Collagen IV is a major component of vertebrate basal laminae (BLs). Studies in humans have revealed a family of genes encoding alpha 1-alpha 6
collagen IV chains and implicated alpha 3-alpha 6 in disease processes (Goodpasture and Alport syndromes and diffuse
leiomyomatosis). To extend studies of these components to an experimentally accessible animal, we cloned cDNAs encoding partial
collagen alpha 3, alpha 4, and alpha 5(IV) chains from the mouse.
Ribonuclease protection assays showed 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. Immunohistochemical studies of several tissues revealed many combinations of
collagen IV chains; however, alpha 3 and alpha 4 (IV) were always coexpressed, and only appeared in BLs that were alpha 5(IV) positive. The alpha 3-alpha 5(IV) chains were frequently but not exclusively associated with the S (beta 2) chain of
laminin, as were the alpha 1, 2 (IV)
collagen chains with
laminin B1 (beta 1). An analysis of developing rat kidney BLs showed that newly formed (S-shaped) nephrons harbored
collagen alpha 1 and alpha 2(IV) and
laminin B1; maturing (capillary loop stage) BLs contained
collagen alpha 1-alpha 5(IV) and
laminin B1 and
S-laminin; and mature glomerular BLs contained mainly
collagen alpha 3-alpha 5(IV) and
S-laminin. Thus,
collagen alpha 1 and alpha 2(IV) and
laminin B1 appear to be fetal components of the glomerular BL, and there is a developmental switch to
collagen alpha 3-alpha 5(IV) and
S-laminin expression.