Analysis Tools
reproductive system
infertility
(
J:98799
)
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• after 3 to 4 generations of inbreeding to C3H or to A/J
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Allele Symbol Allele Name Allele ID |
Prkar1a+ wild type MGI:2433330 |
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| Summary |
12 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after 3 to 4 generations of inbreeding to C3H or to A/J
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• commonly found on proximal hind limb but elsewhere as well
• interlacing bundles of parallel spindle cells with large eosinophilic cytoplasmic granules
• look like hypertrophic Schwann cells - Schwannomas
• no melanotic pigmentation
• tail tumors as well starting around 5 to 6 months
• bone loss in individual vertebrae of the tail
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• epithelial thyroid cancer
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• epithelial thyroid cancer
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Carney complex | DOID:0050471 |
OMIM:160980 OMIM:605244 OMIM:608837 |
J:98799 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• heterozygotes develop bone lesions derived from camp-responsive osteogenic cells and resemble fibrous dysplasia
• about 50% of mutants develop osteomyoxomas in the caudal vertebrae by 8 months of age, with 100% of mice showing these by one year
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• rare development of metastatic osteochondrosarcomas
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• overall bone mineralization density is lower than in wild-type mice
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• heterozygotes develop bone lesions derived from camp-responsive osteogenic cells and resemble fibrous dysplasia
• about 50% of mutants develop osteomyoxomas in the caudal vertebrae by 8 months of age, with 100% of mice showing these by one year
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• rare development of metastatic osteochondrosarcomas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Carney complex | DOID:0050471 |
OMIM:160980 OMIM:605244 OMIM:608837 |
J:160299 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Tumors in Prkar1atm1Gsm/Prkar1a+ mice
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• depressed heart rate variability, however exhibit no heart rate changes, conduction delay or any cardiac myxomas
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• 5 of 12 mutants that develop tumors have hepatocellular carcinomas
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• increase in frequency of extracardiac tumors; 12 of 17 mutants developed tumors
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• 5 of 12 mutants that develop tumors have hepatocellular carcinomas
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• 3 of 12 mutants that develop tumors have soft tissue sarcomas with myxomatous differentiation invading the calvaria
• 2 of 12 mutants that develop tumors have paraspinal and spinal sarcomas (chondro- and meningeal saracomas) with cord compression and lower limb paralysis
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• 2 of 12 mutants that develop tumors have s.c. soft tissue myxoid fibrosarcomas of the forelimb
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• 4 of 12 mutants that develop tumors have hemangiosarcomas of the spleen with myxoid regions
• splenic hemangiosarcomas are associated with metachronous lesions including colonic, ovarian, and pulmonary hemangiosarcomas
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| N |
• pigmentation is normal
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Carney complex | DOID:0050471 |
OMIM:160980 OMIM:605244 OMIM:608837 |
J:93393 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no litters are obtained when heterozygous females are bred with either wild-type mice or heterozygous males
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• mice exhibit slightly shorter and blunt snouts
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• plasma parathyroid hormone levels are increased
• however, mice exhibit normal thyroid stimulating hormone levels and normal plasma calcium and phosphorus concentrations
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• basal urinary cAMP levels are increased
• however, urine/calcium/creatinine clearance ratio and urinary phosphorus normalized by urinary creatinine are normal in males
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• shorter cranial and skull bone lengths
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• shortening of the diaphysis of endochondral bone at P4
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• shortening of the metaphysis of endochondral bone at P4
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• skeletal bone mineral density is decreased at P4
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• bone volume and bone surface are decreased
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• tibia is smaller and appears to have reduced formation of primary spongiosa and trabecular bone, suggesting a defect in bone mineralization
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• mice exhibit peripheral acrodysostosis affecting the endochondral skeleton as indicated by short stature, short tail, and short forelimbs and hindlimbs
• however, joint formation is normal
