SJL/J-Trp53^em2Mvw/J

Stock number: 033940
Product name: TRP53 null
Strain synonyms: Trp53 Δ176, Trp53 KO

Research areas: Cancer Research, Mouse/Human Gene Homologs

Description

Trp53 Δ176 mice lack exon 4 of the transformation related protein 53 gene (Trp53). On the SJL/J background, these Trp53 knock-out mice rapidly develop thymic lymphomas, testicular teratomas, and rhabdomyosarcomas (average onset ~11 weeks of age). These mice may be useful in the study of oncology and tumorigenesis.

Detailed description

Transformation-related protein 53 (Trp53) encodes a well-known tumor suppressor protein which is involved in transcriptional regulation, DNA repair, autophagy, and apoptosis. These CRISPR-generated Trp53 Δ176 knock-out mice carry a 176 bp deletion in exon 4, which results in a null allele on the SJL/J genetic background. Similar to Trp53 knock-out alleles on other backgrounds (for example, Stock No. 002101), mice homozygous for the Trp53 Δ176 knock-out allele are prone to the development of thymic lymphomas and testicular teratomas. However, in comparison to other Trp53 knock-outs, tumor progression is more rapid and severe on the SJL/J background, with 50% mortality at 12 weeks of age among homozygotes, and 100% mortality by 35 weeks, with 80% of animals showing visible tumors. Heterozygotes express a hypomorphic phenotype, with a greater incidence of rhabdomyosarcomas, and ~70% survival at 35 weeks of age. This strain may be useful for rapid and efficient study of tumorigenesis and therapeutic screening.

Development

This Trp53^em2Mvw mutant strain was developed in the laboratory of Muneer Hasham at The Jackson Laboratory. Briefly, two truncated single guide RNAs (TRU-sgRNAs) were designed to target exon 4 of the endogenous Trp53 gene and injected into SJL/J zygotes along with cas9 mRNA. Embryos were then transferred to pseudopregnant recipient females and the pups were subsequently screened by PCR and Sanger sequencing. Sequencing revealed a 176 bp deletion in the targeted region (Δ176). Selected founders were then backcrossed to SJL/J mice for germline transmission. In 2020, the strain was donated to The Jackson Laboratory, at which time sperm was frozen. To establish our live colony, an aliquot of frozen sperm was used to fertilize SJL/J oocytes (Stock No. 000686).

Allele

Symbol: Trp53^em2Mvw
Name: endonuclease-mediated mutation 2, Michael Wiles
MGI accession ID: MGI:6199168
Generation method: Endonuclease-mediated
Attributes: Null/Knockout
Synonyms: Trp53 delta176
Marker symbol: Trp53
Marker name: transformation related protein 53
Marker synonyms: BCC7; BMFS5; LFS1; p44; p53; TRP53
Chromosome: 11
Strain of origin: SJL/J
Molecular note: Microinjection of CRISPR/Cas9 and guide sequences into fertilized oocytes yielded this 176 base pair deletion, which begins in the early part of exon 4 (GAGTGCAGGAGCTCCT), eliminates nearly the entire exon, and is predicted to cause a frameshift.