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PMID: 14673163 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mice deficient for the ets transcription factor elk-1 show normal immune responses and mildly impaired neuronal gene activation.

Molecular and cellular biology ·Vol. 24 ·No. 1 ·2004-01-00 ·Pages 294-305

Cesari F, Brecht S, Vintersten K, Vuong LG, Hofmann M, Klingel K, Schnorr JJ, Arsenian S, Schild H, Herdegen T, Wiebel FF, Nordheim A

Abstract

The transcription factor Elk-1 belongs to the ternary complex factor (TCF) subfamily of Ets proteins. TCFs interact with serum response factor to bind jointly to serum response elements in the promoters of immediate-early genes (IEGs). TCFs mediate the rapid transcriptional response of IEGs to various extracellular stimuli which activate mitogen-activated protein kinase signaling. To investigate physiological functions of Elk-1 in vivo, we generated Elk-1-deficient mice by homologous recombination in embryonic stem cells. These animals were found to be phenotypically indistinguishable from their wild-type littermates. Histological analysis of various tissues failed to reveal any differences between Elk-1 mutant and wild-type mice. Elk-1 deficiency caused no changes in the proteomic displays of brain or spleen extracts. Also, no immunological defects could be detected in mice lacking Elk-1, even upon infection with coxsackievirus B3. In mouse embryonic fibroblasts, Elk-1 was dispensable for c-fos and Egr-1 transcriptional activation upon stimulation with serum, lysophosphatidic acid, or tetradecanoyl phorbol acetate. However, in brains of Elk-1-deficient mice, cortical and hippocampal CA1 expression of c-fos, but not Egr-1 or c-Jun, was markedly reduced 4 h following kainate-induced seizures. This was not accompanied by altered patterns of neuronal apoptosis. Collectively, our data indicate that Elk-1 is essential neither for mouse development nor for adult life, suggesting compensatory activities by other TCFs.

MeSH Terms
Animals DNA-Binding Proteins/metabolism Early Growth Response Protein 1 Immediate-Early Proteins Immune System/immunology Mice Mice, Knockout Neurons/metabolism Proto-Oncogene Proteins/biosynthesis,deficiency,genetics Proto-Oncogene Proteins c-fos/metabolism T-Lymphocytes/metabolism Transcription Factors/metabolism ets-Domain Protein Elk-1
Chemicals
DNA-Binding Proteins Early Growth Response Protein 1 Egr1 protein, mouse Elk1 protein, mouse Immediate-Early Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-fos Transcription Factors ets-Domain Protein Elk-1
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Cesari Francesca
Abteilung Molekularbiologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Brecht Stephan
Vintersten Kristina
Vuong Lam Giang
Hofmann Matthias
Klingel Karin
Schnorr Jens-Jörg
Arsenian Sergei
Schild Hansjörg
Herdegen Thomas
Wiebel Franziska F
Nordheim Alfred
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.1.294-305.2004
Published
2004-01-00
Pages
294-305
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC303347
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.1.294-305.2004 PMC Full Text View journal details
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