Analysis Tools|
Allele Symbol Allele Name Allele ID |
Rb1tm3Tyj targeted mutation 3, Tyler Jacks MGI:2450162 |
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| Summary |
35 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adult liver cells of mice injected intrasplenically with an adenovirus expressing Cre recombinase exhibit an increase in polyploidy
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| N |
• mice injected intrasplenically with an adenovirus expressing Cre recombinase do not develop liver tumors
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decreased tumor free survival time
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tumor free survival time is increased compared to mutant mice wild-type for Sox2
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• compared to mutant mice wild-type for Sox2
• tumors are uniformly Sox2 positive
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• compared to mutant mice wild-type for Sox2
• tumors are uniformly Sox2 positive
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• tumor free survival time is increased compared to mutant mice wild-type for Sox2
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• compared to mutant mice wild-type for Sox2
• tumors are uniformly Sox2 positive
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• compared to mutant mice wild-type for Sox2
• tumors are uniformly Sox2 positive
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adeno-cre-treated mice begin to die at 17 weeks and by 6 months all mice are moribund
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• 3 and 6 months, adeno-cre-treated mice exhibit primary lung tumors with metastasis to the liver unlike wild-type mice
• at 3 and 6 month, adeno-cre-treated mice exhibit more tumors than in similarly treated Rb1tm3Tyj Trp53tm1Brn homozygotes
• adeno-cre-treated mice exhibit few lung adenocarcinomas, adenocarcinomas with neuroendocrine features, large-cell neuroendocrine carcinoma, and large-cell carcinomas while most tumors resemble neuroendocrine small-cell lung tumors
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• most tumors in adeno-cre-treated mice resemble those found in human neuroendocrine small cell lung cancer patients
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• 3 and 6 months, adeno-cre-treated mice exhibit primary lung tumors with metastasis to the liver unlike wild-type mice
• at 3 and 6 month, adeno-cre-treated mice exhibit more tumors than in similarly treated Rb1tm3Tyj Trp53tm1Brn homozygotes
• adeno-cre-treated mice exhibit few lung adenocarcinomas, adenocarcinomas with neuroendocrine features, large-cell neuroendocrine carcinoma, and large-cell carcinomas while most tumors resemble neuroendocrine small-cell lung tumors
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• most tumors in adeno-cre-treated mice resemble those found in human neuroendocrine small cell lung cancer patients
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung small cell carcinoma | DOID:5409 |
OMIM:182280 |
J:160148 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adeno-cre-treated mice die by 28 week
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• by 6 months, adeno-cre-treated mice exhibit lung tumors unlike wild-type mice
• adeno-cre-treated mice exhibit few lung adenocarcinomas, adenocarcinomas with neuroendocrine features, large-cell neuroendocrine carcinoma, and large-cell carcinomas while most tumors resemble neuroendocrine small-cell lung tumors
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• most tumors in adeno-cre-treated mice resemble those found in human neuroendocrine small cell lung cancer patients
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• by 6 months, adeno-cre-treated mice exhibit lung tumors unlike wild-type mice
• adeno-cre-treated mice exhibit few lung adenocarcinomas, adenocarcinomas with neuroendocrine features, large-cell neuroendocrine carcinoma, and large-cell carcinomas while most tumors resemble neuroendocrine small-cell lung tumors
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• most tumors in adeno-cre-treated mice resemble those found in human neuroendocrine small cell lung cancer patients
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| lung small cell carcinoma | DOID:5409 |
OMIM:182280 |
J:160148 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants have a median survival of 127 days of age
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• 20.6% of mice show metastatic dissemination, commonly to the lung and liver
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• seen in one mutant
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• mutants develop osteosarcoma with a mean latency of 127 days
• 64.7% of tumors are found in the mandible/head, 11.8% of tumors are found on the lower long bones, and 23.5% of tumors are in other axial locations
• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma
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• mutants develop osteosarcoma with a mean latency of 127 days
• 64.7% of tumors are found in the mandible/head, 11.8% of tumors are found on the lower long bones, and 23.5% of tumors are in other axial locations
• osteosarcoma is characterized by predominant areas of fibroblastic (undifferentiated) morphology accompanied by intermittent areas of mineralized osteoid resembling human fibroblastic/undifferentiated osteosarcoma
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:199542 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice begin to die at ~100 days of age and all die by around 200 days of age, with a median survival similar to that of mutant mice homozygous for the wild-type Prmt1 allele
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• microPET/CT imaging suggested an increase in the presence of osteosarcomas at 100 days of age
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• microPET/CT imaging suggested an increase in the presence of osteosarcomas at 100 days of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median tumor-free survival is significantly increased relative to mutant mice that are either homozygotes for the wild-type Prmt1 allele or heterozygotes with one wild-type and one floxed Prmt1 allele