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• growth plate shows more diffuse and columnar PCNA+ cells which are also present in the zone in proximity of the cartilage/bone junction
• the number of PCNA+ cells per prehypertrophic/hypertrophic chondrocyte column is increased
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• increase in the height of the columnar proliferative prehypertrophic chondrocyte layer
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• decrease in the height of the hypertrophic chondrocyte layer
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• delay in mineralization of the cartilage and epiphyseal secondary ossification centers is seen in forelimb and hindlimb bones indicating a delay in endochondral bone development
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• facial dysostosis as indicated by shorter cranial and skull bone lengths and foramen magnum diameters
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• shorter cranial and skull bone lengths
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• mice exhibit slightly shorter and blunt snouts
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• mice exhibit shorter digits affecting both forelimbs and hindlimbs
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• mice exhibit shorter forelimbs and hindlimbs
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• basal urinary cAMP levels are increased
• however, urine/calcium/creatinine clearance ratio and urinary phosphorus normalized by urinary creatinine are normal in males
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| acrodysostosis | DOID:14669 |
OMIM:101800 OMIM:614613 |
J:303060 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice do not live longer than 11 weeks
• treatment of mice with RANK-Fc prolongs survival to around to around 13.3 weeks
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• mice develop osteosarcoma within 6.3 weeks of age
• tumors are marked by high (TNFSF11) RANKL/low (TNFRSF11A) RANK levels
• treatment of mice with RANK-Fc starting at 2.4 weeks of age suppresses tumor growth
• mice develop tumors 4.3 weeks after the discontinuation of RANK-Fc treatment and large numbers of osteoclasts are seen lining the boundary of tumor cells and adjacent osteopetrotic bone
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• mice develop osteosarcoma within 6.3 weeks of age
• tumors are marked by high (TNFSF11) RANKL/low (TNFRSF11A) RANK levels
• treatment of mice with RANK-Fc starting at 2.4 weeks of age suppresses tumor growth
• mice develop tumors 4.3 weeks after the discontinuation of RANK-Fc treatment and large numbers of osteoclasts are seen lining the boundary of tumor cells and adjacent osteopetrotic bone
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:234128 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice survive to around 13.9 weeks
• treatment of mice with RANK-Fc prolongs survival to around 17.8 weeks
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• mice develop osteosarcoma within 10.3 weeks of age
• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels
• treatment of mice with RANK-Fc for 52 weeks beginning at 12.6 weeks of age keeps mice tumor-free until 64.6 weeks of age
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• mice develop osteosarcoma within 10.3 weeks of age
• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels
• treatment of mice with RANK-Fc for 52 weeks beginning at 12.6 weeks of age keeps mice tumor-free until 64.6 weeks of age
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• in a scratch wound healing assay, tumor cells show greater migration than tumor cells from conditional Rb1tm2Brn heterozygous Trp53tm1Brn homozygous double mutants
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:234128 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice survive to around 17 weeks of age
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• mice develop osteosarcoma within 17 weeks of age
• multiple tumors among long bones, spine, jaw, and skull
• tumors are composed of malignant-appearing osteoblasts with woven bone as the predominant matrix and occasional chondroblastic or fibroblastic phenotype
• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels
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• mice develop osteosarcoma within 17 weeks of age
• multiple tumors among long bones, spine, jaw, and skull
• tumors are composed of malignant-appearing osteoblasts with woven bone as the predominant matrix and occasional chondroblastic or fibroblastic phenotype
• tumors are marked by high TNFSF11 (RANKL)/low TNFRSF11A (RANK) levels
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteosarcoma | DOID:3347 |
OMIM:259500 |
J:234128 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Prkar1a heterozygosity accelerates osteosarcoma development in Tg(Bglap2-TAg)1Rkho/0 mice
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• no mice survive past 5 weeks of age
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• mice develop advanced osteosarcoma, often in the spine
• mice exhibit multi-ostotic tumors in long and flat bones, including the skull, vertebrae, ribs, and tibia
• however, metastasis is not seen at this early age
• tumors show increased osteoclast numbers
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• mice develop advanced osteosarcoma, often in the spine
• mice exhibit multi-ostotic tumors in long and flat bones, including the skull, vertebrae, ribs, and tibia
• however, metastasis is not seen at this early age
• tumors show increased osteoclast numbers
