Mice deficient for the ets transcription factor elk-1 show normal immune responses and mildly impaired neuronal gene activation.
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.
Cesari
Francesca
F
Abteilung Molekularbiologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Brecht
Stephan
S
Vintersten
Kristina
K
Vuong
Lam Giang
LG
Hofmann
Matthias
M
Klingel
Karin
K
Schnorr
Jens-Jörg
JJ
Arsenian
Sergei
S
Schild
Hansjörg
H
Herdegen
Thomas
T
Wiebel
Franziska F
FF
Nordheim
Alfred
A
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D007107:Immune System / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C494113:Elk1 protein, mouse; D017874:Immediate-Early Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1