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• microPET/CT imaging suggested a reduction in the presence of osteosarcomas at 100 days of age
• osteosarcoma tumors retain residual PRMT1 protein expression and a nonexcised Prmt1 allele
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• osteosarcoma initiation is delayed relative to mutant mice that are either homozygotes for the wild-type Prmt1 allele or heterozygotes with one wild-type and one floxed Prmt1 allele
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• microPET/CT imaging suggested a reduction in the presence of osteosarcomas at 100 days of age
• osteosarcoma tumors retain residual PRMT1 protein expression and a nonexcised Prmt1 allele
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice start to die from around 125 days of age, although about 20% survive to 400 days of age
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• tumors show metastasis, most frequently to the lung and then the liver
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• 77.8% penetrance of osteosarcomas with an average latency of 177 days of age
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• 77.8% penetrance of osteosarcomas with an average latency of 177 days of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die from around 125 to 260 days of age
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• tumors show metastasis, most frequently to the lung and then the liver
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• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age
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• develop osteosarcomas at around 4 months of age with 100% penetrance and average latency of 158 days of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:136693 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• overall survival is significantly longer than that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, regardless of whether tumors are located in the jaw or limbs
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• osteosarcoma tumors exhibit a marked increase in mutant p27T187A levels while tumor lysates show elevated CDKN1B (p27) protein levels with similar SKP2 expression relative to tumors from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele
• treatment of early passage tumor cells with CHX (a protein synthesis inhibitor) and MG132 (a proteasome inhibitor) showed enhanced stability of the mutant p27T187A protein, with no significant change in Cdkn1b (p27) mRNA levels
• TUNEL and cleaved caspase-3 immunostaining showed increased apoptosis, while flow cytometry using annexin V/7-AAD staining showed a significant increase in the early
apoptotic population
• primary osteosarcoma tumor cells exhibit less sphere-forming capacity and show reduced stem-like properties (such as ALDH activity) and lower stem-cell frequency and self-renewal ability than tumor cells from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele
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• both limb and jaw osteosarcoma tumors are significantly smaller than those from age-matched mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, indicating delayed tumor progression
• in vivo, tumor growth rate is significantly slower than that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele
• in vitro, primary osteosarcoma cells grown in monolayer cultures proliferate significantly less than tumor cells from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele
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• mice develop osteosarcomas with 100% penetrance at an average of 169 +/- 43.69 days of age
• anatomic distribution of tumors is very similar to that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, including the head and jaw (40.7% versus 42.9%), limbs (39% versus 38.8%), spine and sacrum (10.2% versus 8.2%), and trunk (10.2% versus 10.2%)
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• mice develop osteosarcomas with 100% penetrance at an average of 169 +/- 43.69 days of age
• anatomic distribution of tumors is very similar to that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, including the head and jaw (40.7% versus 42.9%), limbs (39% versus 38.8%), spine and sacrum (10.2% versus 8.2%), and trunk (10.2% versus 10.2%)
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| N |
• mice show no evidence of delayed or stunted growth
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| N |
• mice are fertile
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• about 70% survival at 400 days of age, with some mice starting to die around 150 days of age
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• tumors show metastasis, most frequently to the lung and then the liver
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• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes
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• develop osteosarcomas with a shortened latency (average of 198 days) and increased penetrance (30%) compared to single Trp53 heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age
(J:136693)
• lesions are seen as early as 2 months of age
(J:136693)
• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra
(J:136693)
• tumors exhibit a histology consistent with human medullary osteosarcoma
(J:136693)
• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues
(J:136693)
• metastasis is not seen but this may be due to rapid tumor development
(J:136693)
• mice maintained on doxycycline from conception until 4 weeks of age (preventing gene inactivation until removal of doxycycline), show delayed osteosarcoma development by about 100 days and these mice present with metastatic osteosarcoma but no head tumors
(J:136693)
• mice develop osteosarcomas with 100% penetrance at an average of 154.65 +/- 29.08 days of age
(J:318035)
• anatomic distribution of tumors includes the head and jaw (42.9%), limbs (38.8%), trunk (10.2%) and spine and sacrum (8.2%)
(J:318035)
