Distribution and lack of nidogen-1, part of numerous basement membranes, were studied in the mouse eye. For that purpose, eyes of C57BL/6 and nidogen-1 knockout mice were stained immunohistochemically for nidogen-1, and intraocular pressure measurements and light- and electron microscopy were used to study the nidogen-1 knockout animals. In normal mice, nidogen-1 was present in many basement membranes, but showed irregularities underneath the corneal epithelium, in Bruch’s membrane and in the iris. Homozygous knockout of nidogen-1 in the mouse showed only mild pathological changes. In the anterior eye segment, small interruptions were noted in the nonpigmented ciliary epithelium without further consequences. In the posterior eye segment, interruptions of the inner limiting membrane led to small retinal ectopias and subsequent changes in the optic nerve. In summary, the knockout of nidogen-1 showed mild but significant morphological changes pointing to the importance of this protein which can in part, but not completely; be replaced by nidogen-2. 1. Introduction Basement membranes form the natural supporting structure upon which cells migrate, proliferate, and differentiate. They contain a tissue-specific composition of extracellular matrix components, containing collagen type IV, laminin, heparan sulfate proteoglycans, and nidogen. In mammals the nidogen family consists of two members, nidogen 1 and 2. Both isoforms bind to a wide spectrum of BM-associated proteins, and it has been proposed that they act as connecting elements between the laminin and collagen IV networks [1–4]. Nidogen-1-deficient animals show only mild phenotypes [5–7]; most BMs are ultrastructurally normal, and there is little change in cellular or tissue morphology. The homozygous knockout animals are generally healthy, have a normal lifespan, and are fertile. Specific settings reveal mild neurological abnormalities in these animals [5, 8]. Nidogen-2-deficient animals show no primary phenotype, but are more sensitive to pathologies like hypertension [9] and cancer [10–12]. Double mutants lacking both isoforms die shortly after birth with abnormalities directly related to defects in BM assembly [13, 14]. In the eye, nidogen-1 is described to be present in numerous basement membranes. Studies in the mouse are, however, restricted to the cornea and retina [15, 16]. The aim of this study was to investigate the distribution of nidogen in the normal adult murine eye and to describe the phenotype after nidogen-1 knockout. In our primary hypothesis, we suspected a link between basement
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