title: Evidence that the Igkappa gene MAR regulates the probability of premature V-J joining and somatic hypermutation.
abstract: The Igkappa gene contains an evolutionarily conserved nuclear matrix association region (MAR) adjacent to the intronic enhancer. To test for the function of this MAR, we created mouse lines with a targeted MAR deletion. In MAR knockout animals, the immune system was normal in nearly all respects, including the distributions of various B cell populations and Ab levels. However, in pro-B cells, enhanced rearrangement was noted on the MAR- allele in heterozygotes. In addition, the efficiencies for targeting and generating somatic mutations were reduced on MAR-deleted alleles. These results provide evidence for the MAR negatively regulating the probability of premature rearrangement and positively regulating the probability of somatic hypermutation.
authors.affiliation: Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. b1
authors.forename: M
authors.initials: M
authors.lastname: Yi
authors.forename: P
authors.initials: P
authors.lastname: Wu
authors.forename: K W
authors.initials: KW
authors.lastname: Trevorrow
authors.forename: L
authors.initials: L
authors.lastname: Claflin
authors.forename: W T
authors.initials: WT
authors.lastname: Garrard
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D017124:Conserved Sequence; D019175:DNA Methylation; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis; D011336:Probability; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000302:isolation & purification; D011995:Recombination, Genetic
chemical_list: D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D012333:RNA, Messenger