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• mice begin to die around 95 days of age and all die by 161 days of age
(J:136693)
• mice develop invasive, metastatic osteosarcomas and die within 20-35 weeks of age
(J:318035)
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• slight growth delay that resolves with age
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• mice develop metastatic tumor nodules in the lung
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• about 20% of mice develop adipogenic tumors which occur on the outer chest or abdomen
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• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age
(J:136693)
• lesions are seen as early as 2 months of age
(J:136693)
• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra
(J:136693)
• tumors exhibit a histology consistent with human medullary osteosarcoma
(J:136693)
• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues
(J:136693)
• metastasis is not seen but this may be due to rapid tumor development
(J:136693)
• mice maintained on doxycycline from conception until 4 weeks of age (preventing gene inactivation until removal of doxycycline), show delayed osteosarcoma development by about 100 days and these mice present with metastatic osteosarcoma but no head tumors
(J:136693)
• mice develop osteosarcomas with 100% penetrance at an average of 154.65 +/- 29.08 days of age
(J:318035)
• anatomic distribution of tumors includes the head and jaw (42.9%), limbs (38.8%), trunk (10.2%) and spine and sacrum (8.2%)
(J:318035)
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:136693 , J:318035 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• show completely penetrant osteosarcoma formation between 4 and 8 months of age
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• show completely penetrant osteosarcoma formation between 4 and 8 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx
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• increase in the rate of osteosarcoma initiation compared to mutant mice wild-type for Atrx
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• tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx
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• increase in the rate of osteosarcoma initiation compared to mutant mice wild-type for Atrx
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• tumor formation occurs at an earlier age compared to mutant mice wild-type for Atrx
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in 61% of mice visible unilateral retinoblastoma develop with delayed and variable kinetics appearing on average by 208 +/- 17 days relative to mice lacking Rbl2
• unlike mice lacking Rbl2, bilateral visible retinoblastomas are rare
• however, 3 of 11 retinas from mice with unilateral tumors in the opposite eye contain early retinoblastomas with mitotic figures and Homer-Wright rosettes
• at P60 4 of 14 eyes have retinoblastomas at level of the optic nerve head in the extreme periphery of the retina
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• in 11 of 11 mice with unilateral tumors, the retina in the tumor free eye is disorganized and degenerated
• at P31 6 of 24 retinas have dysplastic lesions containing Homer-Wright rosettes at the level of the optic nerve in the extreme periphery and increased proliferation in the periphery without histological evidence of retinoblastoma
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• in 61% of mice visible unilateral retinoblastoma develop with delayed and variable kinetics appearing on average by 208 +/- 17 days relative to mice lacking Rbl2
• unlike mice lacking Rbl2, bilateral visible retinoblastomas are rare
• however, 3 of 11 retinas from mice with unilateral tumors in the opposite eye contain early retinoblastomas with mitotic figures and Homer-Wright rosettes
• at P60 4 of 14 eyes have retinoblastomas at level of the optic nerve head in the extreme periphery of the retina
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| retinoblastoma | DOID:768 |
OMIM:180200 |
J:119919 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice injected intrasplenicaly with adenovirus expressing Cre recombinase develop multiple liver lesions after a latency of 3-4 months
• tumors resemble human hepatocellular carcinoma
• expansion of populations of stem/progenitor cells suggests that these cells, not hepatocytes, are the initiating populations in hepatocellular carcinoma development
• mutants treated with DAPT, a gamma-secretase inhibitor, 75 days after adenoviral Cre injection, show macroscopically visible tumors 12 days after the beginning of treatment
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• mice injected intrasplenicaly with adenovirus expressing Cre recombinase develop multiple liver lesions after a latency of 3-4 months
• tumors resemble human hepatocellular carcinoma
• expansion of populations of stem/progenitor cells suggests that these cells, not hepatocytes, are the initiating populations in hepatocellular carcinoma development
• mutants treated with DAPT, a gamma-secretase inhibitor, 75 days after adenoviral Cre injection, show macroscopically visible tumors 12 days after the beginning of treatment
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:177573 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt die prior to weaning
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• mice exhibit higher apoptosis levels than in wild-type and Rb1tm3Tyj/Rb1tm3Tyj Tg(Nes-cre)1Mrt mice
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• at E18.5, massive retinal dysplasia is evident
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• mice exhibit higher apoptosis levels than in wild-type and Rb1tm3Tyj/Rb1tm3Tyj Tg(Nes-cre)1Mrt mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit an average lifespan of 92+/-15 days and are moribund with pituitary tumors when euthanized
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• mice with mosaic cre expression with maternal inheritance of Tg(Nes-cre)1Mrt exhibit pituitary tumors
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• retinal apoptosis levels are higher than in wild-type and Rb1tm3Tyj/Rb1tm3Tyj Tg(Nes-cre)1Mrt mice
