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*
Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224; and
Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21205
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
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.
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