Phenotypes Associated with This Genotype

Genotype
MGI:5521547

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0; Tg(tetO-RNAi:Trp53)ASlowe/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:199542 )

• mutants have a median survival of 401 days

neoplasm

increased metastatic potential ( J:199542 )

• 85.72% of mice show metastatic dissemination, commonly to the lung and liver

• high degrees of mineralization are apparent in primary and metastatic lesions

increased osteosarcoma incidence ( J:199542 )

• 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

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:199542 )

• increase in serum alkaline phosphatase levels

skeleton

increased osteosarcoma incidence ( J:199542 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:199542