PUBLICATION
An altered intron inhibits synthesis of the acetylcholine receptor alpha-subunit in the paralyzed zebrafish mutant nic1
- Authors
- Sepich, D.S., Wegner, J., O'Shea, S., and Westerfield, M.
- ID
- ZDB-PUB-980212-2
- Date
- 1998
- Source
- Genetics 184: 361-372 (Journal)
- Registered Authors
- O'Shea, S. Anni, Sepich, Diane, Wegner, Jeremy, Westerfield, Monte
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Base Sequence
- Gene Deletion
- Introns/genetics*
- Molecular Sequence Data
- Paralysis
- Phenotype
- Polymorphism, Restriction Fragment Length
- RNA, Messenger/metabolism*
- Receptors, Cholinergic/biosynthesis
- Receptors, Cholinergic/genetics*
- Sequence Alignment
- Sequence Homology, Amino Acid
- Sequence Homology, Nucleic Acid
- Zebrafish/genetics*
- PubMed
- 9475746 Full text @ Genetics
Citation
Sepich, D.S., Wegner, J., O'Shea, S., and Westerfield, M. (1998) An altered intron inhibits synthesis of the acetylcholine receptor alpha-subunit in the paralyzed zebrafish mutant nic1. Genetics. 184:361-372.
Abstract
The acetylcholine receptor (AChR), an oligomeric protein composed of five subunits, is a component of the postsynaptic membrane at the vertebrate neuromuscular junction that plays a central role in synaptic transmission. The zebrafish mutation nic1 blocks the expression of functional and clustered nicotinic muscle AChRs. To understand the mechanisms underlying this lack of AChRs, we characterized the molecular defect in nic1 mutants. Our results suggest that the mutation affects the gene coding for the alpha-subunit of the AChR. Southern blot hybridization and DNA sequence analyses showed that the nic1 AChR alpha-subunit gene lacks part of intron 6 where the splicing branchpoint normally forms. Several lines of evidence suggest that this deletion blocks normal splicing; most nic1 alpha-subunit mRNAs retain intron 6 and are larger and less abundant than wild-type, some nic1 alpha-subunit mRNAs are internally deleted, and wild-type alpha-subunit mRNA rescues nic1 mutant cells. The nic1 mutation reduces the size of an intron, which prevents efficient splicing of the pre-mRNA, thus blocking synthesis of the alpha-subunit and assembly of AChRs. By this route, the nic1 mutation leads to paralysis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping