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

Recent studies suggest that DNA polymerase eta (poleta) and DNA polymerase iota (poliota) are involved in somatic hypermutation of immunoglobulin variable genes. To test the role Of poliota in generating mutations in an annual model, we first characterized the biochemical properties of murine poliota. Like its human counter-part, murine poliota is extremely error-prone when catalyzing synthesis on a variety of DNA templates in vitro. Interestingly, when filling in a I base-pair gap, DNA synthesis and subsequent strand displacement was greatest ill the presence of both pols iota and eta. 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 poliota. Analysis of hypermutation in variable genes from 129/SvJ (Poli(-/-)) and C57BL/6J (Pol(+/+)) mice revealed that the overall frequency and spectrum of mutation were normal in poliota-deficient mice. Thus, either poliota does not participate in hypermutation, or its role is nonessential and call be readily assumed by another low-fidelity polymerase.