Apoptosis in the lens anlage of the heritable lens aplastic mouse (lap mouse)

Adult homozygous lap mice show various eye abnormalities, such as aphakia, retinal disorganization, and dysplasia of the cornea and anterior chamber. In the fetal eye of a homozygous lap mouse, the lens placode seems to develop normally. However, the lens vesicle progresses abnormally to form a mass of cells without a cavity, and the mass vanishes soon afterward. We examined cell death in the lens anlage of this mutant. The lens anlagen of homozygous lap and normal mice from days 10 to 12 of gestation were observed by light microscopy after DNA end-labeling by immunohistochemistry and by transmission electron microscopy. By light microscopy, a slight frequency of cell death was detected in the lens anlage encircling the surface ectoderm and in the anlage or in the anlage of both homozygous lap mice and normal mice at day 10 of gestation. Cell death was seen in the lens anlage encircling the surface ectoderm in the normal mouse and sporadically in the anlage of the homozygous lap mouse at day 10.5 of gestation. Cell death was visible at the area of the lens vesicle attached to the surface ectoderm and encircling the surrounding surface ectoderm in the normal mouse, and in the lens anlage encircling the surface ectoderm and the apex areas of the lens anlage in the homozygous lap mouse at day 11 of gestation. At day 12 of gestation, almost no cell death was observed in the lens anlage of the normal mouse. However, extensive areas of cell death were still seen in the lens anlage at its apex, at the inner region, and encircling the surface ectoderm in the homozygous lap mouse. Electron microscopic observation showed that the dead cells observed in the lens anlagen by light microscopy in normal and lap mice are the result of apoptosis. In lap mice, cells with cytoplasmic condensation were observed mainly at days 10 and 10.5 of gestation. Many apoptotic bodies which had been phagocytosed by adjacent cells were seen predominantly at day 11 of gestation. At day 12 of gestation, apoptotic bodies phagocytosed by adjacent cells, which were seen at day 11, were still predominant, but there were more apoptotic bodies per cell and more digested apoptotic bodies than at day 11. These results indicate that cell death, resulting from apoptosis is involved in the disappearance of the lens anlage of lap mice.