title: Genomic suppression of murine B29/Ig-beta promoter-driven transgenes.
abstract: Immunoglobulin beta (Ig-beta) is a critical signal transducer of precursor B cell and B cell receptors. B29, the gene coding for Ig-beta, is switched on in progenitor B cells and expressed until the terminal stage of antibody-producing plasma cells. Although several cis-acting elements and transcription factors required for B29 expression have been characterized in cell lines, the in vivo significance of individual motifs located in the 1.2-kb promoter region remained unclear. To address whether this region drives B lineage-specific expression in mice as efficiently as in transfected cell lines, we established transgenic animals carrying the B29 promoter fused to either enhanced green fluorescent protein (EGFP) or the precursor B cell receptor component lambda5. Surprisingly, only minimal levels of B29-derived transcripts were produced in B lymphoid tissues of several independent transgenic lines, and the respective proteins were below the detection limit. In addition, transgenic transcripts were found in testis, kidney and brain. Hence, the 1.2-kb-sized B29 promoter does not define a strong, B lineage-restricted expression unit when randomly integrated into the genome and passed through the murine germ line. Therefore, yet unidentified genomic locus control elements are required to efficiently drive B29 expression in B lymphocytes.
authors.affiliation: Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center for Molecular Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Vettermann
authors.forename: Johannes
authors.initials: J
authors.lastname: Lutz
authors.forename: Manuel
authors.initials: M
authors.lastname: Selg
authors.forename: Michael
authors.initials: M
authors.lastname: Bösl
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051925:CD79 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005260:Female; D023281:Genomics / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology*; D019076:Transgenes
chemical_list: D051925:CD79 Antigens; C497884:Cd79b protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins