title: Analysis of mice lacking DNaseI hypersensitive sites at the 5' end of the IgH locus.
abstract: The 5' end of the IgH locus contains a cluster of DNaseI hypersensitive sites, one of which (HS1) was shown to be pro-B cell specific and to contain binding sites for the transcription factors PU.1, E2A, and Pax5. These data as well as the location of the hypersensitive sites at the 5' border of the IgH locus suggested a possible regulatory function for these elements with respect to the IgH locus. To test this notion, we generated mice carrying targeted deletions of either the pro-B cell specific site HS1 or the whole cluster of DNaseI hypersensitive sites. Lymphocytes carrying these deletions appear to undergo normal development, and mutant B cells do not exhibit any obvious defects in V(D)J recombination, allelic exclusion, or class switch recombination. We conclude that deletion of these DNaseI hypersensitive sites does not have an obvious impact on the IgH locus or B cell development.
authors.affiliation: The Howard Hughes Medical Institute, The Children's Hospital, Immune Disease Institute, and Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perlot
authors.forename: Inka
authors.initials: I
authors.lastname: Pawlitzky
authors.forename: John P
authors.initials: JP
authors.lastname: Manis
authors.forename: Ali A
authors.initials: AA
authors.lastname: Zarrin
authors.forename: Peter H
authors.initials: PH
authors.lastname: Brodeur
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003850:Deoxyribonuclease I / Q000378:metabolism*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D005838:Genotype; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D009154:Mutation; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism*; D050441:VDJ Exons / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D014157:Transcription Factors; D003850:Deoxyribonuclease I