Altered Ig hypermutation pattern and frequency in complementary mouse models of DNA polymerase ζ activity.
To test the hypothesis that DNA polymerase ζ participates in Ig hypermutation, we generated two mouse models of Pol ζ function: a B cell-specific conditional knockout and a knock-in strain with a Pol ζ mutagenesis-enhancing mutation. Pol ζ-deficient B cells had a reduction in mutation frequency at Ig loci in the spleen and in Peyer's patches, whereas knock-in mice with a mutagenic Pol ζ displayed a marked increase in mutation frequency in Peyer's patches, revealing a pattern that was similar to mutations in yeast strains with a homologous mutation in the gene encoding the catalytic subunit of Pol ζ. Combined, these data are best explained by a direct role for DNA polymerase ζ in Ig hypermutation.
Pubmed ID: 22547703 RIS Download
Animals | B-Lymphocytes | DNA-Directed DNA Polymerase | Enzyme Activation | Gene Knock-In Techniques | Gene Rearrangement, B-Lymphocyte, Heavy Chain | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Models, Animal | Somatic Hypermutation, Immunoglobulin