Dystroglycan expression in the developing and senescent gerbil cochlea.
Dystroglycan (DG) forms part of a cell surface laminin receptor complex and is believed to play a critical role in the assembly and homeostasis of basement membranes (BM). The receptor complex is made up of alpha- and beta-DG subunits and is found in muscle, epithelial and nerve tissue. In the cochlea, DG may be involved in the abnormal accumulation of laminin seen in the thickened BM of strial capillaries with age. This excess deposition of laminin is thought to lead to capillary necrosis and contribute to degeneration of the stria vascularis (SV). Here we assessed the presence and distribution of DG in the developing, mature and senescent gerbil cochlea in order to ascertain whether altered patterns of expression are a factor in age-related pathology. Western blots of proteins isolated from the entire cochlea demonstrated the presence of the alpha-DG subunit. mRNA encoding DG was identified in microdissected specimens of the lateral wall and the combined organ of Corti/modiolus by RT-PCR analysis. Immunohistochemical experiments localized alpha-DG in epithelial BMs and regions of epithelial cell-cell contact with no intervening BM in the developing and mature cochlea. Immunoreactive alpha-DG was present in the BM underlying strial capillaries and in vessels of the central portion of the auditory nerve, but was not detected in any other vessels in the cochlea. Age-related changes in alpha-DG expression were observed only in the SV where a marked decrease in alpha-DG immunoreactivity was seen in the BM of strial capillaries as well as throughout the SV. The results demonstrate the selective expression of alpha-DG in both BM and non-BM sites in the mature cochlea and suggests its involvement in both developmental and aging processes.
Heaney
Denise LaMarche
DL
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA. lamache@musc.edu
Schulte
Bradley A
BA
Niedzielski
Andrew S
AS
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D003051:Cochlea / Q000254:growth & development* / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D049030:Dystroglycans; D005849:Gerbillinae / Q000254:growth & development* / Q000378:metabolism*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D049030:Dystroglycans