The gene for soluble N-ethylmaleimide sensitive factor attachment protein α is mutated in hydrocephaly with hop gait (hyh) mice
- *Howard Hughes Medical Institute, Northwestern University, 2205 Tech Drive, Evanston, IL 60208; and †McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287
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Contributed by Joseph S. Takahashi, December 11, 2003
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 α, also known as α-SNAP, is mutated in hyh mice. α-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 α-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 α-SNAP in embryogenesis and brain development.
Footnotes
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↵ ‡ To whom correspondence should be addressed. E-mail: j-takahashi{at}northwestern.edu.
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Abbreviations: NSF, N-ethylmaleimide sensitive factor; α-SNAP, soluble NSF attachment protein α; SNAREs, SNAP receptors; SSLPs, simple sequence length polymorphisms; BAC, bacterial artificial chromosome; IP, immunoprecipitation.
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See Commentary on page 1431.
- Copyright © 2004, The National Academy of Sciences
