Cutting edge: Hypermutation in Ig V genes from mice deficient in the MLH1 mismatch repair protein

During somatic hypermutation of Ig V genes, mismatched nucleotide substitut ions become candidates for removal by the DNA mismatch repair pathway. Prev ious studies have shown that V genes from mice deficient for the MSH2 and P MS2 mismatch repair proteins have frequencies of mutation that are comparab le with those from wild-type (wt) mice; however, the pattern of mutation is altered. Because the absence of MSH2 and PMS2 produced different mutationa l spectra, we examined the role of another protein involved in mismatch rep air, MLH1, on the frequency and pattern of hypermutation. MLH1-deficient mi ce 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 pat tern of mutation in Mlh1(-/-) clones was similar to wt clones. These findin gs suggest that the MLH1 protein has no direct effect on the mutational spe ctrum.