are composed of highly mineralized tissues and abundant osteoids with multinucleated cells resembling human osteoblastic osteosarcoma
• the majority of mutants develop only bone tumors
|
|
• mice develop bone tumors as early as 7 months of age, with incidence significantly increased at 11 months onwards with about 70% penetrance
• bone tumors are located mostly in the forelimbs and hindlimbs and frequently in the spine and are found less frequently in the ribs and skull
• primary tumors are composed of highly mineralized tissues and abundant osteoids with multinucleated cells resembling human osteoblastic osteosarcoma
• the majority of mutants develop only bone tumors
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:214349 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 26 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
• average survival time is 143 days, with a range of 91-191 days
|
|
• 26 of 30 mutants develop pancreatic ductal adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• phenotypes are relative to the control KPC (KrasG12D/+, p53R172H/+, Pdx1-Cre) PDAC (pancreatic adenocarcinoma) model mice
• size of PDAC primary tumors same as control
|
|
• significantly reduced number of detectable PDAC metastases to liver, lung and other tissues
• reduced migration of PDAC cells in vitro
|
|
• survival reduced compared to control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after RU486 and TPA treatment, 30% of mice develop skin carcinomas compared to 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after RU486 and TPA treatment, mice develop three-fold more tumors than Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
|
|
• after RU486 and TPA treatment, 60% of mice develop metastasis in the lungs and/or lymph nodes compared to no wild-type mice
|
|
• after RU486 and TPA treatment, 42% of tumors exhibit aneuplody compared to 23% of Krastm4Tyj Trp53tm1Brn heterozygotes and 20% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, tumors exhibit centrosome amplification in 3% to 5% of tumors cells
|
|
• after RU486 and TPA treatment, carcinoma development is accelerated compared to in Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
• after RU486 and TPA treatment, 90% of mice develop skin carcinomas compared to 30% of Krastm4Tyj Trp53tm1Brn heterozygotes and 5% of Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
|
|
• after RU486 and TPA treatment, tumors exhibit centrosome amplification in 3% to 5% of tumors cells
|
|
• after RU486 and TPA treatment, mice develop three-fold more tumors than Krastm4Tyj Trp53tm1Brn heterozygotes and Krastm4Tyj Tg(KRT5-cre/PGR)1Der heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced pancreatic intraepithelial neoplasia incidence and tumor size compared with Krasem1Gpt/ Kras+ Tg(Pdx1-cre)89.1Dam mice
|
|
• reduced pancreatic intraepithelial neoplasia incidence and tumor size compared with Krasem1Gpt/ Kras+ Tg(Pdx1-cre)89.1Dam mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
|
|
• in mice with advanced tumors
|
|
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:64364 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival for the combined population of both males and females is 504 days, i.e., similar to that of mice heterozygous for Trp53 tm3.1Glo alone (499 days)
• median survival is 539 days for male mice and 488 days for female mice, indicating that loss of a single Pml allele does not reduce the mean survival of either male or female Trp53 tm3.1Glo heterozygotes
|
|
|
• average survival of male mice that present with soft tissue sarcomas (42%) is 443 days
|
|
• when tumors are segregated by sex, 33% of males and 42% of females exhibit lymphomas (expressed as a % disease/total number of mice)
• 43% of mice develop lymphomas (when expressed as a % of tumor type); 14% of mice develop two tumor types, lymphomas and sarcomas
• 38% of mice exhibit lymphomas when tumor incidence is evaluated per mouse, including those that succumb to EMH, and expressed as a % disease/total number of mice
|
|
• ~20% of lymphoid tumors are T-cell lymphomas
|
|
• immunophenotyping of lymphocytes from terminally resected tumors showed that ~80% of lymphoid tumors are B-cell lymphomas
|
|
• 5% of mice develop carcinomas (when expressed as a % of tumor type)
(J:317504)
• 4% of mice exhibit carcinomas (when expressed as a % disease/total number of mice)
(J:317504)
|
|
|
|
• when tumors are segregated by sex, 0% of males and 8% of females exhibit carcinomas (expressed as a % disease/total number of mice)
(J:317504)
|
|
• when tumors are segregated by sex, 42% of males and 17% of females exhibit soft-tissue sarcomas (expressed as a % disease/total number of mice)
• 52% of mice develop sarcomas (when expressed as a % of tumor type); 14% of mice develop two tumor types, lymphomas and sarcomas
• 46% of mice exhibit sarcomas (when expressed as a % disease/total number of mice)
|
|
• when tumors are segregated by sex, 8% of males and 25% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)
|
|
• ~20% of lymphoid tumors are T-cell lymphomas
|
|
• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 tm3.1Glo alone
|
|
• when segregated by sex, 33% of males and 33% of females exhibit EMH
• 33% mice exhibit extramedullary hematopoiesis (EMH)
|
|
• ~20% of lymphoid tumors are T-cell lymphomas
|
|
• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 tm3.1Glo alone
|
|
• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 tm3.1Glo alone
|
|
• average body weight is significantly lower than that in C57BL/6 wild-type controls
|
|
• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 tm3.1Glo alone
|
|
• when tumors are segregated by sex, 8% of males and 25% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)
|
|
• ~20% of lymphoid tumors are T-cell lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival for the combined population of both males and females is 448 days, i.e., ~50 days shorter than in mice heterozygous for Trp53 tm3.1Glo alone (499 days) and in mice heterozygous for both Trp53 tm3.1Glo and Pmltm1Ppp (504 days)
(J:317504)
|
|
|
|
• strikingly, median survival is 414 days for male mice, i.e., >100 days shorter than in males heterozygous for Trp53 tm3.1Glo alone (515 days) and in males heterozygous for both Trp53 tm3.1Glo and Pmltm1Ppp (539 days)
(J:317504)
• average survival of male mice with soft tissue sarcomas (44%) is 380 days, i.e., even shorter than in males heterozygous for both Trp53 tm3.1Glo and Pmltm1Ppp (443 days) which develop soft tissue sarcomas with a similar frequency (42%)
(J:317504)
• however, median survival for female mice is 485 days, i.e., not significantly different from that in males heterozygous for Trp53 tm3.1Glo alone (515 days)
(J:317504)
|
|
• when tumors are segregated by sex, 44% of males and 44% of females exhibit lymphomas (expressed as a % disease/total number of mice)
• 36% of mice develop lymphomas (when expressed as a % of tumor type); 18% of mice develop two tumor types, lymphomas and sarcomas
• 44% of mice exhibit lymphomas when tumor incidence is evaluated per mouse and expressed as a % disease/total number of mice
|
|
• ~40% of lymphoid tumors are T-cell lymphomas
|
|
• immunophenotyping of lymphocytes from terminally resected tumors showed that ~60% of lymphoid tumors are B-cell lymphomas
