Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene.
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.
Probst
F J
FJ
Department of Human Genetics, 4701 MSRB III, University of Michigan, 1500 West Medical Center Drive, Ann Arbor, MI 48109, USA.
Fridell
R A
RA
Raphael
Y
Y
Saunders
T L
TL
Wang
A
A
Liang
Y
Y
Morell
R J
RJ
Touchman
J W
JW
Lyons
R H
RH
Noben-Trauth
K
K
Friedman
T B
TB
Camper
S A
SA
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
D009218:Myosins