Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-RNAi:Trp53)ASlowe
• Allele Name: transgene insertion A, Scott W Lowe
• Allele ID: MGI:5521542
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Rb1^tm3Tyj/Rb1^tm3Tyj Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0 Tg(tetO-RNAi:Trp53)ASlowe/0	involves: 129S4/SvJae * C57BL/6 * CD-1	MGI:5521547
cx2	Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0 Tg(tetO-RNAi:Trp53)ASlowe/0	involves: C57BL/6 * CD-1	MGI:5521546
cx3	Tg(EmuSR-tTa)83Bop/0 Tg(IghMyc)22Bri/0 Tg(tetO-RNAi:Trp53)ASlowe/0	involves: C57BL * C57BL/6 * FVB/N * SJL	MGI:5521543

Genotype
MGI:5521547

cn1

• 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

Genotype
MGI:5521546

cx2

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

mortality/aging

premature death ( J:199542 )

• median survival is 485 days of age

neoplasm

increased metastatic potential ( J:199542 )

• 83.3% of mice show metastatic dissemination, commonly to the lung and liver

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 485 days

• 66.7% of tumors are in the long bones, 16.7% of tumors are found in the mandible/head, and 16.7% 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

skeleton

increased osteosarcoma incidence ( J:199542 )

• mutants develop osteosarcoma with a mean latency of 485 days

• 66.7% of tumors are in the long bones, 16.7% of tumors are found in the mandible/head, and 16.7% 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

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

Genotype
MGI:5521543

cx3

• Allelic Composition: Tg(EmuSR-tTa)83Bop/0; Tg(IghMyc)22Bri/0; Tg(tetO-RNAi:Trp53)ASlowe/0
• Genetic Background: involves: C57BL * C57BL/6 * FVB/N * SJL

mortality/aging

decreased tumor-free survival time ( J:123006 )

• mutants become moribund without a large peripheral tumor burden, with a median survival of 82 days

neoplasm

increased lymphoma incidence ( J:123006 )

• mutants develop lymphoma, with latency of tumorigenesis reduced compared to single Tg(IghMyc)22Bri/0 mice

• lymphoma-bearing mice treated with doxycycline at the onset of paralysis regain full movement within 2 days of doxycycline treatment, show tumor involution, and live for a further 24-64 days before tumors relapse

growth/size/body

enlarged spleen ( J:123006 )

• spleen is enlarged and taken over by B220+ IgM- (pre-B) tumor cells, with lymphoma dissemination into the lymph nodes and liver

hematopoietic system

enlarged spleen ( J:123006 )

• spleen is enlarged and taken over by B220+ IgM- (pre-B) tumor cells, with lymphoma dissemination into the lymph nodes and liver

immune system

enlarged spleen ( J:123006 )

• spleen is enlarged and taken over by B220+ IgM- (pre-B) tumor cells, with lymphoma dissemination into the lymph nodes and liver

behavior/neurological

hindlimb paralysis ( J:123006 )

• partial hind leg paralysis is seen in some mutants, most likely attributed to lymphoma