Mutant mice have impaired innate host defense response and are more susceptible to bacterial infection of the small intestine mucosal epithelium. Wound repair (reepithelialization) is defective and the mice show reduced apoptosis in prostrate and pancreatic tissue. This mutant mouse strain may be useful in studies related to intestinal and pancreatic tumorigenesis, epithelial wound repair, inflammation and mucosal immune response.
William C. Parks, University of Washington
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by Northern blot analysis of the small intestine. Immunohistochemical analysis of intestinal tissue from homozygotes does not detect the gene product (protein) in Paneth cells. Mutant mice have impaired innate host defense response due to the lack of mature crypt defensin proteins in intestinal epithelium. These mice are more susceptible to bacterial infection of the small intestine mucosal epithelium. Wound repair (reepithelialization) and neutrophil infiltration following respiratory airway injury is defective. Apoptosis is reduced in prostate tissue following castration, and in pancreatic acinar cells following pancreatic duct ligation. This mutant mouse strain may be useful in studies related to intestinal and pancreatic tumorigenesis, epithelial wound repair, inflammation and mucosal immune response.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 95 nucleotides in exon 4. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The donating investigator reported that the resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 11 generations (January 2004; see SNP note below). Heterozygotes were bred to generate homozygotes.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Lynn M Matrisian|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||MAT-; mmp-7-; MMP7-; Mmp7tm1vu|
|Gene Symbol and Name||Mmp7, matrix metallopeptidase 7|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A neomycin resistance cassette replaced approximately 95 nucleotides of coding sequence in exon 4 of the gene. No transcript for the targeted gene was detectable by Northern blot analysis of RNA from the small intestine of homozygous mutant mice.|
|Mutations Made By|| |
Carole Wilson and Lynn Matrisian, Univ. Washington School of Medicine
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