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 (protein) is detected by Western blot analysis of peripheral blood cells. Male mice homozygous for the mutation are more susceptible to experimentally induced invasive papillomas and fibrosarcomas. Latency of papilloma tumor formation is shorter. Female homozygotes exhibit increased skin cancer incidence when treated with tamoxifen or ovarectomy. Carcinogen administration causes persistent inflammatory response with neutrophil accumulation at the site of injection. Lipopolysaccharide (LPS) challenge causes a two-fold increase in polymorphonuclear cell accumulation in affected lung tissue of male homozygotes. This mutant mouse strain may be useful in studies of carcinogenesis, metastasis, and inflammation.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 2 to 4. The construct was electroporated into 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to C57BL/6 for 10 generations.
|Allele Name||targeted mutation 1, Carlos Lopez-Otin|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||collagenase-2 deficient; MMP-8 KO; Mmp8-; Mmp8tm1Lotn|
|Gene Symbol and Name||Mmp8, matrix metallopeptidase 8|
|Strain of Origin||129X1/SvJ|
|Molecular Note||Part of exon 2 and all of exons 3 and 4 were replaced with a PGK-neomycin gene. Lack of protein product verified by immunofluorescence analysis blood neutrophils and by Western blot analysis.|
|Mutations Made By|| |
Jennifer Cusick, University of Pittsburgh
When maintaining a live colony, these mice are bred as homozygotes.
When using the Mmp8- mouse strain in a publication, please cite the originating article(s) and include JAX stock #005514 in your Materials and Methods section.