|
|
• 5% of mice develop carcinomas (when expressed as a % of tumor type)
(J:317504)
• 6% of mice exhibit carcinomas (when expressed as a % disease/total number of mice)
(J:317504)
|
|
|
|
• when tumors are segregated by sex, 0% of males and 11% of females exhibit carcinomas (expressed as a % disease/total number of mice)
(J:317504)
|
|
• when tumors are segregated by sex, 44% of males and 11% of females exhibit soft-tissue sarcomas (expressed as a % disease/total number of mice), indicating that males lacking PML succumb to aggressive soft tissue sarcomas more frequently than females
• 59% of mice develop sarcomas (when expressed as a % of tumor type); 18% of mice develop two tumor types, lymphomas and sarcomas
• 72% of mice exhibit sarcomas (when expressed as a % disease/total number of mice)
|
|
• when tumors are segregated by sex, 33% of males and 56% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)
• although osteosarcomas are proportionately more abundant in female mice, survival latency is not significantly altered
|
|
• ~40% of lymphoid tumors are T-cell lymphomas
|
|
• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 tm3.1Glo alone
|
|
• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 tm3.1Glo alone
|
|
• ~40% of lymphoid tumors are T-cell lymphomas
|
|
• when tumors are segregated by sex, 33% of males and 56% of females exhibit osteosarcomas (expressed as a % disease/total number of mice)
• although osteosarcomas are proportionately more abundant in female mice, survival latency is not significantly altered
|
| N |
• when segregated by sex, neither male nor female mice exhibit EMH
• zero of 18 mice (0%) exhibit extramedullary hematopoiesis (EMH)
|
|
• ~40% of lymphoid tumors are T-cell lymphomas
|
|
• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 tm3.1Glo alone
|
| N |
• average body weight is not significantly different from that in C57BL/6 wild-type controls
|
|
• mice exhibit less severe hepatosplenomegaly than mice heterozygous for Trp53 tm3.1Glo alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• overall survival is reduced relative to mice homozygous for Mdm2tm4.1Glo and heterozygous for Trp53 tm3.1Glo
|
|
• in the thymus following a low dose of IR radiation compared to mice homozygous for Mdm2tm4.1Glo and heterozygous for Trp53tm3.1Glo
|
|
• accelerated tumor onset relative to mice homozygous for Mdm2tm4.1Glo and heterozygous for Trp53 tm3.1Glo
• the tumor spectrum is also altered relative to mice homozygous for Mdm2tm4.1Glo and heterozygous for Trp53 tm3.1Glo
• mice develop multiple primary tumors
|
|
• in 1 mouse
|
|
• in 1 mouse
|
|
• salivary carcinoma in 1 mouse
• undefined carcinomas are also reported
|
|
• in 1 mouse
|
|
• soft tissue sarcoma
• chondrosarcoma in 1 mouse
|
|
• in 1 mouse
|
|
• ovarian
|
|
• squamous cell papilloma in 1 mouse
|
|
• in 1 mouse
|
|
• in 1 mouse
|
|
• in 1 mouse
|
|
• in 1 mouse
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 1 mouse
|
|
• an undefined carcinoma is reported in 1 mouse
|
|
• undefined adenocarcinomas are reported
|
|
• in 1 mouse
|
|
• soft tissue sarcoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• develop sarcomas and brain tumors as early as 15 weeks of age
|
|
• mice that develop malignant tumors die by 26 weeks of age
|
|
• 11 of 19 (57.9%) mice develop malignant tumors and die by 26 weeks of age
|
|
• develop sarcomas and brain tumors as early as 15 weeks of age
|
|
• develop sarcomas and brain tumors as early as 15 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 50% of mice develop carcinomas over a period of 460 days which is an increased incidence compared to mice heterozygous for the Trp53 mutation alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• motor coordination is similar to Trp53 heterozygous controls
|
| N |
• no bone marrow deficiencies are detected
|
| N |
• no cerebellar deficiencies are detected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit reduced survival compared to heterozygous Col1a1tm1(tetO-URI1)Ndj Tg(Cebpb-tTA)#Bjd/0 mice
|
|
• mice exhibit accelerated liver tumorigenesis compared to single heterozygous Col1a1tm1(tetO-URI1)Ndj Tg(Cebpb-tTA)#Bjd/0 mice, with 80% of mice showing aggressive hepatocellular carcinoma
|
|
• 8 week old mice show decreased cleaved caspase 3, Bax expression, collapsed fibers, Sirius Red staining and alanine transaminase levels, indicating suppressed hepatocyte apoptosis
|
|
• mice exhibit accelerated liver tumorigenesis compared to single heterozygous Col1a1tm1(tetO-URI1)Ndj Tg(Cebpb-tTA)#Bjd/0 mice, with 80% of mice showing aggressive hepatocellular carcinoma
|
|
• 8 week old mice show decreased cleaved caspase 3, Bax expression, collapsed fibers, Sirius Red staining and alanine transaminase levels, indicating suppressed hepatocyte apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased incidence of induced hepatocellular carcinoma after CCl4 treatment in late generation (G3/4) homozygous mice compared to mice with no p53 mutation
|
|
• increased incidence of induced hepatocellular carcinoma after CCl4 treatment in late generation (G3/4) homozygous mice compared to mice with no p53 mutation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
|
|
• in mice with advanced tumors
|
|
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:64364 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
|
|
• in mice with advanced tumors
|
|
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:64364 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:64364 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice that survive the perinatal period die at ~6 months of age
|
|
• mice are less robust and often die perinatally of indeterminate causes
|
|
• mice do not develop tumors before death at 6 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 5 mice are alive at weaning
|
|
• fewer than expected mice survive to birth
|
|
• fewer than expected mice are alive at E15.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumors exhibit extensive aneuploidy and chromosomal aberrations, notably translocations, chromosome breaks, deletions and dicentric chromosomes
|
|
• mice begin to develop tumors at 5 months of age with tumor incidence reaching 76% by 20 months of age compared to only 2 of 21 Sirt1tm1.1Cxd heterozygotes and 3 of 23 Trp53tm1Brd heterozygotes
• however, treatment of mice with resveratrol decreases the incidence of tumors and delays onset
|
|
• 35% of tumors are lymphomas
|
|
• 16% of tumors are carcinomas
|
|
• 46% of tumors are sarcomas
|
|
• 22% of tumors are teratomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• ex vivo, osteosarcoma-derived cell lines exhibit increased proliferation in BrdU incorporation assays, a higher abundance of tyrosine-phosphorylated proteins, and no cellular growth in response to long-term administration of Mdk (midkine, a heparin-binding growth factor known to antagonize Ptprz1 in other cell types)
|
|
• at 52 weeks of age, 7 of 38 (~19%) mice exhibit osteosarcoma development by contact X-ray analysis
• skeletal tumors are found in three different locations i.e., ribs, spine or long bones, but not in craniofacial bones, and consist of mineralized tissue
