ZFIN ID: ZDB-PUB-110426-1
Genetic isolation and characterization of a splicing mutant of zebrafish dystrophin
Guyon, J.R., Goswami, J., Jun, S.J., Thorne, M., Howell, M., Pusack, T., Kawahara, G., Steffen, L.S., Galdzicki, M., and Kunkel, L.M.
Date: 2009
Source: Human molecular genetics   18(1): 202-211 (Journal)
Registered Authors: Guyon, Jeff, Kunkel, Louis M., Steffen, Leta Suzanne
Keywords: none
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
PubMed: 18957474 Full text @ Hum. Mol. Genet.

Sapje-like (sapcl100) 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.