title: Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31.
abstract: 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.
authors.affiliation: MRC Mammalian Genetics Unit and UK Mouse Genome Centre, Harwell, Oxon OX11 ORD, UK.
authors.forename: Philomena
authors.initials: P
authors.lastname: Mburu
authors.forename: Mirna
authors.initials: M
authors.lastname: Mustapha
authors.forename: Anabel
authors.initials: A
authors.lastname: Varela
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.forename: Aziz
authors.initials: A
authors.lastname: El-Amraoui
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Holme
authors.forename: Andreas
authors.initials: A
authors.lastname: Rump
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Hardisty
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanchard
authors.forename: Roney S
authors.initials: RS
authors.lastname: Coimbra
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perfettini
authors.forename: Nick
authors.initials: N
authors.lastname: Parkinson
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Mallon
authors.forename: Pete
authors.initials: P
authors.lastname: Glenister
authors.forename: Mike J
authors.initials: MJ
authors.lastname: Rogers
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Paige
authors.forename: Lee
authors.initials: L
authors.lastname: Moir
authors.forename: Jo
authors.initials: J
authors.lastname: Clay
authors.forename: Andre
authors.initials: A
authors.lastname: Rosenthal
authors.forename: Xue Zhong
authors.initials: XZ
authors.lastname: Liu
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Blanco
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
mesh_terms: 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
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C477219:WHRN protein, human; C477218:Whrn protein, mouse