CHARACTERIZATION OF THE HUNTINGTONS-DISEASE (HD) GENE HOMOLOG IN THE ZEBRAFISH DANIO-RERIO

The Huntington's disease (HD) gene contains a trinucleotide repeat tha t is expanded and unstable in patients with the disease (HDCRG, 1993). As the first step toward investigating a potential role for this gene in early vertebrate development, we isolated the homolog of the Hunti ngton's disease (ZHD) cDNA in zebrafish. This cDNA encodes a predicted protein product of 3121 amino acids with 70% identity to human huntin gtin. The first exon is predicted to encode four glutamines, followed by only one proline, demonstrating that the polymorphic polyproline st retch found in mammalian HD sequences is absent in the fish. We sequen ced approximately 900 bp upstream from the predicted start codon and f ound that it lacks a TATA box, CCAAT box, or Spl binding sites. Wester n blot analysis revealed that the protein is expressed at a high level in late embryonic development and at moderate levels in the adult hea d. (C) 1998 Elsevier Science B.V. All rights reserved.