Combination of 3′ and 5′ IgH regulatory elements mimics the B-specific endogenous expression pattern of IgH genes from pro-B cells to mature B cells in a transgenic mouse model

• Published in: Biochimica et biophysica acta 2003-10, Vol.1642 (3), p.181-190
• Main Authors: Guglielmi, Laurence, Le Bert, Marc, Comte, Isabelle, Dessain, Marie Laure, Drouet, Mireille, Ayer-Le Lievre, Christiane, Cogné, Michel, Denizot, Yves
• Format: Article
• Language: English
• Subjects: 3′LCR; Animals; B lymphocyte; B-Lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; Cell Differentiation; Cell Line; DNA Methylation; Gene Expression Regulation; Gene regulation; Genes, Immunoglobulin; Genes, Immunoglobulin - genetics; Genes, RAG-1; Genes, RAG-1 - genetics; Immunoglobulin Heavy Chains; Immunoglobulin Heavy Chains - genetics; Immunology; Life Sciences; Mice; Mice, Transgenic; Organ Specificity; Regulatory Sequences, Nucleic Acid; Regulatory Sequences, Nucleic Acid - genetics; Spleen; Spleen - cytology; Transgenes; Transgenes - genetics; Transgenic
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2003.08.005

To ensure the B cell differentiation stage specificity of the intronic Eμ element and of the locus control region (LCR) that lies downstream of the IgH chain locus, we generated transgenic mice harboring a V H promoter-GFP reporter gene linked to the 3′LCR region and the Eμ element. By flow cytometry, GFP + lymphocytes were observed amongst pro-B cells (B220 +CD43 +CD117 +) and at all stages of differentiation up to mature B cells (B220 +IgM +IgD +). Expression was strictly confined to cells committed to the B lymphocyte lineage as judged by the lack of GFP +Thy1,2 + cells (T lymphocytes) and GFP +B220 −CD117 +CD43 + cells (uncommitted lymphohematopoietic progenitors). Therefore, the Eμ-GFP-3′LCR transgene is not expressed by hematopoietic stem cells, begins its expression in pro-B cells and is specifically active at all stages of B cell maturation. The combination of 3′ and 5′ IgH regulatory elements thus appears as a potentially useful cassette in transgenes that require a stringent and early B lineage-specific expression.