Expression of type IV collagen α3 and α4 chain mRNA in X-linked Alport syndrome

Abstract

X-Linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the Type IV collagen α5 chain (α5(IV)). The authors' recent immunohistochemical study demonstrated abnormal expression of α3(IV) and α4(IV), as well as of α5(IV), in patients with this syndrome, and a correlation between abnormal α3(IV) and α4(IV) expression and severity of the disease. The mechanism linking α5(IV) mutations with abnormal α3(IV) and α4(IV) expression is unknown. To examine α3(IV) and α4(IV) mRNA expression in renal cortical tissues of patients with X-linked Alport syndrome, a nonradioisotopic, semiquantitative reverse transcription- polymerase chain reaction assay (α3(IV) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α4(IV), and GAPDH coamplification) was performed. There were no significant differences among severely affected male (N = 3), mildly affected male (N = 2), and female (N = 1) X-linked Alport patients and control subjects (N = 2) with respect to α3(IV) and α4(IV) mRNA expression in renal cortical tissue. These findings indicate that α3(IV) and α4(IV) transcription is not turned off in X-linked Alport syndrome and suggest that abnormal expression of α3(IV) and α4(IV) proteins in this syndrome may be the result of failure of incorporation of α3(IV) and α4(IV) into the glomerular basement membrane.