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• dysplasia in both eyes
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit focal retinal dysplasia
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• in mice with mosaic cre expression when Tg(Nes-cre)1Mrt is maternally inherited
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• mice with mosaic cre expression with maternal inheritance of Tg(Nes-cre)1Mrt exhibit pituitary tumors
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• mice with mosaic cre expression with maternal inheritance of Tg(Nes-cre)1Mrt exhibit pituitary tumors
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• retinal apoptosis levels are higher than in wild-type and Rb1tm3Tyj/Rb1tm3Tyj Tg(Nes-cre)1Mrt mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit an average tumor-free lifespan of 97 days but where sacrificed when moribund
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• apoptosis levels are higher than in wild-type mice but not higher than in Rb1tm3Tyj/Rb1tm3Tyj Tg(Nes-cre)1Mrt mice
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit bilateral retinoblastomas that invade surrounding muscle, exhibit rosettes, have foci with high levels of apoptosis and mitoses and are of amacrine lineage
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit bilateral retinoblastomas that invade surrounding muscle, exhibit rosettes, have foci with high levels of apoptosis and mitoses and are of amacrine lineage
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• fewer than expected mice are produced with maternal inheritance of Tg(Nes-cre)1Mrt
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• apoptosis levels are higher than in wild-type mice but not higher than in Rb1tm3Tyj/Rb1tm3Tyj Tg(Nes-cre)1Mrt mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| retinoblastoma | DOID:768 |
OMIM:180200 |
J:91406 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• extensive at P4 and P12
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• ectopic S-phase and mitotic activity are detected unlike in wild-type mice throughout the entire retina
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• at E18.5, in the retinal ganglion cell layer
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• some inner cell layer cells are very large and of horizontal cell lineage
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• disorganized
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• at E18.5, in the retinal ganglion cell layer
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• extensive at P4 and P12
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• median life span of cre adenovirus-treated mice is 20 weeks
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• tumors from cre adenovirus-treated mice exhibit lower cell proliferation rates compared to in tumors from Krastm4Tyj heterozygotes
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• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas, and bronchiolar hyperplasia and dysplasia
• at end stage, 25% of cre adenovirus-treated mice develop grade 5 tumors, defined by stromal desmoplasia
• cre adenovirus-treated mice develop more numerous tumors than in cre adenovirus-treated Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
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• in cre adenovirus-treated mice
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• mice treated with adenovirus cre develop lung lesions in 4 to 6 months
• cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas, and bronchiolar hyperplasia and dysplasia
• at end stage, 25% of cre adenovirus-treated mice develop grade 5 tumors, defined by stromal desmoplasia
• cre adenovirus-treated mice develop more numerous tumors than in cre adenovirus-treated Krastm4Tyj heterozygotes and Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice
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• in cre adenovirus-treated mice
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• cre adenovirus-treated mice develop bronchiolar hyperplasia and dysplasia unlike wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice are moribund by 183 +/- 39 days
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• visible bilateral retinoblastoma develop with rapid and consistent kinetics appearing on average at 128 +/- 18 days
• amacrine cells, a subset of progenitor cells, and Muller cells are present in tumors
• at P31 (4 animals) and P60 (3 animals) large tumors are present and all mice have retinoblastomas in each eye that seed the vitreous and anterior chamber by 4 months of age
• by 183 +/- 39 days mice have grossly distended eyes where the tumor has filled the anterior chambers and often invaded of local tissues
• tumors infiltrate the optic nerve and metastases are found in the cervical lymph nodes (11 of 28) and brain (7 of 27)
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• at P12, apoptosis is increased and at P21 retinas contain apoptotic bodies
• the increase in apoptosis is greater than in mutant mice wild-type for Rbl2
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• at P12 in the retinal periphery proliferation and apoptosis are increased and proliferation remains elevated at P21,especially in the extreme periphery
• proliferation is increased and prolonged relative to mutant mice wild-type for Rbl2
• at P21 retinas are very hypocellular, contain apoptotic bodies and many cells with large and/or irregular-shaped nuclei, and 9 of 12 have early dysplatic lesions containing Homer-Wright rosettes in the extreme periphery
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• visible bilateral retinoblastoma develop with rapid and consistent kinetics appearing on average at 128 +/- 18 days
• amacrine cells, a subset of progenitor cells, and Muller cells are present in tumors
• at P31 (4 animals) and P60 (3 animals) large tumors are present and all mice have retinoblastomas in each eye that seed the vitreous and anterior chamber by 4 months of age
• by 183 +/- 39 days mice have grossly distended eyes where the tumor has filled the anterior chambers and often invaded of local tissues
• tumors infiltrate the optic nerve and metastases are found in the cervical lymph nodes (11 of 28) and brain (7 of 27)
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• at P21, the amacrine layer is significantly reduced away from tumor areas
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• rod bipolar cells are very rare or absent from retinas and retinoblastomas
|
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• increase in horizontal cells in contrast to the general hypocellularity of the retina
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• at P21, the three nuclear layers can not be distinguished, except in the central retina where Cre expression is reduced
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• Tuji-positive retinal ganglion cells are very rare or completely absent from retinas and tumors
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• a cone subset (positive for M-opsin) is very rare or absent from retinas and retinoblastomas
|
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• despite the increase in proliferation retinas are very hypoplastic at P21
|
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• Tuji-positive retinal ganglion cells are very rare or completely absent from retinas and tumors
|
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• a cone subset (positive for M-opsin) is very rare or absent from retinas and retinoblastomas
|
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• at P21, the amacrine layer is significantly reduced away from tumor areas
|
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• rod bipolar cells are very rare or absent from retinas and retinoblastomas
|
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• increase in horizontal cells in contrast to the general hypocellularity of the retina
|
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• at P12, apoptosis is increased and at P21 retinas contain apoptotic bodies
• the increase in apoptosis is greater than in mutant mice wild-type for Rbl2
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| retinoblastoma | DOID:768 |
OMIM:180200 |
J:119919 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased apoptosis is seen
|
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• at P12 extensive cell proliferation occurs
• however, by P21 proliferation is no longer detected unlike in mice that also lack Rbl2
|
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• increased apoptosis is seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
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• testes of mature males are small relative to controls
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• testis weight increases similar to controls in initial 3-4 weeks of age, then begins to decline and remains low in adult males
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• when males are housed with wild-type females for 21 weeks from 4 weeks of age, each animal only sires one litter (litter is slightly decreased in size versus wild-type males); control males sire 4-6 litters over 21 week period
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• by 2 months of age, males are sterile
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• testes of mature males are small relative to controls
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• testis weight increases similar to controls in initial 3-4 weeks of age, then begins to decline and remains low in adult males
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants have a median survival of 401 days
|
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• 85.72% of mice show metastatic dissemination, commonly to the lung and liver
• high degrees of mineralization are apparent in primary and metastatic lesions
|
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• mutants develop osteosarcoma with a mean latency of 401 days
• 42.9% of tumors are found on the lower long bones, 42.9% of tumors are found on the mandible/head, and 14.3% of tumors are in other axial locations
• osteosarcoma is characterized by a uniform heavily mineralized osteoblastic (well differentiated) appearance in both primary and metastatic sites and osteosarcomas fail to become adipogenic under inductive conditions, indicating a cell population that is osteoblast restricted
• tumors resemble human osteoblastic osteosarcoma
• osteosarcomas exhibit clonal cytogenic abnormalities and karyotypic complexity; most frequent changes are recurrent gains of chromosomes 14 and 15 and loss of chromosomes 3, 7, and 12, as well as inter-chromosomal rearrangement involving chromosomes 6, 8, and 15
• however, nonosteoblastic lineage sarcomas or hibernomas are not seen in mutants
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• increase in serum alkaline phosphatase levels
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• mutants develop osteosarcoma with a mean latency of 401 days
• 42.9% of tumors are found on the lower long bones, 42.9% of tumors are found on the mandible/head, and 14.3% of tumors are in other axial locations
• osteosarcoma is characterized by a uniform heavily mineralized osteoblastic (well differentiated) appearance in both primary and metastatic sites and osteosarcomas fail to become adipogenic under inductive conditions, indicating a cell population that is osteoblast restricted
• tumors resemble human osteoblastic osteosarcoma
• osteosarcomas exhibit clonal cytogenic abnormalities and karyotypic complexity; most frequent changes are recurrent gains of chromosomes 14 and 15 and loss of chromosomes 3, 7, and 12, as well as inter-chromosomal rearrangement involving chromosomes 6, 8, and 15
• however, nonosteoblastic lineage sarcomas or hibernomas are not seen in mutants
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:199542 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thickness of the granular layer is increased
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• thickness of the spinous suprabasal layer is increased
