Abstract. Laminin and collagen IV are components of most basal laminae (BLs). Recently, both have been shown to be products of multigene families. The A, B1, and B2 subunits of the laminin trimer are products of related genes, and the BL components merosin M and s-laminin are homologues of the A and B1 subunits, respectively. Similarly, five related collagen IV chains, al(IV)-ct5(IV), have been described. Here, we used a panel of subunit-specific antibodies to determine the distribution of the laminin and collagen IV isoforms in adult BLs. First, we compared synaptic and extrasynaptic portions of muscle fiber BL, in light of evidence that axonal and muscle membranes interact selectively with synaptic BL during neuromuscular regeneration. S-laminin, laminin A, and collagens oL3(IV) and o~4(IV) are greatly concentrated in synaptic BL; laminin B1 is apparently absent from synaptic BL; collagens od(IV) and o~2(IV) are less abundant in synaptic than extrasynaptic BL; and laminin B2 and merosin M are present at similar levels synaptically and extrasynaptically. These results reveal widespread differences between synaptic and extrasynaptic BL, and implicate several novel polypeptides as candidate mediators of neuromuscular interactions. Second, we widened our inquiry to assess the composition of several other BLs: endoneurial and perineurial BLs in intramuscular nerves, BLs associated with intramuscular vasculature, and glomerular and tubular BLs in kidney. Of eight BLs studied, at least seven have distinct compositions, and of the nine BL components tested, at least seven have distinct distributions. These results demonstrate a hitherto undescribed degree of heterogeneity among BLs. BASAL laminae (BLs)' throughout the vertebrate body are thought to contain a number of common components-notably laminin, collagen IV, nidogen/entactin, and a heparan sulfate proteoglycan (reviewed in Timpl and Dziadzek, 1986;Martin and Timpl, 1987;Timpl, 1989;Inoue, 1989). These molecules are important for maintaining the structural integrity of BLs, and for mediating their attachment to other components of the extracellular matrix and to cell membranes. In addition, however, there is evidence for the existence of molecular differences among BLs, at least some of which are presumably related to tissuespecific roles that BLs play. While initial molecular analyses of BLs quite naturally focussed on their major and common constituents, recent studies have increasingly sought less abundant, tissue-specific components.We have been interested in regional specializations of the BL that ensheathes skeletal muscle fibers. Approximately D. Hunter's present address is

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Vascular and parenchymal basement membranes (BMs) are thickened in diabetes, but alterations in individual BM components in diabetic eyes, especially in diabetic retinopathy (DR), are obscure. To identify abnormalities in the distribution of specific constituents, we analyzed cryostat sections of human eyes obtained at autopsy (seven normal, five diabetic without DR, and 13 diabetic with DR) by immunofluorescence with antibodies to 30 BM and extracellular matrix components. In non-DR eyes, no qualitative changes of ocular BM components were seen. In some DR corneas, epithelial BM was stained discontinuously for laminin-1, entactin/nidogen, and alpha3-alpha4 Type IV collagen, in contrast to non-DR corneas. Major BM alterations were found in DR retinas compared to normals and non-DR diabetics. The inner limiting membrane (retinal BM) of DR eyes had accumulations of fibronectin (including cellular) and Types I, III, IV (alpha1-alpha2), and V collagen. The BM zone of new retinal blood vessels in neovascularized areas accumulated tenascin and Type XII collagen, whereas normal, diabetic, and adjacent DR retinas showed only weak and irregular staining. In preretinal membranes, perlecan, bamacan, and Types VI, VIII, XII, and XIV collagen were newly identified. Diabetic BM thickening appears to involve qualitative alterations of specific BM markers at an advanced disease stage, with the appearance of DR.