Homozygous mutants develop inflammatory bowel disease, diarrhea, and colorectal hyperplasia with occasional anorectal prolapse. They also display mild liver injury and a very high sensitivity to toxins and apoptotic stimuli.
M. Bishr Omary, Stanford University & Palo Alto VA Medic
Homozygous mutants display an incompletely penetrant, reduced viability that is genetic background dependent. On this FVB congenic background, approximately half of homozygous mutant pups die during embryonic development due to placental insufficiency. Maternal TNF (tumor necrosis factor) and TNFR2 (TNFRSF1B, tumor necrosis factor receptor superfamily, member 1b) influence survival of null embyos. Surviving homozygous females have markedly reduced productivity, but males are fertile. Homozygous adult mice develop inflammatory bowel disease, diarrhea, and colorectal hyperplasia with occasional anorectal prolapse. Lesions affect the cecum, remaining colon and rectum, but only minimally affect the small intestine. Elongation of the colonic crypts is accompanied by an inflammation of the lamina propria and submucosa. Livers from homozygous mutant mice display mild injury under basal conditions but a very high sensitivity to toxins and apoptotic stimuli. Minor liver and intestinal sensitivity have been reported in heterozygotes. This strain may be useful as model of inflammatory bowel disease or for its predisposition to liver injury. Other glandular organs in these mice may be useful subjects for study.
A targeting vector was designed to replace most of the first exon, including the ATG translation initiation codon, with a neomycin resistance cassette. The linearized vector was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6 blastocysts. C57BL/6 and 129 mixed background animals were backcrossed at least six times to FVB/N prior to arrival at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Robert G Oshima|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||K8-; mK8 -|
|Gene Symbol and Name||Krt8, keratin 8|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A neomycin resistance cassette replaced a DNA segment containing most of the first exon including the translation initiation codon. Northern blot analysis on RNA isolated from gut, liver, kidney and spleen demonstrated that an aberrant transcript was made in gut, but no transcript was detectable elsewhere. Immunohistochemistry on sections of intestine of homozygous mice confirmed that no detectable protein was expressed from this allele.|
|Mutations Made By|| |
Diana Toivola, Stanford University
When maintained as a live colony, heterozygotes may be used as breeders. Homozygous females are considered to be "infertile", but homozygous males can breed.
When using the mK8- mouse strain in a publication, please cite the originating article(s) and include JAX stock #007031 in your Materials and Methods section.