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

摘要

GA binding protein (GABP) is a ubiquitously expressed Ets family transcription factor that consists of two subunits, GABPα and GABPβ. GABPα binds to DNA, and GABPβ heterodimerizes with GABPα and possesses the ability to transactivate target genes. Our previous studies using GABPα-deficient mice revealed that GABPα 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 α2β2 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 GABPα/β complex.