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

Abstract

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.

Type IV Procollagen Missense Mutations Associated With Defects of the Eye, Vascular Stability, the Brain, Kidney Function and Embryonic or Postnatal Viability in the Mouse, Mus musculus: An Extension of the Col4a1 Allelic Series and the Identification of the First Two Col4a2 Mutant Alleles

“…The mutations were associated with abnormalities of the lens, the cornea, vascular stability, the brain, kidney function, and survival in the embryonic or the postnatal period. These observations are consistent with the ubiquitous expression of the Col4a1 and Col4a2 genes, with specific expression documented in the cornea, the lens, the lens capsule, and the retina (Kleppel and Michael 1990;Sarthy 1993;Cheong et al 1994;Qin et al 1997;Kelley et al 2002); capillaries (Bell et al 2001;Tilling et al 2002;Urabe et al 2002); the brain (Kleppel et al 1989;Pö schl et al 2004); the kidney (Desjardins et al 1990;Gunwar et al 1998;Boutaud et al 2000); and the embryonic membrane, Reichert's membrane, and the placenta (Kleppel et al 1989;Miner et al 2004;Pö schl et al 2004). The nine Col4a1 mutations extend the mouse allelic series as well as the five COL4A1 missense mutations in humans.…”

Isoform switching of type IV collagen is developmentally arrested in X-linked Alport syndrome leading to increased susceptibility of renal basement membranes to endoproteolysis.

“…This observation seems to be species-independent, and the notion that specialized basement membranes in XAS are in developmental arrest, in retrospect, can be partially inferred from earlier work (48) and established by ours. Several recent antibody staining experiments, for example, have shown that the type IV collagen in normal GBM is represented almost exclusively by ␣3(IV), ␣4(IV), and ␣5(IV) chains (5,47,49).…”

Localization of basement membrane-associated protein isoforms during development of the ocular surface of mouse eye

“…Although many studies have analyzed the expression of extracellular matrix molecules, cytokines, integrins, and adhesion proteins in the developing eye (Cintron et al, 1984;Ben-Zvi et al, 1986;Kohno et al, 1987;Fayein et al, 1990;Kleppel and Michael, 1990;Stepp et al, 1990;Dong and Chung, 1991;Stepp, 1995), none have correlated the expression of these molecules to the differentiation sequence of ocular surface epithelial cells.…”