Altered Ig Hypermutation Pattern and Frequency in Complementary Mouse Models of DNA Polymerase ζ Activity
| Autor: | Ming-Lang Zhao, Janssen Daly, Danielle L. Watt, Marilyn Diaz, Thomas A. Kunkel, Madhumita Ray, Katarzyna Bebenek, Kathleen Richter, Chuancang Jiang, W. Glenn McGregor |
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| Rok vydání: | 2012 |
| Předmět: |
DNA polymerase
Protein subunit Immunology Gene Rearrangement B-Lymphocyte Heavy Chain Somatic hypermutation Mice Transgenic DNA-Directed DNA Polymerase medicine.disease_cause Article Mice Conditional gene knockout Homologous chromosome medicine Animals Immunology and Allergy Gene Knock-In Techniques Mutation frequency Gene Mice Knockout B-Lymphocytes Mutation biology Molecular biology Enzyme Activation Mice Inbred C57BL Models Animal biology.protein Somatic Hypermutation Immunoglobulin |
| Zdroj: | The Journal of Immunology. 188:5528-5537 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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