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Gene MAR Regulates the Probability of Premature V-J Joining and Somatic Hypermutation1
*
Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75235; and
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109
The Ig
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.
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