title: The gene for soluble N-ethylmaleimide sensitive factor attachment protein alpha is mutated in hydrocephaly with hop gait (hyh) mice.
abstract: The spontaneous autosomal recessive mouse mutant for hydrocephaly with hop gait (hyh) exhibits dramatic cystic dilation of the ventricles at birth and invariably develops hopping gait. We show that the gene for soluble N-ethylmaleimide sensitive factor attachment protein alpha, also known as alpha-SNAP, is mutated in hyh mice. alpha-SNAP plays a key role in a wide variety of membrane fusion events in eukaryotic cells, including the regulated exocytosis of neurotransmitters. Homozygous mutant mice harbor a missense mutation M105I in a conserved residue in one of the alpha-helical domains. We demonstrate that the hyh mutant is not a null allele and is expressed; however, the mutant protein is 40% less abundant in hyh mice. The hyh mutant provides a valuable in vivo model to study vesicle/membrane trafficking and provides insight into the potential roles of alpha-SNAP in embryogenesis and brain development.
authors.affiliation: Howard Hughes Medical Institute, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA.
authors.forename: Hee-Kyung
authors.initials: HK
authors.lastname: Hong
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D005684:Gait / Q000235:genetics*; D006849:Hydrocephalus / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins