Phenotypes Associated with This Genotype

Genotype
MGI:5519094

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

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

skeleton

increased osteosarcoma incidence ( J:136693 , J:318035 )

• metastasis is not seen but this may be due to rapid tumor development (J:136693)

• 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)

• 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)

mortality/aging

premature death ( J:136693 , J:318035 )

• mice begin to die around 95 days of age and all die by 161 days of age (J:136693)

• mice develop invasive, metastatic osteosarcomas and die within 20-35 weeks of age (J:318035)

growth/size/body

postnatal growth retardation ( J:136693 )

• slight growth delay that resolves with age

neoplasm

increased metastatic potential ( J:318035 )

• mice develop metastatic tumor nodules in the lung

increased tumor incidence ( J:136693 )

• about 20% of mice develop adipogenic tumors which occur on the outer chest or abdomen

increased osteosarcoma incidence ( J:136693 , J:318035 )

• mice develop osteosarcomas at around 4 months of age with 100% penetrance and an average latency of 128 days of age (J:136693)

• lesions are seen as early as 2 months of age (J:136693)

• most frequent site of osteosarcomas is the jaw and head, followed by the hind leg/hip and ribs and vertebra (J:136693)

• tumors exhibit a histology consistent with human medullary osteosarcoma (J:136693)

• distribution of osteosarcoma is typically metaphyseal, with growth into the central medullary cavity and with extraosseous extension into the soft tissues (J:136693)

• metastasis is not seen but this may be due to rapid tumor development (J:136693)

• mice maintained on doxycycline from conception until 4 weeks of age (preventing gene inactivation until removal of doxycycline), show delayed osteosarcoma development by about 100 days and these mice present with metastatic osteosarcoma but no head tumors (J:136693)

• mice develop osteosarcomas with 100% penetrance at an average of 154.65 +/- 29.08 days of age (J:318035)

• anatomic distribution of tumors includes the head and jaw (42.9%), limbs (38.8%), trunk (10.2%) and spine and sacrum (8.2%) (J:318035)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteosarcoma		DOID:3347	OMIM:259500	J:136693 , J:318035