Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter.

Abstract

Although it is likely that a highly complex network of transcription factors acts in concert during mammalian brain development, relatively few such genes have been characterized to date. We describe here a novel murine homeobox gene, denoted Gtx, which in adult animals is specifically expressed within glial cells of the central nervous system, including the forebrain, and in germ cells of the testis. Gtx resides on chromosome 7 and does not cosegregate with any previously mapped homeobox gene. The amino acid sequence of the predicted protein encoded by Gtx is highly divergent from that of any other known homeobox genes. The Gtx homeodomain contains unique residues at positions predicted to contact DNA bases. It did not bind to known target sites for other homeobox genes in vitro but bound with high affinity to the MEF‐2 motif, a binding site for the serum response factor‐related proteins. GTX efficiently competed with RSRF to bind the MEF‐2 element in vitro. Co‐transfection of Gtx prevented the serum‐induced activation of the MEF‐2‐containing reporter genes. Although the true biological role of Gtx is not known, these results suggest that Gtx is a novel cell‐type specific homeobox gene that has the potential to act as a transcriptional repressor for a subset of serum‐inducible genes.

CNS Myelin Paranodes Require Nkx6-2 Homeoprotein Transcriptional Activity for Normal Structure

“…1f, Ϫ/Ϫ) reveals strong ␤-galactosidase expression in all major CNS white matter tracts as shown previously for endogenous Nkx6-2 expression (Komuro et al, 1993;Awatramani et al, 1997). Figure 1g shows ␤-galactosidase-positive cells exhibiting the canonical morphology of myelinating oligodendrocytes (Gow et al, 1992) in and around striatal axons (white arrowhead), which demonstrates that the presence of the lacZ sequence does not appreciably alter cell-type specificity.…”

Evidence That the Homeodomain Protein Gtx Is Involved in the Regulation of Oligodendrocyte Myelination

“…The transcription factor Gtx, a novel member of the homeodomain family, has been shown to be expressed in white matter in adult rodents (Komuro et al, 1993). In this paper we have extended this initial observation by investigating in detail the timing of Gtx expression in brain and in cultured oligodendrocytes.…”

“…Furthermore, both proteins contain a conserved decapeptide sequence, found in the N-terminal region of the N K family of homeodomain proteins. No other homeodomain protein, including other members of the N K class, shares more than 60% homology with the homeodomain of either Gtx or Nkx6.1 (Komuro et al, 1993). German and colleagues have recently identified a mouse protein with a homeodomain that is identical to Nkx6.1, suggesting that it is the mouse Nkx6.1 homolog (M. S. German, personal communication).…”

The Gtx Homeodomain Transcription Factor Exerts Neuroprotection Using Its Homeodomain

“…GTX, a neuronal homeobox gene, has been isolated from the postnatal mouse brain (1) and is expressed in differentiated oligodendrocytes with its potential role for myelinization (2,3). It is also termed as Nkx6.2.…”

“…Alzheimer's disease (AD) 1 is the most prevalent neurodegenerative disease, for which a curative therapy has not yet been developed. Three kinds of known mutant genes cause early onset familial AD (FAD): mutants of amyloid-␤ precursor protein (A␤PP), presenilin (PS)1, and PS2, each of which has been shown to cause neuronal cell death (9 -15).…”