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Gene Review

Nkx6-2  -  NK6 homeobox 2

Mus musculus

Synonyms: Gtx, Nkx6.2
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Disease relevance of Nkx6-2

  • In this study, we describe the use of 10 linked copies of the Gtx (homeodomain protein) IRES (abbreviated as SIRES) in place of the encephalomyocarditis (EMCV) IRES in mediating downstream reporter gene expression in cell culture and in vivo [1].

High impact information on Nkx6-2


Biological context of Nkx6-2

  • The involvement of these downstream proteins in cytoskeletal function and cell adhesion reveals mechanisms whereby Nkx6-2 directly or indirectly regulates axon- glial interactions at myelin paranodes [4].
  • The amino acid sequence of the predicted protein encoded by Gtx is highly divergent from that of any other known homeobox genes [3].
  • The absence of detectable phenotypes suggests a redundant function of Nkx6.2 in mouse development [5].
  • rRNA-complementarity in the 5' untranslated region of mRNA specifying the Gtx homeodomain protein: evidence that base- pairing to 18S rRNA affects translational efficiency [6].
  • Various point mutations in the Gtx element and in either the hybrid or wild-type yeast 18S rRNAs confirmed the requirement for an intact complementary match [7].

Anatomical context of Nkx6-2

  • Using a lacZ-knock-in strategy to ablate Nkx6-2, we find that the Nkx6-2 promoter is active embryonically in neuroblasts and postnatally in oligodendrocytes [4].
  • CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure [4].
  • Unexpectedly, we find that the initial expression of Olig2 is left intact in the caudal hindbrain of Nkx6.1/Nkx6.2 compound mutants, and despite this, all somatic motoneurons are missing [8].
  • The redundant activities of Nkx6.1 and Nkx6.2, in turn, are dispensable for visceral motoneuron generation but are necessary to prevent these cells from adopting a parallel program of interneuron differentiation [8].
  • Two closely related transcriptional repressors, Nkx6.2 and Nkx6.1, are expressed by progenitors in overlapping domains of the ventral spinal cord [9].

Other interactions of Nkx6-2

  • The expression of Nkx6.3 overlapped with the expression of Nkx6.2 both in the CNS and in the gut [10].
  • Transient Nkx6.2 expression was also detected in the developing pancreas [10].

Analytical, diagnostic and therapeutic context of Nkx6-2

  • To investigate the role of Nkx6.2 in the control of cell specification and differentiation, we generated mice with null mutations in Nkx6.2 using the standard gene targeting approach [5].


  1. Noninvasive monitoring of target gene expression by imaging reporter gene expression in living animals using improved bicistronic vectors. Wang, Y., Iyer, M., Annala, A.J., Chappell, S., Mauro, V., Gambhir, S.S. J. Nucl. Med. (2005) [Pubmed]
  2. Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Vallstedt, A., Klos, J.M., Ericson, J. Neuron (2005) [Pubmed]
  3. 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. Komuro, I., Schalling, M., Jahn, L., Bodmer, R., Jenkins, N.A., Copeland, N.G., Izumo, S. EMBO J. (1993) [Pubmed]
  4. CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure. Southwood, C., He, C., Garbern, J., Kamholz, J., Arroyo, E., Gow, A. J. Neurosci. (2004) [Pubmed]
  5. Mice lacking the Nkx6.2 (Gtx) homeodomain transcription factor develop and reproduce normally. Cai, J., Qi, Y., Wu, R., Modderman, G., Fu, H., Liu, R., Qiu, M. Mol. Cell. Biol. (2001) [Pubmed]
  6. rRNA-complementarity in the 5' untranslated region of mRNA specifying the Gtx homeodomain protein: evidence that base- pairing to 18S rRNA affects translational efficiency. Hu, M.C., Tranque, P., Edelman, G.M., Mauro, V.P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. An mRNA-rRNA base-pairing mechanism for translation initiation in eukaryotes. Dresios, J., Chappell, S.A., Zhou, W., Mauro, V.P. Nat. Struct. Mol. Biol. (2006) [Pubmed]
  8. Complementary roles for Nkx6 and Nkx2 class proteins in the establishment of motoneuron identity in the hindbrain. Pattyn, A., Vallstedt, A., Dias, J.M., Sander, M., Ericson, J. Development (2003) [Pubmed]
  9. Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification. Vallstedt, A., Muhr, J., Pattyn, A., Pierani, A., Mendelsohn, M., Sander, M., Jessell, T.M., Ericson, J. Neuron (2001) [Pubmed]
  10. Cloning and analysis of Nkx6.3 during CNS and gastrointestinal development. Alanentalo, T., Chatonnet, F., Karlen, M., Sulniute, R., Ericson, J., Andersson, E., Ahlgren, U. Gene Expr. Patterns (2006) [Pubmed]
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