129-Derived strains of mice are deficient in DNA polymerase ι and have normal immunoglobulin hypermutation

John P. McDonald, Ekaterina G. Frank, Brian S. Plosky, Igor B. Rogozin, Chikahide Masutani, Fumio Hanaoka, Roger Woodgate, Patricia J. Gearhart

Research output: Contribution to journalArticle

Abstract

Recent studies suggest that DNA polymerase η (polη) and DNA polymerase ι (polι) are involved in somatic hypermutation of immunoglobulin variable genes. To test the role of polι in generating mutations in an animal model, we first characterized the biochemical properties of murine polι. Like its human counterpart, murine polι is extremely error-prone when catalyzing synthesis on a variety of DNA templates in vitro. Interestingly, when filling in a 1 base-pair gap, DNA synthesis and subsequent strand displacement was greatest in the presence of both pols ι and η. Genomic sequence analysis of Poli led to the serendipitous discovery that 129-derived strains of mice have a nonsense codon mutation in exon 2 that abrogates production of polι. Analysis of hypermutation in variable genes from 129/SvJ (Poli-/-) and C57BL/6J (Poli+/+) mice revealed that the overall frequency and spectrum of mutation were normal in polι-deficient mice. Thus, either polι does not participate in hypermutation, or its role is nonessential and can be readily assumed by another low-fidelity polymerase.

Original languageEnglish (US)
Pages (from-to)635-643
Number of pages9
JournalJournal of Experimental Medicine
Volume198
Issue number4
DOIs
StatePublished - Aug 18 2003

Keywords

  • Base excision repair
  • Cytosine deamination
  • DNA polymerase η
  • Genomic organization
  • Immunoglobulin variable genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    McDonald, J. P., Frank, E. G., Plosky, B. S., Rogozin, I. B., Masutani, C., Hanaoka, F., Woodgate, R., & Gearhart, P. J. (2003). 129-Derived strains of mice are deficient in DNA polymerase ι and have normal immunoglobulin hypermutation. Journal of Experimental Medicine, 198(4), 635-643. https://doi.org/10.1084/jem.20030767