COMPARATIVE DISTRIBUTION OF THE ALPHA-1(IV), ALPHA-5(IV), AND ALPHA-6(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 alpha 5 (IV) and alpha 6(IV) collagen chains lie head-to-head on Xq22 and are deleted in patients with Alport syndrome (AS)-associated diffuse leiom yomatosis. In this study, we raised a rabbit anti-human alpha 6(IV) ch ain antibody, demonstrated its specificity by the analysis of recombin ant NC1 domains of all six type IV chains, and studied the distributio n of the alpha 6(IV) chain in relation to the alpha 1(IV) and (alpha 5 (IV) chains in human adult and fetal tissues involved in AS and diffus e leiomyomatosis. The alpha 6(IV) chain colocalizes with the alpha 5(I V) chain in basement membranes (BMs) of many tissues, but not in glome rular BM. These data exclude the alpha 6(IV) chain as a site for AS mu tations. The head-to-head genomic pairing of the (alpha 5(IV) and alph a 6(IV) genes implies coordinate transcription of the two genes. Diffe rential localization of the alpha 5(TV) and (alpha 6(IV) chains shows that the two chains are not always coordinately regulated. The alpha 6 (IV) chain, together with the alpha 3(IV)-alpha 5(IV) chains, was abse nt from all renal BMs in eight patients with X-linked AS while the alp ha 1(IV) and alpha 2(IV) chains were increased. The data support the e xistence of two independent collagen networks, one for the alpha 3(IV) -alpha 6(IV) chains and one for the alpha 1(IV) and alpha 2(IV) chains .