• undecalcified histology showed that tumors represent bony tissue with osteocytes embedded into mineralized matrix, confirming their osteosarcoma nature
• cell lines derived from tumors and cultured in the presence of ascorbic acid and beta-glycerophosphate are able to form a mineralized matrix and show differential expression of osteoblast differentiation markers
|
|
• at 52 weeks of age, 7 of 38 (~19%) mice exhibit osteosarcoma development by contact X-ray analysis
• skeletal tumors are found in three different locations i.e., ribs, spine or long bones, but not in craniofacial bones, and consist of mineralized tissue
• undecalcified histology showed that tumors represent bony tissue with osteocytes embedded into mineralized matrix, confirming their osteosarcoma nature
• cell lines derived from tumors and cultured in the presence of ascorbic acid and beta-glycerophosphate are able to form a mineralized matrix and show differential expression of osteoblast differentiation markers
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 52 weeks of age, 2 of 38 (~5%) mice exhibit visible skeletal tumors by contact X-ray analysis
• skeletal tumors are found in three different locations i.e., ribs, spine or long bones, but not in craniofacial bones, and consist of mineralized tissue
• cell lines derived from tumors and cultured in the presence of ascorbic acid and beta-glycerophosphate are able to form a mineralized matrix and show differential expression of osteoblast differentiation markers, confirming their osteosarcoma nature
|
|
• at 52 weeks of age, 2 of 38 (~5%) mice exhibit visible skeletal tumors by contact X-ray analysis
• skeletal tumors are found in three different locations i.e., ribs, spine or long bones, but not in craniofacial bones, and consist of mineralized tissue
• cell lines derived from tumors and cultured in the presence of ascorbic acid and beta-glycerophosphate are able to form a mineralized matrix and show differential expression of osteoblast differentiation markers, confirming their osteosarcoma nature
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3 of 8 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR and Cdk4 develop gliomas compared to 1 of 8 similarly treated wild-type mice
• 17 of 39 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR, Cdk4, and bFGF develop gliomas compared to 3 of 29 similarly treated wild-type mice
• however, mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR do not develop gliomas
|
|
• in mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR, Cdk4, and bFGF
|
|
• 3 of 8 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR and Cdk4 develop gliomas compared to 1 of 8 similarly treated wild-type mice
• 17 of 39 mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR, Cdk4, and bFGF develop gliomas compared to 3 of 29 similarly treated wild-type mice
• however, mice transfected with replication-competent ALV splice acceptor viral vector expressing a constitutively active EGFR do not develop gliomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die prior to 20 weeks of age
|
|
• mice exhibit an earlier age of onset and enhanced penetrance of B cell lymphomas compared to in Tg(IghMyc)22Bri mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the median lifespan of 31 days
|
|
• based on median survival time, mice carrying single Trp53tm1Brd allele were no more resistant to tumor formation induced by myc than mice with homozygous wild-type Ppm1d+ allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• similar to mice with a null Trp53 allele, mice exhibit shorter survival than those with wild-type Trp53
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 22 of 40 mice treated with 2-AAF develop urinary bladder tumors
|
|
• 22 of 40 mice treated with 2-AAF develop urinary bladder tumors
|
|
• 22 of 40 mice treated with 2-AAF develop urinary bladder tumors
|
|
• 22 of 40 mice treated with 2-AAF develop urinary bladder tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% survival at 35 weeks of age
• 50% survival at 26 weeks when irradiated with 5Gy
|
|
• increased incidence of gastric tumors
|
|
• decreased latency for mammary tumor onset
|
|
• increased incidence of osteosarcomas
|
|
• increased incidence of osteosarcomas
|
|
• decreased latency for mammary tumor onset
|
|
• decreased latency for mammary tumor onset
|
|
• increased incidence of gastric tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show a decrease in incidence of metastases compared to double Trp53 and Nf1 heterozygotes, with 19.44% of mice with sarcomas showing metastases compared to 29.4% of double mutants
|
|
• mice show a decrease in incidence of sarcomas compared to double Trp53 and Nf1 heterozygotes, with 13.89% of mice developing soft tissue sarcomas compared to 59.5% of double mutants
• less proliferation is seen in tumors
|
|
• 25% of mice exhibit splenic hyperplasia
|
|
• 25% of mice exhibit splenic hyperplasia
|
|
• 25% of mice exhibit splenic hyperplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by 150 days
|
|
• 12% of mice develop lymphomas
|
|
• 62% of mice develop histiocytic sarcomas
|
|
• 38% of mice develop malignant peripheral nerve sheath tumors
• tumors develop on average at 2.3 months of age
|
|
• 4% of develop angiosarcomas
|
|
• 54% of mice develop high-grade gliomas
• gliomas develop on average at 3 months of age
|
|
• 38% of mice develop malignant peripheral nerve sheath tumors
• tumors develop on average at 2.3 months of age
|
|
• 54% of mice develop high-grade gliomas
• gliomas develop on average at 3 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• osteosarcoma on the lower back and on the skull, with significantly decreased metastasis
• incidence of ibrosarcomas, osteosarcomas, hemangiosarcomas, and histiocytic sarcomas, associated life span, and tumor weight on death are not affected
|
|
• 17% have lymphoma, typical of those observed in Trp53tm1Tyj/+ mice
• 23% have lymphomas, resembling anaplastic large cell lymphomas
• lymphoma is seen in conjunction with osteosarcoma, fibrosarcoma, and histiocytic sarcoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a spectrum of gamma-irradiation-induced tumors intermediate to in Trp53tm1Glo heterozygotes and Cops6Gt(RRI087)Byg heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• small increase in tumor incidence (2/20) after irradiation at P5 or 6 with 4 Gy radiation
|
|
• small increase in tumor incidence (2/20) after irradiation at P5 or 6 with 4 Gy radiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are smaller and less robust than wild-type littermates
|
|
• thymoma is detected
|
|
• thymoma is detected
|
|
• thymoma is detected
|
|
• thymoma is detected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared with Tg(IghMyc)22Bri mice
• median survival is 10 days longer than in Trp53tm1Thst/Trp53+ Tg(IghMyc)22Bri mice
|
|
• with increased apoptosis and senescence staining in tumors from Tg(IghMyc)22Bri mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased tumor incidence compared to wild-type controls but not compared to mice heterozygous for the Trp53 allele alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryonic lethality by E13.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• compared with Tg(IghMyc)22Bri mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no mice are present at 3 weeks of age
