Mutation of the Na-K-Cl co-transporter gene Slc12a2 results in deafness in mice.
Hearing impairment is a common human condition, but we know little about the molecular basis of cochlear function. Shaker-with-syndactylism (sy) is a classic deaf mouse mutant and we show here that a second allele, sy(ns), is associated with abnormal production of endolymph, the fluid bathing sensory hair cells. Using a positional candidate approach, we demonstrate that mutations in the gene encoding the basolateral Na-K-Cl co-transporter Slc12a2 (Nkcc1, mBSC2) cause the deafness observed in sy and sy(ns) mice. This finding provides the molecular basis of another link in the chain of K+recycling in the cochlea, a process essential for normal cochlear function.
School of Biological Sciences and Department of Dental Medicine and Surgery, 3.239 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
M J
MJ
Dixon
J
J
Gazzard
S S
SS
Chaudhry
N
N
Sampson
B A
BA
Schulte
K P
KP
Steel
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D002874:Chromosome Mapping; D003051:Cochlea / Q000737:chemistry / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005796:Genes / Q000235:genetics; D007150:Immunohistochemistry; D017880:Limb Deformities, Congenital / Q000235:genetics; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009154:Mutation; D028021:Sodium-Potassium-Chloride Symporters; D013576:Syndactyly / Q000235:genetics
D002352:Carrier Proteins; D028021:Sodium-Potassium-Chloride Symporters; D004247:DNA