Gene Symbol: Six5
Description: sine oculis-related homeobox 5
Alias: Dmahp, MDMAHP, TrexBF, homeobox protein SIX5, DM locus-associated homeodomain protein homolog, sine oculis homeobox homolog 5, sine oculis-related homeobox 5 homolog
Species: mouse
Products:     Six5

Top Publications

  1. Matynia A, Ng C, Dansithong W, Chiang A, Silva A, Reddy S. Muscleblind1, but not Dmpk or Six5, contributes to a complex phenotype of muscular and motivational deficits in mouse models of myotonic dystrophy. PLoS ONE. 2010;5:e9857 pubmed publisher
    ..Decreased levels of DMPK (Dystrophia Myotonica-protein kinase), SIX5, a transcription factor or MBNL1 (Muscleblind-like 1), an RNA splice regulator have been demonstrated to contribute ..
  2. Boucher C, King S, Carey N, Krahe R, Winchester C, Rahman S, et al. A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat. Hum Mol Genet. 1995;4:1919-25 pubmed
    ..RT-PCR analysis shows that this gene, which we have called DM locus-associated homeodomain protein (DMAHP), is expressed in a number of human tissues, including skeletal muscle, heart and brain.
  3. Ohto H, Kamada S, Tago K, Tominaga S, Ozaki H, Sato S, et al. Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya. Mol Cell Biol. 1999;19:6815-24 pubmed
    ..Coexpression of Six2, Six4, or Six5 induced nuclear translocation of Eya1, Eya2, and Eya3, which were otherwise distributed in the cytoplasm...
  4. Sarkar P, Appukuttan B, Han J, Ito Y, Ai C, Tsai W, et al. Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts. Nat Genet. 2000;25:110-4 pubmed
    ..expansion located in the 3' untranslated region of DMPK and 5' of a homeodomain-encoding gene, SIX5 (formerly DMAHP; refs 2-5). There are three mechanisms by which CTG expansion can result in DM...
  5. Ozaki H, Watanabe Y, Takahashi K, Kitamura K, Tanaka A, Urase K, et al. Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development. Mol Cell Biol. 2001;21:3343-50 pubmed
    ..g., myogenin and NeuroD3 (neurogenin1), were normal. Our results indicate that Six4 is not essential for mouse embryogenesis and suggest that other members of the Six family seem to compensate for the loss of Six4. ..
  6. Wakimoto H, Maguire C, Sherwood M, Vargas M, Sarkar P, Han J, et al. Characterization of cardiac conduction system abnormalities in mice with targeted disruption of Six5 gene. J Interv Card Electrophysiol. 2002;7:127-35 pubmed
    ..protein kinase (DMPK); second, decreased transcription of a neighboring homeodomain-encoding gene, Six5 (or DMAHP), and third, transdominant effects of the RNA and regulation of splicing associated with expression of expanded ..
  7. Yajima H, Motohashi N, Ono Y, Sato S, Ikeda K, Masuda S, et al. Six family genes control the proliferation and differentiation of muscle satellite cells. Exp Cell Res. 2010;316:2932-44 pubmed publisher
    ..Overexpression of Six4 and Six5 repressed the proliferation and differentiation of satellite cells...
  8. Murakami Y, Ohto H, Ikeda U, Shimada K, Momoi T, Kawakami K. Promoter of mDMAHP/Six5: differential utilization of multiple transcription initiation sites and positive/negative regulatory elements. Hum Mol Genet. 1998;7:2103-12 pubmed
    We analyzed the expression of mouse DMAHP / Six5 (the myotonic dystrophy-associated homeodomain protein gene) during embryogenesis and in various tissues by northern blotting...
  9. Sarkar P, Paul S, Han J, Reddy S. Six5 is required for spermatogenic cell survival and spermiogenesis. Hum Mol Genet. 2004;13:1421-31 pubmed
    ..DM1 results from a CTG expansion that causes transcriptional silencing of the flanking SIX5 allele. Loss of Six5 results in male sterility and a progressive decrease in testicular mass with age...