|
|
• embryos are abnormal at E9.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• neural crest stem cells do not abnormally persist in the peripheral nervous system in adult mice
|
|
• form by 6 months of age
|
|
• form by 6 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median age of survival is 7 months
|
|
• 40% of mutants exhibit increased signs of aging, developing severe degenerative disc disease of the spine between 6 and 18 months of age
|
|
• about 50% of mutants develop metastatic tumors
|
|
• mutants exhibit an increase in tumor burden compared to heterozygous Trp53 mice, with 90% of mutant mice having multiple tumors of the same or distinct types compared to only 10% in Trp53 heterozygotes
• mutants develop collision tumors composed of mammary adenocarcinomas directly adjacent to squamous cell carcinomas and/or rhabdomyosarcomas
• tumors exhibit loss of heterozygosity of one or both genes
|
|
• 10% of mutants develop thymic lymphomas
|
|
• 10% of mutants develop mammary adenocarcinomas
|
|
• 20% of mutants develop rhabdomyosarcomas
|
|
• 15% of mutants develop myelogenous leukemia
|
|
• 50% of mutants develop squamous cell carcinomas in multiple tissues (larynx, pharynx, cervix, and esophagus)
|
|
• 20% of mutants develop transitional cell carcinoma of the bladder
|
|
• 20% of mutants develop osteosarcomas
|
|
• 20% of mutants develop osteosarcomas
|
|
• 40% of mutants develop severe degenerative disc disease of the spine between 6 and 18 months of age
• degenerative disc disease is consistent with spondylosis and is most frequent in the cervical and thoracic region
|
|
• 10% of mutants develop thymic lymphomas
|
|
• 10% of mutants develop mammary adenocarcinomas
|
|
• 10% of mutants develop mammary adenocarcinomas
|
|
• 20% of mutants develop rhabdomyosarcomas
|
|
• 20% of mutants develop transitional cell carcinoma of the bladder
|
|
• 10% of mutants develop thymic lymphomas
|
|
• 10% of mutants develop thymic lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median age of survival is 6 months
|
|
• about 45% of mutants develop metastatic tumors
|
|
• mutants exhibit an increase in tumor burden compared to heterozygous Trp53 mice, with 75% of mutant mice having multiple tumors of the same or distinct types compared to only 10% in Trp53 heterozygotes
• tumors exhibit loss of heterozygosity of one or both genes
|
|
• 22.5% of mutants develop thymic lymphomas
|
|
• 15% of mutants develop acinar pancreatic carcinoma
|
|
• 15% of mutants develop hepatocellular carcinomas
|
|
• 10% of mutants develop lung adenocarcinomas
|
|
• 50% of mutants develop sarcomas
|
|
• 22.5% of mutants develop thymic lymphomas
|
|
• 15% of mutants develop acinar pancreatic carcinoma
|
|
• 10% of mutants develop lung adenocarcinomas
|
|
• 15% of mutants develop hepatocellular carcinomas
|
|
• 22.5% of mutants develop thymic lymphomas
|
|
• 22.5% of mutants develop thymic lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• aneuploidy frequency in splenocytes is higher (58%) compared to single Map9 heterozygotes (39%) or single p53 heterozygotes (23%) or wild-type mice (17%)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no viable mice are found, no specific time of death is provided
|
|
• reduced in size compared to double heterozygous controls; however, this reduction is slight compared to mice homozygous for the Mdm4 mutation alone
|
|
• reduced in size compared to double heterozygous controls; however, this reduction is slight compared to mice homozygous for the Mdm4 mutation alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants have a median survival of 6.5 months compared to median survival of 10.8 months and 11.7 months of each single heterozygote respectively
|
|
• double heterzygotes show fewer tumors of this type compared with the single heterozygotes
|
|
• doubly heterozygous mice show an increase in metastatic disease compared to single heterozygotes
|
|
• double heterzygotes show fewer tumors of this type compared with the single heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• MEFs grow at a rate between that of heterozygous Trp53 MEFs and wild-type cells, indicating that the senescence seen in homozygous Arhgap1 mutant MEFs is rescued
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• only 20% of the expected number of pups are found at birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• prolonged survival compared to mice heterozygous for the Trp53 allele alone
|
|
• compared to mice heterozygous for the Trp53 allele alone
|
|
• increase in tumor type multiplicity compared to mice heterozygous for the Trp53 allele alone
|
|
• compared to mice heterozygous for the Trp53 allele alone
|
|
• tumors appear at about 13 months of age compared to about 9 months of age in mice heterozygous for the Trp53 allele alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 26% of double heterozygotes develop tumors over a 72 week period
|
|
• lymphoma development is accelerated in compared to Trp53 heterozygotes with wild-type Trp53bp2; at 42 weeks there is a significant difference in the onset between the two genotypes
• at 72 weeks the difference in onset of lymphoma development is not significant
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average lifespan is 266 days with female mice exhibiting shorter lifespans than male mice
|
|
• lung adenocarcinomas and mesothelioma are highly invasive and metastatic with metastatic lesions observed in the lymph nodes and liver
• 19 of 52 mice with lung adenocarcinomas exhibit metastasis compared to only 2 of 44 Krastm2Tyj heterozygotes
|
|
• 81.8% of mice with end-stage lung adenocarcinomas exhibit loss of heterozygosity of the Trp53 wild-type allele
|
|
• mice develop adenocarcinomas, adenomas, lymphomas, mesotheliomas, angiosarcomas, fibrosarcomas, pancreatic carcinomas, squamous carcinomas, and papillomas
|
|
• 52 of 56 mice develop atypical adenamatous hyperplasia, adenomas and adenocarcinomas
• most mice develop multiple large or diffuse adenocarcinomas that have glandular phenotypes or are poorly differentiated
|
|
• some mice develop lung lymphomas
|
|
• 13 of 56 mice develop mesothelioma 6 of which are peritoneal mesotheliomas
|
|
• 52 of 56 mice develop atypical adenamatous hyperplasia, adenomas and adenocarcinomas
• most mice develop multiple large or diffuse adenocarcinomas that have glandular phenotypes or are poorly differentiated
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung cancer | DOID:1324 |
OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210 |
J:129627 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some die within 3 months
|
|
• decreased compared to Trp53tm1.1Tldo/+ mice
|
|
• decreased compared to Trp53tm1.1Tldo/+ mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• less than 5% of mice live past two years due to cancerous tumors
|
|
• mice develop significantly more metastatic tumors than Trp53tm1Tyj heterozygotes (18.2% vs 2.6%)
• metatastic tumors are found in the lung, liver, kidney, and lymph node
• mouse embryonic fibroblasts cells migrate almost as twice as fast as wild-type MEFs through a matrigel membrane
|
|
