Homozygous knockout mutants exhibit increased mortality induced by gamma-irradiation, increased B cell derived lymphoma incidence, splenomegaly, and premature death.
Andrei Gudkov, Cleveland Clinic Foundation
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.
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 Name||targeted mutation 1, A V Gudkov|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ing1, inhibitor of growth family, member 1|
|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.|
|Mutations Made By|| |
Julia Kichina, Cleveland Clinic Foundation
When maintaining a live colony, these mice are bred as homozygotes. The donating investigator used a homozygous X homozygous breeding scheme. Female homozygous mice may neglect or destroy litters.
When using the Ing1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #007263 in your Materials and Methods section.