B6.129S1-Ing1^tm1Avg/J

Stock number: 007263
Product name: Ing1 KO
Research areas: Cancer Research

Description

Homozygous knockout mutants exhibit increased mortality induced by gamma-irradiation, increased B cell derived lymphoma incidence, splenomegaly, and premature death.

Detailed description

Mice homozygous for the targeted mutation are viable, fertile, and do not display any gross physical or behavioral abnormalities. Homozygotes are smaller than their wildtype littermates. Homozygous births from heterozygous crosses occur at a lower than expected frequency. During a 23 month period homozygotes exhibit increased morbidity or visible abnormalities including splenomegaly and an increased incidence of lymphomas (follicular center B-cell lymphomas) when compared to wild type littermates. When exposed to 6 consecutive daily doses of 2.34Gy total body gamma irradiation, mutant mice have a lower survival rate than wildtype controls. Mouse embryonic fibroblasts (MEFs) from homozygous animals are slightly more sensitive to UV-B exposure. This mutant mouse strain may be useful in studies of hypersensitivity to gamma irradiation and tumorigenesis.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 4. The construct was electroporated into 129S1/Sv-p⁺ Tyr⁺ Kitl⁺ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to C57BL/6 female mice. Heterozygotes were bred to generate homozygotes. The mice were then backcrossed to C57BL/6 for 11 generations prior to their arrival at The Jackson Laboratory.

Allele

Symbol: Ing1^tm1Avg
Name: targeted mutation 1, A V Gudkov
MGI accession ID: MGI:3619526
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ing1
Marker name: inhibitor of growth family, member 1
Chromosome: 8
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: A targeting vector was designed to replace exon 4, common to all transcripts and containing most of the protein coding sequences including the conserved PHD finger domain, with a neomycin resistance gene. Transcript was not detected in mutant MEFS in Northern blot analysis. Western blot failed to detect protein in mutants as well.