Normal hypermutation in antibody genes from congenic mice defective for DNA polymerase

被引:30
作者
Martomo, SA
Yang, WW
Vaisman, A
Maas, A
Yokoi, M
Hoeijmakers, JH
Hanaoka, F
Woodgate, R
Gearhart, PJ [1 ]
机构
[1] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA
[2] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA
[3] Osaka Univ, Grad Sch Frontier Biosci, Osaka, Japan
[4] Erasmus MC, Ctr Biomed Genet, MGC Dept Cell Biol & Genet, Rotterdam, Netherlands
[5] Japan Sci & Technol Agcy, Solut Oriented Res Sci & Technol, Wako, Saitama, Japan
[6] RIKEN, Discovery Res Inst, Wako, Saitama 35101, Japan
关键词
immunoglobulins; somatic hypermutation; class switch recombination; Pol iota; Pol eta; congenic mice;
D O I
10.1016/j.dnarep.2005.12.006
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Several low fidelity DNA polymerases participate in generating mutations in immunoglobulin genes. Polymerase eta is clearly involved in the process by causing substitutions of A:T base pairs, whereas polymerase iota has a controversial role. Although the frequency of mutations was decreased in the BL2 cell line deficient for polymerase iota, hypermutation was normal in the 129 strain of mice, which has a natural nonsense mutation in the Poli gene. It is possible that the mice compensated for the defect over time, or that polymerase eta substituted in the absence of polymerase iota. To examine polymerase iota in a genetically defined background, we backcrossed the 129 nonsense mutation to the C57BL/6 strain for six generations. Class switch recombination and hypermutation were studied in these mice and in congenic mice doubly deficient for both polymerases iota and eta. The absence of both polymerases did not affect production of IgG1, indicating that these enzymes are not involved in switch recombination. poli(-/-F6) mice had the same types of nucleotide substitutions in variable genes as their C57BL/6 counterparts, and mice doubly deficient for polymeraseS iota and eta had the same mutational spectrum as Polh(-/-) mice. Thus, polymerase iota did not contribute to the mutational spectra, even in the absence of polymerase eta. Published by Elsevier B.V.
引用
收藏
页码:392 / 398
页数:7
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