This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.01855-07v1 28/13/4300    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Xue, H.-H. Articles by Leonard, W. J. PubMed PubMed Citation Articles by Xue, H.-H. Articles by Leonard, W. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2008, p. 4300-4309, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.01855-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Targeting the GA Binding Protein β1L Isoform Does Not Perturb Lymphocyte Development and Function

Department of Microbiology,¹ Department of Obstetrics and Gynecology,⁴ Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242,⁵ Laboratory of Molecular Immunology,² Transgenic Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674³

Received 11 October 2007/ Returned for modification 21 November 2007/ Accepted 13 April 2008

GA binding protein (GABP) is a ubiquitously expressed Ets family transcription factor that consists of two subunits, GABP and GABPβ. GABP binds to DNA, and GABPβ 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 GABPβ are generated from the Gabpb1 locus and differ in their carboxy-terminal lengths and sequences. The longer isoform (GABPβ1L) can homodimerize and thus form ₂β₂ tetramers depending on the gene context, whereas the shorter isoform (GABPβ1S) cannot. In this study, we generated mice that are deficient in GABPβ1L but that retain the expression of GABPβ1S. Surprisingly, GABPβ1L^–/– mice had normal T- and B-cell development, and mature T and B cells showed normal responses to various stimuli. In contrast, targeting both GABPβ1L and GABPβ1S resulted in early embryonic lethality. Because of its incapability of forming homodimers, GABPβ1S 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 GABPβ1S has a critical role in maintaining the transcriptional activity of the GABP/β complex.

Published ahead of print on 21 April 2008.