Scientific Experts

More Information


  1. Kobayashi M, Osanai H, Kawakami K, Yamamoto M. Expression of three zebrafish Six4 genes in the cranial sensory placodes and the developing somites. Mech Dev. 2000;98:151-5 pubmed
    ..six4.2 is expressed in the presomitic mesoderm, somites and pectoral fin bud. six4.3 appears to be a unique member of the Six4 proteins and is expressed ubiquitously at gastrulation and later in the tectum. ..
  2. Coletta R, McCoy E, Burns V, Kawakami K, McManaman J, Wysolmerski J, et al. Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis. BMC Dev Biol. 2010;10:4 pubmed publisher
    ..However, because Six1 is highly expressed in the developing mammary gland, and because it has been implicated in the expansion of mammary stem cells, targeting Six1 as an anti-cancer therapy may have unwanted side effects in the breast...
  3. Ikeda K, Watanabe Y, Ohto H, Kawakami K. Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol Cell Biol. 2002;22:6759-66 pubmed
    ..This work provides fundamental information on the role and the mechanism of action of this gene cassette in tissue differentiation and organogenesis. ..
  4. Kawakami K, Ohto H, Takizawa T, Saito T. Identification and expression of six family genes in mouse retina. FEBS Lett. 1996;393:259-63 pubmed
    ..They are Six2, Six3 alpha and Six3 beta (which are derived from alternative splicing forms), Six5, and AREC3/Six4...
  5. Personius K, Nautiyal J, Reddy S. Myotonia and muscle contractile properties in mice with SIX5 deficiency. Muscle Nerve. 2005;31:503-5 pubmed
    ..Heterozygous loss of SIX5 in mice causes cataracts and cardiac conduction disease, and homozygous loss also leads to sterility and decreased ..
  6. Himeda C, Ranish J, Angello J, Maire P, Aebersold R, Hauschka S. Quantitative proteomic identification of six4 as the trex-binding factor in the muscle creatine kinase enhancer. Mol Cell Biol. 2004;24:2132-43 pubmed
    ..After selectively enriching for the Trex-binding factor (TrexBF) using magnetic beads coupled to oligonucleotides containing either wild-type or mutant Trex sites, quantitative ..
  7. Klesert T, Cho D, Clark J, Maylie J, Adelman J, Snider L, et al. Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy. Nat Genet. 2000;25:105-9 pubmed
    ..We, and others, have demonstrated that repeat expansion decreases expression of the adjacent gene SIX5 (refs 7,8), which encodes a homeodomain transcription factor...
  8. Spitz F, Demignon J, Porteu A, Kahn A, Concordet J, Daegelen D, et al. Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site. Proc Natl Acad Sci U S A. 1998;95:14220-5 pubmed
    ..Altogether these results establish Six homeoproteins as a family of transcription factors controlling muscle formation through activation of one of its key regulators, myogenin. ..
  9. Soker T, Dalke C, Puk O, Floss T, Becker L, Bolle I, et al. Pleiotropic effects in Eya3 knockout mice. BMC Dev Biol. 2008;8:118 pubmed publisher
    ..Therefore, future investigations of Eya3 function should focus on aging mice. ..
  10. Yajima H, Kawakami K. Low Six4 and Six5 gene dosage improves dystrophic phenotype and prolongs life span of mdx mice. Dev Growth Differ. 2016;58:546-61 pubmed publisher
    ..We demonstrated previously the involvement of homeobox transcription factors, SIX1, SIX4 and SIX5, in the coordinated proliferation and differentiation of isolated satellite cells in vitro...
  11. Sato S, Nakamura M, Cho D, Tapscott S, Ozaki H, Kawakami K. Identification of transcriptional targets for Six5: implication for the pathogenesis of myotonic dystrophy type 1. Hum Mol Genet. 2002;11:1045-58 pubmed
    ..The repeat expansion suppresses the expression of the homeobox gene SIX5. We describe here an experimental system to identify downstream transcriptional targets of mouse Six5 in order to ..
  12. Mistry D, Moorman J, Reddy S, Mounsey J. Skeletal muscle Na currents in mice heterozygous for Six5 deficiency. Physiol Genomics. 2001;6:153-8 pubmed
    ..between the myotonic dystrophy protein kinase gene (Dmpk), which encodes a serine-threonine protein kinase, and the Six5 gene, which encodes a homeodomain protein...
  13. Ohto H, Takizawa T, Saito T, Kobayashi M, Ikeda K, Kawakami K. Tissue and developmental distribution of Six family gene products. Int J Dev Biol. 1998;42:141-8 pubmed
    ..b>Six5 was the dominant isoform observed in the adult kidney, liver and lung but not in the brain...
  14. Kutejova E, Engist B, Mallo M, Kanzler B, Bobola N. Hoxa2 downregulates Six2 in the neural crest-derived mesenchyme. Development. 2005;132:469-78 pubmed
    ..Furthermore, we demonstrate that Hoxa2 regulation of Six2 is confined to a 0.9 kb fragment of the Six2 promoter and that Hoxa2 binds to this promoter region. These results strongly suggest that Six2 is a direct target of Hoxa2. ..
  15. Nonomura K, Takahashi M, Wakamatsu Y, Takano Yamamoto T, Osumi N. Dynamic expression of Six family genes in the dental mesenchyme and the epithelial ameloblast stem/progenitor cells during murine tooth development. J Anat. 2010;216:80-91 pubmed publisher
    ..We found dynamic expression patterns for Six1, Six2, Six4 and Six5 in the oral epithelium and mesenchymal cells with distinct expression patterns at the early stage before ..
  16. Heath S, Carne S, Hoyle C, Johnson K, Wells D. Characterisation of expression of mDMAHP, a homeodomain-encoding gene at the murine DM locus. Hum Mol Genet. 1997;6:651-7 pubmed
    We examined the expression of the murine homologue of myotonic dystrophy associated homeodomain protein (mDMAHP) using two different strategies...