B6.129S2-Trp53^tm1Tyj/J

Stock number: 002101
Product name: p53 KO
Research areas: Apoptosis Research, Cancer Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Research Tools

Description

Trp53 knockout mutant mice develop tumors at three to six months of age. They are suitable for use in applications related to the study of familial breast cancers such as Li-Fraumeni syndrome as well as research of lung, brain and bone tumors, lymphoma and leukemia, and other rare cancers.

Detailed description

A neomycin cassette replaces exons 2-6 (including the start codon) of the transformation related protein 53 gene (Trp53). Mice homozygous for the mutation show no visible phenotype but most develop tumors (principally lymphomas and sarcomas) at three to six months of age. Heterozygous mice develop tumors at about 10 months of age. These mice model some of the features of human Li-Fraumeni syndrome, a form of familial breast cancer with mutations in TRP53. Homozygous mice may produce a litter before succumbing to tumors.

For the C57BL/6-J congenic Trp53^tm1Tyj mouse line (Stock No. 002101), it is the experience of The Jackson Laboratory that homozygous males have expected Mendelian survival rates at wean age, but homozygous females have significantly reduced survival by wean age. Specifically, breeding heterozygous females to heterozygous males results in only ~3.5% homozygous females by wean age (expected Mendelian 12.5%). Additionally, breeding heterozygous females to homozygous males results in only ~6.8% homozygous females by wean age (expected Mendelian 25%).

Development

The Trp53^tm1Tyj mutant strain was developed in the laboratory of Dr. Tyler Jacks at the Center for Cancer Research at the Massachusetts Institute of Technology. The 129-derived D3 ES cell line was used. The C57BL/6J strain was produced by backcrossing the Trp53^tm1Tyj mutation at least five times to C57BL/6J inbred mice.



A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 43 markers, on Chromosome 8, was segregating with 129.

Allele

Symbol: Trp53^tm1Tyj
Name: targeted mutation 1, Tyler Jacks
MGI accession ID: MGI:1857263
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Trp53
Marker name: transformation related protein 53
Chromosome: 11
Strain of origin: 129S2/SvPas
Site of expression: Normal Trp53 expression is widespread.
Molecular note: A neomycin cassette replaced 40% of the coding sequences beginning with exon 2 (upstream of the translation start site) and extending into exon 6.
General note: This mutant allele was produced by a targeted neo insertion into the Trp53 locus. Homozygotes show no visible phenotype but develop tumors at 3-6 months of age. Heterozygotes develop tumors at 10 months of age. These mice model some of the features of human Li-Fraumeni syndrome (OMIM 151623), a form of familial breast cancer with mutations in TRP53 (J:16022)(J:16023) A specific human mutation found in hepatocellular carcinomas caused by hepatitis B infection or by aflatoxin exposure has been created in a mouse model, resulting in a similar gene product (J:27363).