Hypoplastic basement membrane of the lens anlage in the inheritable lens aplastic mouse (lap mouse)

Adult homozygous lap mice show various eye abnormalities such as aphakia, r etinal disorganization, and dysplasia of the cornea and anterior chamber. I n the fetal eye of a homozygous lap mouse, the lens placode appears to deve lop normally, However, the lens vesicle develops abnormally to form a mass of cells without a cavity, and the mass vanishes soon afterward. Apoptotic cell death is associated with the disappearance of the lens anlage. We exam ined the basement membranes of the lens anlage of this mutant by immunohist ochemical methods under light microscopy using antibodies against basement membrane components of the lens anlage, type IV collagen, fibronectin, lami nin, heparan sulfate proteoglycan, and entactin and by transmission electro n microscopy. Immunohistochemistry showed the distribution and intensity of antibody binding to the lens anlage to be almost the same for each these a ntibodies regardless of the stage of gestation or whether the anlagen were from normal BALB/c or lap mice. Thus, positive continuous reactions were ob served around the exterior region of the lens anlage from day 10 of gestati on for type IV collagen, fibronectin, laminin, heparan sulfate proteoglycan antibodies, and at least from day 11 of gestation for entactin antibody. T he basement membrane lamina densa of both normal and lap mice was shown by electron microscopy to be discontinuous at days 10 and 10.5 of gestation. H owever, by day 11 the lamina densa was continuous in the lens anlagen of no rmal mice but still discontinuous in the lap mice. By day 12 of gestation, the lamina densa had thickened markedly in normal mice, whereas in lap mice it remained discontinuous and its thinness indicated hypoplasia. These res ults indicate that, while all basement components examined are produced and deposited in the normal region of the lens anlage in the lap mouse, the ba sement membrane is, for some reason, imperfectly formed. The time at which hypoplasia of the basement membrane was observed in this mutant coincided w ith the stage during which apoptosis in the lens anlage occurred. This resu lt may indicate a possibility of the relationship between the basement memb rane and apoptosis in this mutant. (C) 2000 Wiley-Liss, Inc.