Genetic isolation and characterization of a splicing mutant of zebrafish dystrophin

Hum Mol Genet. 2009 Jan 1;18(1):202-11. doi: 10.1093/hmg/ddn337. Epub 2008 Oct 28.

Abstract

Sapje-like (sap(cl100)) was one of eight potential zebrafish muscle mutants isolated as part of an early-pressure screen of 500 families. This mutant shows a muscle tearing phenotype similar to sapje (dys-/-) and both mutants fail to genetically complement suggesting they have a mutation in the same gene. Protein analysis confirms a lack of dystrophin in developing sapje-like embryos. Sequence analysis of the sapje-like dystrophin mRNA shows that exon 62 is missing in the dystrophin transcript causing exon 63 to be translated out of frame terminating translation at a premature stop codon at the end of exon 63. Sequence analysis of sapje-like genomic DNA identified a mutation in the donor splice junction at the end of dystrophin exon 62. This mutation is similar to splicing mutations associated with human forms of Duchenne Muscular Dystrophy. Sapje-like is the first zebrafish dystrophin splicing mutant identified to date and represents a novel disease model which can be used in future studies to identify therapeutic compounds for treating diseases caused by splicing defects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Conserved Sequence
  • Disease Models, Animal
  • Dystrophin / chemistry
  • Dystrophin / genetics*
  • Dystrophin / metabolism
  • Humans
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / metabolism
  • Mutation*
  • Phenotype
  • RNA Splicing*
  • Sequence Alignment
  • Zebrafish / genetics*
  • Zebrafish / metabolism
  • Zebrafish Proteins / chemistry
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • Dystrophin
  • Zebrafish Proteins