Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31.
The whirler mouse mutant (wi) does not respond to sound stimuli, and detailed ultrastructural analysis of sensory hair cells in the organ of Corti of the inner ear indicates that the whirler gene encodes a protein involved in the elongation and maintenance of stereocilia in both inner hair cells (IHCs) and outer hair cells (OHCs). BAC-mediated transgene correction of the mouse phenotype and mutation analysis identified the causative gene as encoding a novel PDZ protein called whirlin. The gene encoding whirlin also underlies the human autosomal recessive deafness locus DFNB31. In the mouse cochlea, whirlin is expressed in the sensory IHC and OHC stereocilia. Our findings suggest that this novel PDZ domain-containing molecule acts as an organizer of submembranous molecular complexes that control the coordinated actin polymerization and membrane growth of stereocilia.
Mburu
Philomena
P
MRC Mammalian Genetics Unit and UK Mouse Genome Centre, Harwell, Oxon OX11 ORD, UK.
Mustapha
Mirna
M
Varela
Anabel
A
Weil
Dominique
D
El-Amraoui
Aziz
A
Holme
Ralph H
RH
Rump
Andreas
A
Hardisty
Rachel E
RE
Blanchard
Stéphane
S
Coimbra
Roney S
RS
Perfettini
Isabelle
I
Parkinson
Nick
N
Mallon
Ann-Marie
AM
Glenister
Pete
P
Rogers
Mike J
MJ
Paige
Adam J
AJ
Moir
Lee
L
Clay
Jo
J
Rosenthal
Andre
A
Liu
Xue Zhong
XZ
Blanco
Gonzalo
G
Steel
Karen P
KP
Petit
Christine
C
Brown
Steve D M
SD
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002923:Cilia / Q000502:physiology / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D015870:Gene Expression; D005808:Genes, Recessive; D006199:Hair Cells, Auditory, Inner / Q000648:ultrastructure; D018072:Hair Cells, Auditory, Outer / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D018076:DNA, Complementary; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C477219:WHRN protein, human; C477218:Whrn protein, mouse