Mice Deficient for the Ets Transcription Factor Elk-1 Show Normal Immune Responses and Mildly Impaired Neuronal Gene Activation

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 immediateearly 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 kainateinduced 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.

c-Jun N-terminal Kinase 3 Deficiency Protects Neurons from Axotomy-induced Death in Vivo through Mechanisms Independent of c-Jun Phosphorylation

“…Because protection afforded by JNK3 deficiency was not accompanied by reduced c-Jun phosphorylation following facial axotomy, we asked whether other potential JNK targets may be modulated and required for neuronal death. We examined additional select transcription factors, ATF2 and Elk1, which are also regulated by the JNKs (39,40). However, we could not detect any increased phosphorylation or induction of these factors following axotomy 24 h following axotomy when c-Jun activation was pronounced (data not shown).…”

Ternary Complex Factors SAP-1 and Elk-1, but Not Net, Are Functionally Equivalent in Thymocyte Development

“…In contrast, SAP-1 is not required for negative selection, the ERK-independent process by which thymocytes bearing high self-avidity TCRs are deleted from the T cell repertoire (2,3). In contrast, Elk-1 inactivation causes no obvious phenotype, whereas the Net d mutation leads to lymphangiectasia (5,6).…”

“…Mice SAP-1 2/2 , Elk-1 2/2 , and Net d animals (2,5,6), kept under specificpathogen-free conditions, were backcrossed to C57/BLJ mice (The Jackson Laboratory, Bar Harbor, ME) for a minimum of five generations and were subsequently crossed with OT-II and HY TCR transgenic mice (2). Elk-1 is on the X chromosome; for clarity we refer to Elk-1 nulls as Elk-1 2/2 , regardless of gender, and specify gender in the text and figures when appropriate.…”

MAP Kinase Cascades in Antigen Receptor Signaling and Physiology

“…In contrast to CREB, single deficiency of the Elk members, Elk-1, Elk-3, and Elk-4 led to an apparently normal B cell development. However, considering the structural similarities among these members, it is possible that functional compensation may operate in B cells, thereby tempering the phenotype (Cesari et al, 2004;Costello, Nicolas, Watanabe, Rosewell, & Treisman, 2004). …”