Genetic isolation and characterization of a splicing mutant of zebrafish dystrophin
- Authors
- 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.
- ID
- ZDB-PUB-110426-1
- 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.