PMID- 10369265
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20131121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 2
DP  - 1999 Jun
TI  - Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl
      co-transporter.
PG  - 192-5
AB  - Deafness can result from a variety of gene defects. Some genes involved in the
      physiology of hearing encode membrane transporters that regulate the ionic
      composition of the fluid bathing the inner ear. The endolymph is an extracellular
      fluid with an atypical composition that resembles the intracellular milieu, high 
      in K+ and low in Na+. Recent studies have emphasized the prominent role of K+
      channels in endolymph secretion and mechanical transduction. Coupled
      electroneutral transport of Na+, K+ and Cl- is mediated by two isoforms of the
      Na-K-2Cl co-transporter: the absorptive isoform BSC1 (also called NKCC2, encoded 
      by Slc12a1 in mouse) that is exclusively expressed in kidney; and BSC2/NKCC1
      (encoded by Slc12a2 in mouse), the secretory isoform which has a wider pattern of
      expression including epithelia, muscle cells, neurons and red blood cells. These 
      co-transporters share 57% homology at the amino acid level and are
      pharmacologically inhibited by loop diuretics. There is functional and
      histochemical evidence for the presence of the secretory isoform of the Na-K-2Cl 
      co-transporter in gerbil, rat and rabbit inner ear. We disrupted mouse Slc12a2
      and report here that Slc12a2-/- mice are deaf and exhibit classic shaker/waltzer 
      behaviour, indicative of inner-ear defects. We localized the co-transporter to
      key secreting epithelia of the mouse inner ear and show that absence of
      functional co-transporter leads to structural damages in the inner ear consistent
      with a decrease in endolymph secretion.
FAU - Delpire, E
AU  - Delpire E
AD  - Anesthesiology Research Division, Laboratories of Cellular & Molecular
      Physiology, and Center for Molecular Neuroscience, Vanderbilt University Medical 
      Center, Nashville, Tennessee 37232, USA. eric.delpire@mcmail.vanderbilt.edu
FAU - Lu, J
AU  - Lu J
FAU - England, R
AU  - England R
FAU - Dull, C
AU  - Dull C
FAU - Thorne, T
AU  - Thorne T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Carrier Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 0Y2S3XUQ5H (Bumetanide)
RN  - 9NEZ333N27 (Sodium)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Bumetanide/pharmacology
MH  - Carrier Proteins/*genetics/*metabolism
MH  - Cochlea/*pathology
MH  - Deafness/*genetics/pathology/physiopathology
MH  - Erythrocytes/metabolism
MH  - Hair Cells, Auditory, Outer/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Neurologic Mutants
MH  - Motor Activity
MH  - Movement Disorders/*genetics/pathology/physiopathology
MH  - Organ of Corti/*pathology
MH  - Potassium/metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - Rabbits
MH  - Rats
MH  - Restriction Mapping
MH  - Sodium/metabolism
MH  - Sodium-Potassium-Chloride Symporters
EDAT- 1999/06/16 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/16 10:00
PHST- 1999/06/16 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/16 10:00 [entrez]
AID - 10.1038/9713 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jun;22(2):192-5. doi: 10.1038/9713.