• mice develop tumors with age similar to Trp53tm1Tyj heterozygotes
• over 95% of mice have tumors by 2 years of age
|
|
• is observed in 4.5% of mice by 24 months of age
|
|
• is observed in 20.5% of mice by 24 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all embryos die between E3.5 and E7.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Approximately 50% die by 10 months of age, significantly sooner than either single heterozygote
|
|
• time to onset of polyposis is similar to single heterozygotes
• 92% of moribund mice between 7 and 14 months of age have gastrointestinal polyps
• polyps are not found before 5.5 months of age, but at 6.5 months are seen in 60% of mice
|
|
• mice have enlarged abdomens due to presence of polyps in pylorus and duodenum
|
|
• polyps are hamartomas
• tumor-free survival rate is about 11 months compared with 17 months for Trp53 single heterozygotes
• 23 of 38 (61%) of double heterozygotes developed a total of 30 tumors
|
|
• 20% (6 of 30) tumors are lymphomas
|
|
• 10% (3 of 30) of the tumors are sarcomas
|
|
• 43% of the tumors (13 of the 30) are osteosarcomas
|
|
• 43% of the tumors (13 of the 30) are osteosarcomas
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Peutz-Jeghers syndrome | DOID:3852 |
OMIM:175200 |
J:104347 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice die before 9 month experimental end-point of 9 months due to development of obvious tumor mass
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Increased apoptosis in the developing central nervous system of Rps7Zma/Rps7+ embryos which is reduced in Rps7Zma/Rps7+ Trp53tm1Tyj/Trp53+ embryos
| N |
• viability is restored compared to in Rps7Zma heterozygotes
|
|
• small belly spot in some mice
|
| N |
• embryonic developmental delay observed in Rps7Zma heterozygotes is suppressed
|
| N |
• erythroid maturation defects observed in Rps7Zma heterozygotes are suppressed
|
|
• small belly spot in some mice
|
| N |
• tail kinks observed in Rps7Zma heterozygotes are suppressed
|
| N |
• neuron apoptosis observed in Rps7Zma heterozygotes is suppressed
|
| N |
• vertebral fusions observed in Rps7Zma heterozygotes are suppressed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most die within 3 months
|
|
• decreased compared to Trp53tm1.1Tldo/+ mice
|
|
• decreased compared to Trp53tm1.1Tldo/+ mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 77.3% of mice develop pancreatic tumors with a mean tumor-free survival of 220 days
• tumors sometimes show loss of heterozygosity for Trp53, Inkra/Arf, and/or Smad4
|
|
• 77.3% of mice develop pancreatic tumors with a mean tumor-free survival of 220 days
• tumors sometimes show loss of heterozygosity for Trp53, Inkra/Arf, and/or Smad4
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic carcinoma | DOID:4905 |
OMIM:260350 |
J:67389 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• weight of ionizing radiation induced thymic lymphomas is increased compared to mutant mice wild-type for Uimc1
|
|
• 78.5% of mice (11 of 14) develop thymic lymphomas after exposure to ionizing radiation
|
|
• 78.5% of mice (11 of 14) develop thymic lymphomas after exposure to ionizing radiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased tumor latency by 10 weeks
• 2-fold increased mammary tumor risk
• increased mammary tumor incidence
• decreased mammary tumor-free survival
|
|
• decreased tumor latency by 10 weeks
• 2-fold increased mammary tumor risk
• increased mammary tumor incidence
• decreased mammary tumor-free survival
|
|
• decreased tumor latency by 10 weeks
• 2-fold increased mammary tumor risk
• increased mammary tumor incidence
• decreased mammary tumor-free survival
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• adult mice exhibit reversal of the hyperpigmentation phenotype seen in the footpad and tail skin of single Rps19Mhdadsk3 heterozygotes
|
| N |
• adult mice exhibit reversal of the body weight phenotypes seen in single Rps19Mhdadsk3 heterozygotes
|
|
• adult mice exhibit reversal of the erythrocyte phenotype seen in single Rps19Mhdadsk3 heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• adult mice exhibit reversal of the hyperpigmentation phenotype seen in the footpad and tail skin of single Rps20Mhdadsk4 heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the mean age of survival of double heterozygotes is slightly reduced relative to mice heterozygous for Rb1tm1Tyj alone (9 months vs 11 months)
|
|
• in nearly all double heterozygotes with pituitary and thyroid tumors, the wild-type allele of Rb1 is lost whereas the wild-type allele of Trp53 is retained
|
|
• one of 7 individual double heterozygotes analyzed displayed a single pinealoblastoma (not detected in single heterozygotes); the wild-type alleles of both Rb1 and Trp53 were lost in this pineal tumor
|
|
• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe
|
|
• ~75% of double heterozygous mice develop medullary thyroid tumors
|
|
• 14% of a total of 14 individual double heterozygotes analyzed displayed islet cell carcinomas (not detected in single heterozygotes)
• notably, the wild-type alleles of both Rb1 and Trp53 were lost in tumors of the islet cells of the pancreas
|
|
• 6% of a total of 67 individual double heterozygotes analyzed displayed anaplastic sarcomas
• such tumors were shown to be more aggressive and arise at an earlier age than those occurring in single Trp53tm1Tyj heterozygotes
• notably, the wild-type alleles of both Rb1 and Trp53 were lost in these anaplastic sarcomas
|
|
• one of 7 individual double heterozygotes analyzed displayed a leiomyosarcoma
|
|
• 8% of a total of 12 individual double heterozygotes analyzed displayed bronchial hyperplasia
|
|
• one of 7 individual double heterozygotes analyzed displayed a leiomyosarcoma
|
|
• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe
|
|
• ~75% of double heterozygous mice develop medullary thyroid tumors
|
|
• 14% of a total of 14 individual double heterozygotes analyzed displayed islet cell carcinomas (not detected in single heterozygotes)
• notably, the wild-type alleles of both Rb1 and Trp53 were lost in tumors of the islet cells of the pancreas
|
|
• each of 67 double heterozygotes analyzed developed pituitary tumors of the intermediate lobe
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most mice die by 250 days
(J:217077)
• median survival time is 5-15 months
(J:228258)
|
|
• 41.2% of mice exhibit splenic hyperplasia
|
|
• metastases are seen in 29.4% of mice with sarcomas
|
|
• 3% of mice develop lymphomas
(J:217077)
• mice develop lymphomas around 3-6 months of age
(J:228258)
|
|
• 10% of mice develop histiocytic sarcomas
|
|
• 8% of mice develop neuroblastoma
|
|
• 59.5% of mice develop soft tissue sarcomas of the limbs and abdomen around 3-6 months of age
|
|
• 67% of mice develop malignant peripheral nerve sheath tumors
• tumors develop on average at 150 days of age
|
|
• 15% of mice develop high-grade glioma
• gliomas develop at approximately 200 days of age
|
|
• 8% of mice develop neuroblastoma
|
|
• 67% of mice develop malignant peripheral nerve sheath tumors
• tumors develop on average at 150 days of age
|
|
• 15% of mice develop high-grade glioma
• gliomas develop at approximately 200 days of age
|
|
