2.50
Hdl Handle:
http://hdl.handle.net/10033/22173
Title:
Serum response factor contributes selectively to lymphocyte development.
Authors:
Fleige, Anne; Alberti, Siegfried; Gröbe, Lothar; Frischmann, Ursula; Geffers, Robert; Müller, Werner; Nordheim, Alfred; Schippers, Angela
Abstract:
Serum response factor (SRF), is a crucial transcription factor for murine embryonic development and for the function of muscle cells and neurons. Gene expression data show that SRF and its transcriptional cofactors are also expressed in lymphocyte precursors and mature lymphocytes. However, the role of SRF in lymphocyte development has not been addressed in vivo so far, attributed in part to early embryonic lethality of conventional Srf-null mice. To determine the in vivo role of SRF in developing lymphocytes, we specifically inactivated the murine Srf gene during T or B cell development using lymphocyte-specific Cre transgenic mouse lines. T cell-specific Srf deletion led to a severe block in thymocyte development at the transition from CD4/CD8 double to single positive stage. The few residual T cells detectable in the periphery retained at least one functional Srf allele, thereby demonstrating the importance of SRF in T cell development. In contrast, deletion of Srf in developing B cells did not interfere with the growth and survival of B cells in general, yet led to a complete loss of marginal zone B cells and a marked reduction of the CD5+ B cell subset. Our study also revealed a contribution of SRF to the expression of the surface molecules IgM, CD19, and the chemokine receptor 4 in B lymphocytes. We conclude that SRF fulfills essential and distinct functions in the differentiation of different types of lymphocytes.
Affiliation:
Department of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Citation:
Serum response factor contributes selectively to lymphocyte development. 2007, 282 (33):24320-8 J. Biol. Chem.
Journal:
The Journal of biological chemistry
Issue Date:
17-Aug-2007
URI:
http://hdl.handle.net/10033/22173
DOI:
10.1074/jbc.M703119200
PubMed ID:
17591768
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
Publications of Dept. Experimental Immunology (EI)

Full metadata record

DC FieldValue Language
dc.contributor.authorFleige, Anne-
dc.contributor.authorAlberti, Siegfried-
dc.contributor.authorGröbe, Lothar-
dc.contributor.authorFrischmann, Ursula-
dc.contributor.authorGeffers, Robert-
dc.contributor.authorMüller, Werner-
dc.contributor.authorNordheim, Alfred-
dc.contributor.authorSchippers, Angela-
dc.date.accessioned2008-04-03T08:37:01Z-
dc.date.available2008-04-03T08:37:01Z-
dc.date.issued2007-08-17-
dc.identifier.citationSerum response factor contributes selectively to lymphocyte development. 2007, 282 (33):24320-8 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid17591768-
dc.identifier.doi10.1074/jbc.M703119200-
dc.identifier.urihttp://hdl.handle.net/10033/22173-
dc.description.abstractSerum response factor (SRF), is a crucial transcription factor for murine embryonic development and for the function of muscle cells and neurons. Gene expression data show that SRF and its transcriptional cofactors are also expressed in lymphocyte precursors and mature lymphocytes. However, the role of SRF in lymphocyte development has not been addressed in vivo so far, attributed in part to early embryonic lethality of conventional Srf-null mice. To determine the in vivo role of SRF in developing lymphocytes, we specifically inactivated the murine Srf gene during T or B cell development using lymphocyte-specific Cre transgenic mouse lines. T cell-specific Srf deletion led to a severe block in thymocyte development at the transition from CD4/CD8 double to single positive stage. The few residual T cells detectable in the periphery retained at least one functional Srf allele, thereby demonstrating the importance of SRF in T cell development. In contrast, deletion of Srf in developing B cells did not interfere with the growth and survival of B cells in general, yet led to a complete loss of marginal zone B cells and a marked reduction of the CD5+ B cell subset. Our study also revealed a contribution of SRF to the expression of the surface molecules IgM, CD19, and the chemokine receptor 4 in B lymphocytes. We conclude that SRF fulfills essential and distinct functions in the differentiation of different types of lymphocytes.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshB-Lymphocytesen
dc.subject.meshCell Differentiationen
dc.subject.meshCell Proliferationen
dc.subject.meshCell Survivalen
dc.subject.meshLymphocyte Subsetsen
dc.subject.meshLymphocytesen
dc.subject.meshMiceen
dc.subject.meshMice, Transgenicen
dc.subject.meshSerum Response Factoren
dc.subject.meshT-Lymphocytesen
dc.titleSerum response factor contributes selectively to lymphocyte development.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.en
dc.identifier.journalThe Journal of biological chemistryen

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