COLLAGEN-IV ALPHA-3-CHAIN, ALPHA-4-CHAIN, AND ALPHA-5-CHAIN IN RODENTBASAL LAMINAE - SEQUENCE, DISTRIBUTION, ASSOCIATION WITH LAMININS, AND DEVELOPMENTAL SWITCHES

Collagen IV is a major component of vertebrate basal laminae (BLs). St udies in humans have revealed a family of genes encoding alpha 1-alpha 6 collagen IV chains and implicated alpha 3-alpha 6 in disease proces ses (Goodpasture and Alport syndromes and diffuse leiomyomatosis). To extend studies of these components to an experimentally accessible ani mal, we cloned cDNAs encoding partial collagen alpha 3, alpha 4, and a lpha 5(IV) chains from the mouse. Ribonuclease protection assays showe d that all three genes were expressed at highest levels in kidney and lung; alpha 5(IV) was also expressed at high levels in heart. We then made antibodies specific for each collagen IV chain. Immunohistochemic al studies of several tissues revealed many combinations of collagen I V chains; however, alpha 3 and alpha 4 (IV) were always coexpressed, a nd only appeared in BLs that were alpha 5(IV) positive. The alpha 3-al pha 5(IV) chains were frequently but not exclusively associated with t he S (beta 2) chain of laminin, as were the alpha 1, 2 (IV) collagen c hains with laminin B1 (beta 1). An analysis of developing rat kidney B Ls showed that newly formed (S-shaped) nephrons harbored collagen arl and alpha 2(IV) and laminin B1; maturing (capillary loop stage) BLs co ntained collagen alpha 1-alpha 5(IV) and laminin B1 and S-laminin; and mature glomerular BLs contained mainly collagen alpha 3-alpha 5(TV) a nd S-laminin. Thus, collagen alpha 1 and alpha 2(TV) and laminin B1 ap pear to be fetal components of the glomerular BL, and there is a devel opmental switch to collagen alpha 3-alpha 5(IV) and S-laminin expressi on.