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thickness of the granular layer is increased to a greater extent than in conditional RB1 mice that lack Tg(KRT14-HPV16E7)2304Plam
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• thickness of the spinous suprabasal layer is increased
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• epidermal hyperplasia is increased compared to conditional RB1 mice that lack Tg(KRT14-HPV16E7)2304Plam
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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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• mutants die within 30 minutes of birth
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• at E13.5, apoptosis is increased in the dorsal root ganglia and trigeminal ganglia, but not in the brain
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• at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia
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• at E18.5, mutant brains are visibly larger than controls
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• at E18.5, mutant brains weigh 27% more than controls and no signs of hydrocephalus are seen
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• at E13.5 and E18.5, ectopic proliferating cells are seen in the interior of the lens and increased apoptosis is seen
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• seen at E18.5
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• at E18.5 skeletal muscle differentiation is impaired, abnormally large nuclei with inappropriate S-phase activity are present, and myotubes appear diffusely arranged
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| N |
• at E13.5 peripheral blood smears contain the normal mix of nucleated and enucleated erythrocytes
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| N |
• at E13.5, liver cellularity and level of apoptosis are normal
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• at E13.5, apoptosis is increased in the dorsal root ganglia and trigeminal ganglia, but not in the brain
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• at E13.5, proliferation is increased in the brain, dorsal root ganglia, and trigeminal ganglia
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit an average lifespan of 107 days and are moribund with pituitary tumors when euthanized
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit pituitary tumors
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• mice exhibit increased apoptosis in the retina, especially in the retinal ganglion cell layer compared to wild-type mice
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• in mice with mosaic cre expression when Tg(Nes-cre)1Mrt is maternally inherited
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• cell within the inner nuclear cell layer exhibit subtle defects in mice with mosaic cre expression when Tg(Nes-cre)1Mrt is maternally inherited
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit retinal inner nuclear layer disorganization with clusters of ectopic inner nuclear layer cells in the outer plexiform layers approaching the photoreceptors
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• in mice with mosaic cre expression when Tg(Nes-cre)1Mrt is maternally inherited
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit pituitary tumors
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• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt exhibit pituitary tumors
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• in mice with mosaic cre expression when Tg(Nes-cre)1Mrt is maternally inherited
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• fewer than expected mice are produced with maternal inheritance of Tg(Nes-cre)1Mrt
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• mice exhibit increased apoptosis in the retina, especially in the retinal ganglion cell layer compared to wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Increase in ploidy in hepatocytes of tamoxifen-treated Rb1tm3Tyj/Rb1tm3Tyj Tg(tetO-MYC)36aBop/0 Tg(Cebpb-tTA)5Bjd/0 mice
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• median survival of mutants is 27 weeks following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase
• median survival of mutants with tumors is 16.5 weeks following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase
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• following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase, some mice develop liver tumors composed of multiple fleshy vascular nodules
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• tumors of mice injected with adenovirus expressing Cre recombinase and without doxycycline to induce MYC expression are composed of hepatocellular neoplasms characterized by sheets of cells with occasional mitotic figure, slightly pleomorphic nuclei, and prominent nucleoli
• tumors show a range of differentiation between well- and moderately-differentiated hepatocellular carcinoma
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• following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase, adult liver cells exhibit an increase in polyploidy
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• following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase, some mice develop liver tumors composed of multiple fleshy vascular nodules
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• tumors of mice injected with adenovirus expressing Cre recombinase and without doxycycline to induce MYC expression are composed of hepatocellular neoplasms characterized by sheets of cells with occasional mitotic figure, slightly pleomorphic nuclei, and prominent nucleoli
• tumors show a range of differentiation between well- and moderately-differentiated hepatocellular carcinoma
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:172430 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thickness of the granular layer is increased to a greater extent than in conditional RB1 mice that lack Tg(KRT14-HPV16E7)2304Plam
|
|
• thickness of the spinous suprabasal layer is increased
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 12/10/2024 MGI 6.24 |
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