• 41.2% of mice exhibit splenic hyperplasia
|
|
• 41.2% of mice exhibit splenic hyperplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean age of survival was 415 days vs. mice heterozygous for Trp53tm1Tyj alone or homozygous Prdm2tm1Shg alone, which survived to ~550 days
|
|
• of types similar to those found in mice homozygous for Prdm2tm1Shg alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• average life span of 426 days
|
|
• 1.6% incidence of pancreatic adenocarcinomas
• 1.6% incidence of islet cell adenocarcinomas
|
|
• 58% of 19 tumors exhibit loss of heterozygosity for Trp53
|
|
• 4.7% incidence
|
|
• 44% incidence
|
|
• 17% incidence
|
|
• 33% incidence
|
|
• 19% incidence of adenocarcinomas
• 1.6% incidence of pancreatic adenocarcinomas
• 1.6% incidence of islet cell adenocarcinomas
|
|
• 4.7% incidence
|
|
• 1.6% incidence of hepatocarcinoma
|
|
• 9.4% incidence
|
|
• 14% incidence of ear squamous cell carcinoma
|
|
• 44% incidence of sarcomas
• 1.6% incidence of undifferentiated sarcomas
|
|
• 13% incidence
|
|
• 13% incidence
|
|
• 1.6% incidence of stomach papilloma
|
|
• 13% incidence of stomach polyps
|
|
• 9.4% incidence
|
|
• 4.7% incidence
|
|
• 1.6% incidence of hepatocarcinoma
|
|
• 13% incidence
|
|
• 4.7% incidence
|
|
• 1.6% incidence of pancreatic adenocarcinomas
• 1.6% incidence of islet cell adenocarcinomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no embryos found at ages E7.5, E9.5, E17.5 and no mice at age P21
• empty decidua found at ages E7.5 and E9.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lymphoid-primed multipotent progenitors are increased compared to in 2810417H13Riktm1.1Lkd homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants develop facial and orbital tumors with lower penetrance than in double homozygous mice
|
|
• double mutants develop facial and orbital tumors with lower penetrance than in double homozygous mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double mutants display more malignant features than Kras heterozygous tumors, with marked cellular pleomorphism and anaplastic changes with giant cell formation
• mice have broader tumor spectrum compared to Kras or Trp53 heterozygotes, including histocytic sarcoma, medulloblastoma, osteosarcoma, and teratoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos show cortical malformations with aberrant folding together with severe cortical dysplasia
|
|
• ssubcortical heterotopias within the neocortex
• heterotopias show the presence of cells with abnormal nuclear morphologies, multilobulated nuclei, or abnormally large nuclei
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lethality around E11.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show a suppression of the cancer phenotype compared to Sds-haploinsufficinet, Trp53-null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike Rbm24tm1.1Xch homozygotes, mice exhibit normal endocardial cushions with rescue of cardiac tissue apoptosis
|
|
• at E18.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median survival is 70 weeks, slightly but not statistically significantly longer than in mutant mice wild-type for Rbm38
|
|
• tumor spectrum is slightly different from mutant mice wild-type for Rbm38
|
|
• 9 of 21 mice do not succumb to tumors compared to 1 of 24 mutant mice wild-type for Rbm38
|
|
• splenic follicular hyperplasia in tumor free mice
|
|
• in tumor free mice
|
|
• splenic follicular hyperplasia in tumor free mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doxycycline-treated mice initiate lung tumors more rapidly than in Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice with a more malignant phenotype
|
|
• more sooner in doxycycline-treated mice compared with Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice
|
|
• doxycycline-treated mice initiate lung tumors more rapidly than in Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice with a more malignant phenotype
|
|
• more sooner in doxycycline-treated mice compared with Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice are present at E12.5
|
|
• no mice are present at weaning
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• no viable mice are born
|
|
|
• at E10.5, embryos show a significant increase in the number of apoptotic cells, as determined by IHC staining for cleaved caspase-3
|
|
|
• at E10.5, embryos show a significant increase in the number of apoptotic cells, as determined by IHC staining for cleaved caspase-3
|
|
|
• at E10.5, embryos exhibit an increase in the proportion of gamma-H2AX-positive cells relative to wild-type embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• more so than in Aktiptm1a(EUCOMM)Hmgu homozygotes with all mice dead before 55 weeks of age
|
| N |
• male fertility observed in Aktiptm1a(EUCOMM)Hmgu homozygotes is rescued
|
| N |
• mouse embryonic fibroblast do not exhibit increased sensitivity to bleomycin or hydroxyurea unlike cells from Aktiptm1a(EUCOMM)Hmgu homozygotes
|
|
• in mouse embryonic fibroblasts
|
|
• multiorgan in all mice
|
|
• after 31 weeks of age but less than in Aktiptm1a(EUCOMM)Hmgu homozygotes
• however, weight up to 24th week is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal glucose serum levels unlike mice expressing the transgene alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• pups are about half the size of heterozygous littermates
|
|
• 3 pups were born alive, out of 33 pups in seven litters, but two died 1 day after birth and the third died at P24
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 7 of 14 mice develop T-lymphoblastic lymphoma
• 1 of 14 mice develop T-cell lymphoma in thymus, lymph node and spleen
|
| N |
• postnatal lethality observed in Rps27lGt(IST11658B7)Tigm homozygotes is rescued
|
|
• mice die sooner than mice with a wild-type allele of Rps271
|
|
• 7 of 14 mice develop T-lymphoblastic lymphoma
• 1 of 14 mice develop T-cell lymphoma in thymus, lymph node and spleen
|
|
• in 1 of 14 mice
|
|
• 7 of 14 mice develop T-lymphoblastic lymphoma
• 1 of 14 mice develop T-cell lymphoma in thymus, lymph node and spleen
|
|
• partially rescued
|
|
• in lymphoma cells and mouse embryonic fibroblasts
|
| N |
• growth retardation and organ hypocellularity (spleen, thymus and bone marrow) observed in Rps27lGt(IST11658B7)Tigm homozygotes is rescued
|
|
• 7 of 14 mice develop T-lymphoblastic lymphoma
• 1 of 14 mice develop T-cell lymphoma in thymus, lymph node and spleen
|
|
• in 1 of 14 mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• incidence is reduced to 58% compared to 100% in mice homozygous for the Pax3 mutation alone
|
|
• incidence is reduced to 58% compared to 100% in mice homozygous for the Pax3 mutation alone
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mammary tumors start to develop at 6 months of age
• 70% of mice have developed tumors by 18 months of age
|
|
• 25% of mammary epithelial cells from 4-month old mice are polyploidy and show premature chromatid segregation
• about half of mammary epithelial tumor cells are polyploidy
|
|
|
• 10% of mammary epithelial cells from 4-month old mice contain more than 2 centrosomes per nucleus compared to about 1% mammary epithelial cells from control mice
|
|
|
