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Mol. Cell. Biol. doi:10.1128/MCB.01855-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Targeting the GABP1L isoform does not perturb lymphocyte development and function

Department of Microbiology, Department of Obstetrics and Gynecology, Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242; Laboratory of Molecular Immunology, Transgenic Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674

^* To whom correspondence should be addressed. Email: hai-hui-xue{at}uiowa.edu.

	Abstract

GA binding protein (GABP) is a ubiquitously expressed Ets family transcription factor that consists of two subunits, GABP and GABP. GABP binds to DNA, and GABP heterodimerizes with GABP and possesses the ability to transactivate target genes. Our previous studies using GABP-deficient mice revealed that GABP is required for the development of both T and B cells. Two splice variants of GABP are generated from the Gabpb1 locus, and differ in their carboxy-terminal lengths and sequences. The longer isoform (GABP1L) can homodimerize and thus form ₂₂ tetramers depending on the gene context, whereas the shorter isoform (GABP1S) cannot. In this study, we generated mice that are deficient in GABP1L but retain expression of GABP1S. Surprisingly, GABP1L^-/- mice had normal T and B cell development, and mature T and B cells showed normal responses to various stimuli. In contrast, targeting both GABP1L and GABP1S resulted in early embryonic lethality. Because of its incapability of forming homodimers, GABP1S has been suspected to have a dominant negative role in regulating GABP target genes. Our findings argue against such a possibility, and rather suggest that GABP1S has a critical role in maintaining the transcriptional activity of the GABP/ complex.

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