Characterization of the zebrafish atxn1/axh gene family

Kerri M. Carlson, Laura Melcher, Shaojuan Lai, Huda Y. Zoghbi, H. Brent Clark, Harry T Orr

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14 Scopus citations


In mammals, ataxin-1 (ATXN1) is a member of a family of proteins in which each member contains an AXH domain. Expansion of the polyglutamine tract in ATXN1 causes the neurodegenerative disease, spinocerebellar ataxia type 1 (SCA1) with prominent cerebellar pathology. Toward a further characterization of the genetic diversification of the ATXN1/AXH gene family, we identified and characterized members of this gene family in zebrafish, a lower vertebrate with a cerebellum. The zebrafish genome encodes two ATXN1 homologs, atxn1a and atxn1b, and one ATXN1L homolog, atxn1l. Key biochemical features of the human ATXN1 protein not seen in the invertebrate homologs (a nuclear localization sequence and a site of phosphorylation at serine 776) are conserved in the zebrafish homologs, and all three zebrafish Atxn1/Axh proteins behave similarly to their human counterparts in tissue-culture cells. Importantly, each of the three homologs is expressed in the zebrafish cerebellum, which in humans, is a prominent site of SCA1 pathogenesis. In addition, atxn1a and atxn1b are expressed in the developing zebrafish cerebellum. These data show that in zebrafish, a lower vertebrate, the complexity of the atxn1/axh gene family is more similar to higher vertebrates than invertebrates with a simple central nervous system and suggests a relationship between the diversification of the ATXN1/AXH gene family and the development of a complex central nervous system, including a cerebellum.

Original languageEnglish (US)
Pages (from-to)313-323
Number of pages11
JournalJournal of Neurogenetics
Issue number3
StatePublished - Jan 2009

Bibliographical note

Funding Information:
The authors thank the University of Minnesota Zebrafish Core Facility for handling the zebrafish colony and for their helpful advice and also Dr. Steve Ekker PhD, for his helpful discussion. This work was supported by a National Ataxia Foundation Postdoctoral Fellowship (KMC) and National Institute of Health grants NS022920 and NS045667 (HTO).


  • AXH
  • Ataxin-1
  • Ataxin-1 like
  • Danio rerio
  • SCA1


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