Comparative distribution of the α1 (IV), α5(IV), and α6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients

We have shown previously that the 5' ends of the genes for the α5 (IV) and α6 (IV) collagen chains lie head-to-head on Xq22 and are deleted in patients with Alport syndrome (AS)-associated diffuse leiomyomatosis. In this study, we raised a rabbit anti-human α6 (IV) chain antibody, demonstrated its specificity by the analysis of recombinant NC1 domains of all six type IV chains, and studied the distribution of the α6(IV) chain in relation to the α1(IV) and α5 (IV) chains in human adult and fetal tissues involved in AS and diffuse leiomyomatosis. The α6(IV) chain colocalizes with the α5(IV) chain in basement membranes (BMs) of many tissues, but not in glomerular BM. These data exclude the α6(IV) chain as a site for AS mutations. The head- to-head genomic pairing of the α5(IV) and α6(IV) genes implies coordinate transcription of the two genes. Differential localization of the α5(IV) and α6(IV) chains shows that the two chains are not always coordinately regulated. The α6 (IV) chain, together with the α3 (IV)-α5 (IV) chains, was absent from all renal BMs in eight patients with X-linked AS while the α1 (IV) and α2 (IV) chains were increased. The data support the existence of two independent collagen networks, one for the α3(IV)-α6(IV) chains and one for the α1(IV) and α2(IV) chains.