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• impaired mobility due to osteosarcoma in the spine
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Bone tumorigenesis nd abundant osteoclasts in Prkar1atm1.2Lsk/Prkar1a+ Tg(Col1a1-cre)1Kry/0 mice
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• mice develop bone tumors starting at 10 weeks of age, with most mice having tumors by 40 weeks of age
• lesions grow slowly, with 25% of mice having 8-mm tumors by 50 weeks of age
• mice do not develop metastases
• lesions are not typical osteosarcomas as they are not composed of malignant osteoblasts depositing osteoid, but consist of an enlarged marrow space filled with abundant myxoid matrix, containing small fibroblast-like cells surrounded by trabecular-like bone, lined by normal osteoblasts and regions with abundant osteoclasts
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• mice develop bone tumors starting at 10 weeks of age, with most mice having tumors by 40 weeks of age
• lesions grow slowly, with 25% of mice having 8-mm tumors by 50 weeks of age
• mice do not develop metastases
• lesions are not typical osteosarcomas as they are not composed of malignant osteoblasts depositing osteoid, but consist of an enlarged marrow space filled with abundant myxoid matrix, containing small fibroblast-like cells surrounded by trabecular-like bone, lined by normal osteoblasts and regions with abundant osteoclasts
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• bone within and around lesions is normal and contains osteocytes but is undergoing extensive remodeling
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit reduced survival compared to single heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants develop a greater number of osseous lesions and develop them earlier than single Prkar1a heterozygotes
(J:160299)
• 90% of mutants exhibit bone lesions in the tail by 6 months and 100% by 9 months of age
(J:160299)
• osseous lesions are seen starting around 3 months of age and vary from rare chondromas in the long bones and ubiquitous osteochondrodysplasia of vertebral bodies to occasional sarcoma
(J:160299)
• 13% of mutants develop osteochondromyoxoma
(J:160299)
• cells from the bone lesions originate from an area proximal to the growth plate
(J:160299)
• cartilaginous metaplasia, chondromas, and osteochondrodysplasia are seen in marrow cavities of up to 1/3 of the long bones and most of the vertebral bodies
(J:160299)
• lesions are hypercellular and contain more irregular cartilage or bone islands; proliferating cells are committed osteogenic but are not able to mature into osteoblasts
(J:160299)
• mutants develop bone tumors with histological resemblance to those seen in humans with neonatal-onset multisystem inflammatory disease, with lesions derived from osteoblast progenitor cells
(J:166728)
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• rare development of metastatic osteochondrosarcomas
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• rare chondromas in the long bones
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• mutants develop a greater number of osseous lesions and develop them earlier than single Prkar1a heterozygotes
(J:160299)
• 90% of mutants exhibit bone lesions in the tail by 6 months and 100% by 9 months of age
(J:160299)
• osseous lesions are seen starting around 3 months of age and vary from rare chondromas in the long bones and ubiquitous osteochondrodysplasia of vertebral bodies to occasional sarcoma
(J:160299)
• 13% of mutants develop osteochondromyoxoma
(J:160299)
• cells from the bone lesions originate from an area proximal to the growth plate
(J:160299)
• cartilaginous metaplasia, chondromas, and osteochondrodysplasia are seen in marrow cavities of up to 1/3 of the long bones and most of the vertebral bodies
(J:160299)
• lesions are hypercellular and contain more irregular cartilage or bone islands; proliferating cells are committed osteogenic but are not able to mature into osteoblasts
(J:160299)
• mutants develop bone tumors with histological resemblance to those seen in humans with neonatal-onset multisystem inflammatory disease, with lesions derived from osteoblast progenitor cells
(J:166728)
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• rare development of metastatic osteochondrosarcomas
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• rare chondromas in the long bones
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• overall bone mineralization density is lower than in wild-type mice
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• in affected bones, normal cortical bone is replaced by mineralized material
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• periosteum of affected bones is abnormal, with occasional cells from lesions crossing the periosteum into the extraosseous space and Sharpey fibers, characteristic of fibrous dysplasia, are observed
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• although the bone marrow is expanded by active osteoclastic activity, these cells are not able to mature into osteoblasts and mineralize the matrix resulting in undermineralization
• bones exhibit a lag between bone matrix formation and mineralization and abnormal coordination of these processes with bone resorption
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| CINCA Syndrome | DOID:0090029 |
OMIM:607115 |
J:166728 | |
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 06/12/2024 MGI 6.13 |
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