Present address: Lund University, Department of Clinical Sciences, Malmö, CRC, Bldg. 91, Fl. 11, Entrance 72, UMAS, SE-205 02 Malmö, Sweden.
Spatiotemporal loss of K+ transport proteins in the developing cochlear lateral wall of guinea pigs with hereditary deafness
Article first published online: 17 DEC 2007
European Journal of Neuroscience
Volume 27, Issue 1, pages 145–154, January 2008
How to Cite
Jin, Z., Ulfendahl, M. and Järlebark, L. (2008), Spatiotemporal loss of K+ transport proteins in the developing cochlear lateral wall of guinea pigs with hereditary deafness. European Journal of Neuroscience, 27: 145–154. doi: 10.1111/j.1460-9568.2007.05994.x
- Issue published online: 20 DEC 2007
- Article first published online: 17 DEC 2007
- Received 2 April 2007, revised 30 October 2007, accepted 15 November 2007
- embryonic development;
- stria vascularis
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.