TY - JOUR
T1 - Cutting edge
T2 - Hypermutation in Ig V genes from mice deficient in the MLH1 mismatch repair protein
AU - Phung, Quy H.
AU - Winter, David B.
AU - Alrefai, Rudaina
AU - Gearhart, Patricia J.
PY - 1999/3/15
Y1 - 1999/3/15
N2 - 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 mutations 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 VκOx1 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.
AB - 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 mutations 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 VκOx1 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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M3 - Article
C2 - 10092760
AN - SCOPUS:0033558532
VL - 162
SP - 3121
EP - 3124
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -