title: Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene.
abstract: The shaker-2 mouse mutation, the homolog of human DFNB3, causes deafness and circling behavior. A bacterial artificial chromosome (BAC) transgene from the shaker-2 critical region corrected the vestibular defects, deafness, and inner ear morphology of shaker-2 mice. An unconventional myosin gene, Myo15, was discovered by DNA sequencing of this BAC. Shaker-2 mice were found to have an amino acid substitution at a highly conserved position within the motor domain of this myosin. Auditory hair cells of shaker-2 mice have very short stereocilia and a long actin-containing protrusion extending from their basal end. This histopathology suggests that Myo15 is necessary for actin organization in the hair cells of the cochlea.
authors.affiliation: Department of Human Genetics, 4701 MSRB III, University of Michigan, 1500 West Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Probst
authors.forename: R A
authors.initials: RA
authors.lastname: Fridell
authors.forename: Y
authors.initials: Y
authors.lastname: Raphael
authors.forename: T L
authors.initials: TL
authors.lastname: Saunders
authors.forename: A
authors.initials: A
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: R J
authors.initials: RJ
authors.lastname: Morell
authors.forename: J W
authors.initials: JW
authors.lastname: Touchman
authors.forename: R H
authors.initials: RH
authors.lastname: Lyons
authors.forename: K
authors.initials: K
authors.lastname: Noben-Trauth
authors.forename: T B
authors.initials: TB
authors.lastname: Friedman
authors.forename: S A
authors.initials: SA
authors.lastname: Camper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002876:Chromosomes, Bacterial; D003638:Deafness / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D007758:Ear, Inner / Q000378:metabolism; D005260:Female; D005816:Genetic Complementation Test; D006198:Hair Cells, Auditory / Q000648:ultrastructure; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009218:Myosins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D019076:Transgenes
chemical_list: D009218:Myosins