• parous mice over one year in age have more extensive ductal branching than transgenic mice not carrying a mutant Trp53 allele
|
|
|
• parous mice have almost 6-fold more actively proliferating cells in the mammary epithelium than in controls
|
|
• mammary tumors start to develop at 6 months of age
• 70% of mice have developed tumors by 18 months of age
|
|
|
• 10% of mammary epithelial cells from 4-month old mice contain more than 2 centrosomes per nucleus compared to about 1% mammary epithelial cells from control mice
|
|
|
• parous mice over one year in age have more extensive ductal branching than transgenic mice not carrying a mutant Trp53 allele
|
|
|
• parous mice have almost 6-fold more actively proliferating cells in the mammary epithelium than in controls
|
|
• mammary tumors start to develop at 6 months of age
• 70% of mice have developed tumors by 18 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| breast cancer | DOID:1612 |
OMIM:114480 |
J:145680 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• survival to birth is normal
|
|
• increased sensitivity to paraquat induced lethality
|
|
• die shortly after developing respiratory difficulty
|
| N |
• normal mammary gland development
|
|
• seen on autopsy of mice that die prematurely
• enlarged thymus takes up most of the free space in the thorax
|
|
• develop in many mice
• lymphomas display a loss of heterozygocity at the Trp53 locus
• lymphoma cells display aneuploidy
• various chromosomal aberrations such as double minute chromosomes are greatly increased in frequency
|
|
• develop mammary gland tumors by 6-10 months of age
|
|
• develop in many mice
• lymphomas display a loss of heterozygocity at the Trp53 locus
• lymphoma cells display aneuploidy
• various chromosomal aberrations such as double minute chromosomes are greatly increased in frequency
|
|
• develop mammary gland tumors by 6-10 months of age
|
|
• increased incidence of esophageal tumors when treated with methyl N-amylnitrosamine
|
|
• stomach and esophageal dysplasia and carcinomas at 8 month
• invasive carcinomas at 8-12 months
|
|
• partial or complete loss of G1 to S checkpoint control
|
|
• in E14.5 embryos but still less than when both Trp53 alleles are normal
|
|
• embryonic fibroblasts (MEFs) grow better in culture than when both Trp53 alleles are normal
|
|
• seen on autopsy of mice that die prematurely
• enlarged thymus takes up most of the free space in the thorax
|
|
• develop in many mice
• lymphomas display a loss of heterozygocity at the Trp53 locus
• lymphoma cells display aneuploidy
• various chromosomal aberrations such as double minute chromosomes are greatly increased in frequency
|
|
• develop breathing difficulties and become sick
|
|
• hyperkeratosis at 6 months
• increased cell proliferation in the basal layers
• hyperplasia and metaplasia at 6 months
• dysplasia and carcinomas at 8 months
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|
• hyperkeratosis of the forestomach at 6 months
• increased cell proliferation in the basal layers
• hyperplasia and metaplasia at 6 months
• dysplasia and carcinomas at 8 months
|
|
• increased sensitivity to paraquat induced lethality
|
|
• increased incidence of esophageal tumors when treated with methyl N-amylnitrosamine
|
|
• seen on autopsy of mice that die prematurely
• enlarged thymus takes up most of the free space in the thorax
|
|
• develop in many mice
• lymphomas display a loss of heterozygocity at the Trp53 locus
• lymphoma cells display aneuploidy
• various chromosomal aberrations such as double minute chromosomes are greatly increased in frequency
|
|
• in E14.5 embryos but still less than when both Trp53 alleles are normal
|
|
• develop mammary gland tumors by 6-10 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• majority of mice die at less than 8 weeks of age, with a significant drop in survival at ~3 weeks of age
|
|
• embryonic lethality is dramatically abrogated in double mutants (20/369 double null offspring) compared to nearly total lethality with Lig4-deficiency alone (8/369 observed)
• numbers of double heterozygotes observed are similar to expected numbers
|
|
• postnatally, mice are much smaller (only 25% of control littermate weight) than wild-type or doubly-heterozygous littermates
|
|
• neuronal apoptosis is significantly rescued with Trp53 haploinsufficiency
|
|
• neuronal apoptosis is significantly rescued with Trp53 haploinsufficiency
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 30% of males die of lymphoma by 7 months of age
• most males are dead by 12 months of age
|
|
• 8 month and older males develop aging phenotypes
• aging phenotypes also seen in female mice
|
|
• greatly reduced body weight
|
|
• loss of trabecular bone
|
|
• reduced anaesthetic stress tolerance
|
|
• reduced re-epithelialization at wound edges
|
|
• reduced subcutaneous adipose tissue
|
|
• adipose tissue generally reduced
|
|
• increased tumorigenesis in females
|
|
• homologous chromosomes synapse but fail to separate
|
|
|
• apoptotic spermatocytes in seminiferous tubules increased at 16 and 21 days of age relative to controls
|
|
|
• significantly smaller than controls at 16 days of age
|
|
|
• males over six weeks of age lack spermatozoa in the testes
• testes histologically normal at 10 days
|
|
|
• no spermatids present at 21 days of age
|
|
|
• no diplotene stage spermatocytes detected at 16 days of age
|
|
|
• spermatogenesis does not progress beyond meiosis I
• spermatocytes do not pass through pachytene stage
|
|
|
• significantly smaller than controls at 16 days of age
|
|
|
• males over six weeks of age lack spermatozoa in the testes
• testes histologically normal at 10 days
|
|
|
• no spermatids present at 21 days of age
|
|
|
• no diplotene stage spermatocytes detected at 16 days of age
|
|
|
• spermatogenesis does not progress beyond meiosis I
• spermatocytes do not pass through pachytene stage
|
|
• homologous chromosomes synapse but fail to separate
|
|
|
• apoptotic spermatocytes in seminiferous tubules increased at 16 and 21 days of age relative to controls
|
|
• of MEFs
|
|
• reduced subcutaneous adipose tissue
|
|
• reduced hair regeneration
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no viable mice are produced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mice die prior to weaning
|
|
• defects in development are less severe than in Dp(4D4Mit190-D4Mit51)1AAM heterozygotes
|
|
• some mice are runted
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 45 out of 74 mice develop tumors compared to 31 out of 63 mice in littermate controls
• tumors differ in their type and location, and include lymphomas, sarcomas, plasmacytomas and others
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 59 out of 104 mice develop tumors compared to 31 out of 63 mice in littermate controls
• tumors differ in their type and location, and include lymphomas, sarcomas, plasmacytomas and others
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 20 weeks, mice develop gastric hamartomas unlike wild-type mice
• at 24 weeks, all mice develop gastric hamartomas unlike wild-type mice
• hamartomas are composed of glandular and cystic epithelial layers without dysplastic signs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants exhibit a tumor incidence similar to that of single hemizygous Tg(Th-MYCN)41Waw mice
|
|
• mutants exhibit a tumor incidence similar to that of single hemizygous Tg(Th-MYCN)41Waw mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neuroblastoma | DOID:769 | J:41126 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer transgenic mice develop skin tumors after topical application of DMBA and PMA than Trp53 heterozygote controls
• median time to tumor formation is 25 weeks versus 16 weeks for the Trp53 heterozygote controls
• a lower percentage of mice (71% versus 89%) have tumors 32-weeks after DMBA application compared with controls
• mean tumor burden is 2.29 tumors per mouse compared to 3.0 tumors in controls
• tumor regression is not observed in transgenic mice whereas 10% of tumors in non-transgenic mice regress
• transgenic mice have an increased incidence of atypical papillomas that progress to squamous cell carcinoma
|
|
• fewer transgenic mice develop skin tumors after topical application of DMBA and PMA than Trp53 heterozygote controls
• median time to tumor formation is 25 weeks versus 16 weeks for the Trp53 heterozygote controls
• a lower percentage of mice (71% versus 89%) have tumors 32-weeks after DMBA application compared with controls
• mean tumor burden is 2.29 tumors per mouse compared to 3.0 tumors in controls
• tumor regression is not observed in transgenic mice whereas 10% of tumors in non-transgenic mice regress
• transgenic mice have an increased incidence of atypical papillomas that progress to squamous cell carcinoma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a reduction in sunburn cells associated with UVB-irradiation compared to wild-type mice and Trp53 heterozygotes but do not exhibit as much of a reduction as in Trp53 homozygotes
|
|
• mice exhibit a reduction in skin cell apoptosis associated with UVB-irradiation compared to wild-type mice or Trp53 null mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• females display focal changes including cystic follicles and mild changes in the adjacent interfollicular epithelium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die between 9 and 12 months
|
|
• mice develop epithelial carcinomas such as lung, liver, breast, and gastrointestinal cancers
|
|
• 18% of tumors
|
|
|
• 9% of tumors
|
|
• 27% of tumors
|
|
• 27% of tumors
|
|
• mice develop epithelial carcinomas such as lung, liver, breast, and gastrointestinal cancers
|
|
• 27% of tumors
|
|
|
• 9% of tumors
|
|
• 18% of tumors
|
|
• 18% of tumors
|
|
|
• 9% of tumors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• life span is shorter compared to littermates with only a single gene defect
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 80% of mice die within 6 months of high grade oligodendroglioma
|
|
• mice develop gliomas as in Cdkn2atm1Rdp/Cdkn2atm1Rdp Tg(S100b-v-erbB)4496Waw mice with loss of function of the wild-type Trp53 allele
|
|
• 80% of mice die within 6 months of high grade oligodendroglioma
|
|
• mice develop gliomas as in Cdkn2atm1Rdp/Cdkn2atm1Rdp Tg(S100b-v-erbB)4496Waw mice with loss of function of the wild-type Trp53 allele
|
|
• 80% of mice die within 6 months of high grade oligodendroglioma
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| oligodendroglioma | DOID:3181 | J:82649 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lifespan is ~8 months due to sarcomas
|
|
• all mice develop sarcoma outgrowth within the fibrovascular response
• tumors 1-1.5 cm in diameter and are composed of spindled, anaplastic cells and scattered giant cells
|
|
• vascular, fibrotic dermis
|
|
• between 6 and 8 months of age, dorsal skin lesions similar to those in the inducible models develop in all animals
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• eye size is increased compared to in Tg(Cryaa-NCOA6*)AD5Cve mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cis-double heterozygotes died at 15 weeks and trans-double heterozygotes died at 25 weeks
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• both cis- and trans-double heterozygotes developed sarcomas
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
|
• developed in cis-double heterozygotes
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neurofibromatosis 1 | DOID:0111253 |
OMIM:162200 |
J:58877 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• only 1 of 17 (5.9%) mice develop a tumor, a spindle cell tumor compared to 57.9% of double heterozygous Nf1 and Trp53 mutants; this mouse was sacrificed at 21 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• four triple mutants were found to be exencephalic, whereas none were found to be wild-type for Trp53
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die prior to 20 weeks of age
|
|
• mice exhibit an earlier age of onset and enhanced penetrance of B cell lymphomas compared to in Tg(IghMyc)22Bri mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cis-double heterozygotes die by 5 months of age and trans-double heterozygotes survive to the average age of 10 months
|
|
• cis-double heterozygotes exhibit greater incidence of tumors than trans-double heterozygotes
|
|
• developed in both cis- and trans-double heterozygotes
• sarcomas in trans-double heterozygotes were similar to those found in mice with either single mutation and were usually correlated with loss of one chromosome
|
|
• develop in cis-double heterozygotes, usually correlated with loss of one chromosome
|
|
• develop in cis-double heterozygotes, usually correlated with loss of one chromosome
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neurofibromatosis 1 | DOID:0111253 |
OMIM:162200 |
J:58876 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased embryonic lethality
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• within 10 weeks of electroporation of a cre expression vector into the muscles of the lower right leg, soft tissue tumors of the lower right leg develop in 40% of mice
|
|
• tumors are of this type
|
|
• tumors are of this type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• unlike single Pole4tm1(KOMP)Vlcg homozygotes, which are essentially embryonic lethal in the inbred C57BL/6 background, mice are born at slightly sub-Mendelian ratios (10.1% born versus 12.5% expected)
|
|
• loss of rotarod coordination, observed in single Pole4tm1(KOMP)Vlcg homozygotes, is not rescued by deleting a single Trp53 allele
|
|
• ~90% of mice present with lymphomas
|
|
• ~90% of mice present with lymphomas
|
|
• ~90% of mice present with lymphomas
|
|
• lymphoma-free survival is significantly reduced to 226 days relative to 480 days in Trp53tm1Brd heterozygotes, indicating accelerated tumorigenesis
|
|
• ~90% of mice present with lymphomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
|
|
• in mice with advanced tumors
|
|
• brain tumors range from diffuse cells with nuclear atypia to glioblastoma multiforme
• Background Sensitivity: mice on a congenic C57BL/6 or C3H/HeJ F1 background develop more brain tumors compared with mice on a CAST/EiJ or SJL/J F1 background
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant astrocytoma | DOID:3069 | J:64364 | ||
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 03/18/2025 MGI 6.24 |
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