Expression of novel basement membrane components in the developing human kidney and eye

The distribution of two novel human, basement-membrane (BM) collagens has been characterized by immunohistochemical analysis of developing and mature tissue using monoclonal antibodies specific for the non-collagenous (NC1) domain of each molecule. A distribution more restricted than that of type IV collagen was observed. In the kidney, the 28K parent molecules appear relatively late, at the early capillary-loop stage of glomerular development, whereas type IV collagen is present in all BM, including those of the ureteric bud, S-form, primitive glomerulus, and vessels. Antibody to the Alport familial nephritis antigen (a 26K peptide), which is missing from epidermal BM and glomerular BM in Alport syndrome, reacted with the ureteral bud BM and all stages of glomerular BM development from the early capillary-loop stage onward, but not with BM of more primitive glomeruli (vesicles and S forms). In the human fetal eye, the collagen molecules from which the 28K NC1 peptides are derived appear later in development than type IV collagen. They are present in trace amounts in Bruch's membrane but are not detected until after birth in the retinal internal limiting membrane and cuticular and non-pigmented epithelial BM of the ciliary process. In contrast, the BM of the lens capsule and Descemet's membrane were reactive with anti-28K antibodies early in development. In all instances, the 28K peptides are detected in BM that also contain the Alport antigen, although the later is present in some BM not containing the 28K peptides. The distribution of Alport antigen and type IV collagen in developing eye is similar to that observed in the mature eye. The 28K parent molecules appear to be expressed in concert with the maturation of the BM, coincident with fusion of glomerular endothelial and epithelial BM, whereas the lens capsule BM and Descemet's membrane contain these restricted components much earlier in gestation.