Hypermutation in Ig V genes from mice deficient in the MLH1 mismatch repair protein.
During somatic hypermutation of Ig V genes, mismatched nucleotide substitutions become candidates for removal by the DNA mismatch repair pathway. Previous studies have shown that V genes from mice deficient for the MSH2 and PMS2 mismatch repair proteins have frequencies of mutation that are comparable with those from wild-type (wt) mice; however, the pattern of mutation is altered. Because the absence of MSH2 and PMS2 produced different mutational spectra, we examined the role of another protein involved in mismatch repair, MLH1, on the frequency and pattern of hypermutation. MLH1-deficient mice were immunized with oxazolone Ag, and splenic B cells were analyzed for mutations in their V kappa Ox1 light chain genes. Although the frequency of mutation in MLH1-deficient mice was twofold lower than in wt mice, the pattern of mutation in Mlh1-/- clones was similar to wt clones. These findings suggest that the MLH1 protein has no direct effect on the mutational spectrum.
Phung
Q H
QH
Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Winter
D B
DB
Alrefai
R
R
Gearhart
P J
PJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001482:Base Composition / Q000276:immunology; D020137:Base Pair Mismatch / Q000276:immunology*; D002352:Carrier Proteins; D002999:Clone Cells / Q000276:immunology; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000276:immunology*; D005803:Genes, Immunoglobulin; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D000070957:MutL Protein Homolog 1; D009154:Mutation / Q000276:immunology*; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007135:Immunoglobulin Variable Region; C501485:Mlh1 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1