Spatiotemporal loss of K+ transport proteins in the developing cochlear lateral wall of guinea pigs with hereditary deafness

Authors

  • Zhe Jin,

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    • *

      Present address: Lund University, Department of Clinical Sciences, Malmö, CRC, Bldg. 91, Fl. 11, Entrance 72, UMAS, SE-205 02 Malmö, Sweden.

  • Mats Ulfendahl,

    1. Center for Hearing and Communication Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Department of Otolaryngology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
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  • Leif Järlebark

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    • Present address: The Swedish Research Council – Medicine, SE-103 78 Stockholm, Sweden.


Dr Zhe Jin and Dr Leif Järlebark, Center for Hearing and Communication Research, M1:00, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
E-mail: zhe.jin@med.lu.se and leif.jarlebark@vr.se

Abstract

Genetic deafness is one of the most common human genetic birth defects. To understand the molecular mechanisms underlying human hereditary deafness, deaf animal strains have proved to be invaluable models. The German waltzing guinea pig is a new strain of animals with unidentified gene mutation(s), displaying recessively inherited cochleovestibular impairment. Histological investigations of the homozygous animals (gw/gw) revealed a collapse of the endolymphatic compartment and malformation of stria vascularis. RT-PCR showed a significant reduction in expression of the strial intermediate cell-specific gene Dct and the tight-junction gene Cldn11 in the embryonic day (E)40 and adult gw/gw cochlear lateral wall. Immunohistochemical analysis of the gw/gw cochlea showed loss of the tight junction protein CLDN11 in strial basal cells from E40, loss of the potassium channel subunit KCNJ10 in strial intermediate cells from E50, and loss of the Na–K–Cl cotransporter SLC12A2 in strial marginal cells from E50. In addition, a temporary loss of the gap junction protein GJB2 (connexin 26) between fibrocytes in the spiral ligament of the E50 gw/gw cochlea was observed. The barrier composed of tight junctions between strial basal cells was disrupted in the gw/gw cochlea as indicated by a biotin tracer permeability assay. In conclusion, spatiotemporal loss of K+ transport proteins in the cochlear lateral wall is caused by malformation of the stria vascularis in the developing German waltzing guinea pig inner ear. This new animal strain may serve as a good model for studying human genetic deafness due to disruption of inner ear ion homeostasis.

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