Dystroglycan expression in the mouse cochlea

Abstract

Viable dominant spotting (W v/W v) mice have a c-kit gene mutation, which impedes the migration of neural crest cells to the developing cochlea where they normally differentiate into intermediate cells (ICs). A prominent pathological feature shared by these mutants and the aging human and gerbil cochlea is thickening of the basement membrane (BM) of strial capillaries. Atrophy of strial capillaries in the aging gerbil has been associated with changes in the expression of dystroglycan (DG), a cell-surface receptor that regulates BM assembly. Here we evaluated the expression of DG in W v/W v mutant and C57BL/6J wild-type mice to investigate the possible role of ICs in regulating strial capillary BM homeostasis. The DG gene product was identified in lateral wall dissections from both W v/W v mutant and wild-type mice by reverse transcription-polymerase chain reaction. Subunit-specific antibodies were employed to localize the α and β subunits of the DG heterodimer. Some sites in both wild-type and mutant mice, such as the subepithelial BM lining the scala media and regions of contact between selected epithelial cells, expressed α-DG alone. Other sites such as the perineural BM and the perivascular BM subtending strial capillaries and capillaries in the central portion of the auditory nerve coexpressed α- and β-DG. The strong diffuse staining for α-DG along the basolateral membrane of strial marginal cells disappeared with advancing strial degeneration in abnormal turns of W v/W v mutants. Variations in staining intensity for both α- and β-DG also occurred in the subendothelial BM of strial capillaries in turns lacking ICs and appeared to correspond with the degree of capillary atrophy. The results support the possibility that ICs play a role in the homeostasis of the strial capillary BM.