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Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter.
Nat Genet. 1999 Jun; 22(2):192-5.NGen

Abstract

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.

Authors+Show Affiliations

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.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10369265

Citation

Delpire, E, et al. "Deafness and Imbalance Associated With Inactivation of the Secretory Na-K-2Cl Co-transporter." Nature Genetics, vol. 22, no. 2, 1999, pp. 192-5.
Delpire E, Lu J, England R, et al. Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter. Nat Genet. 1999;22(2):192-5.
Delpire, E., Lu, J., England, R., Dull, C., & Thorne, T. (1999). Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter. Nature Genetics, 22(2), 192-5.
Delpire E, et al. Deafness and Imbalance Associated With Inactivation of the Secretory Na-K-2Cl Co-transporter. Nat Genet. 1999;22(2):192-5. PubMed PMID: 10369265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter. AU - Delpire,E, AU - Lu,J, AU - England,R, AU - Dull,C, AU - Thorne,T, PY - 1999/6/16/pubmed PY - 2001/3/23/medline PY - 1999/6/16/entrez SP - 192 EP - 5 JF - Nature genetics JO - Nat. Genet. VL - 22 IS - 2 N2 - 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. SN - 1061-4036 UR - https://www.unboundmedicine.com/medline/citation/10369265/Deafness_and_imbalance_associated_with_inactivation_of_the_secretory_Na_K_2Cl_co_transporter_ L2 - http://dx.doi.org/10.1038/9713 DB - PRIME DP - Unbound Medicine ER -