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遗传性晶状体发育不全小鼠(lap小鼠)晶状体原基中的细胞凋亡。

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

作者信息

Aso S, Tashiro M, Baba R, Sawaki M, Noda S, Fujita M

机构信息

Chemicals Inspection and Testing Institute, Oita, Japan.

出版信息

Teratology. 1998 Aug;58(2):44-53. doi: 10.1002/(SICI)1096-9926(199808)58:2<44::AID-TERA5>3.0.CO;2-0.

Abstract

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.

摘要

成年纯合lap小鼠表现出各种眼部异常,如无晶状体、视网膜结构紊乱以及角膜和前房发育异常。在纯合lap小鼠的胎儿眼中,晶状体原基似乎发育正常。然而,晶状体泡异常进展,形成一团没有腔的细胞,随后这团细胞很快消失。我们研究了这种突变体晶状体原基中的细胞死亡情况。通过免疫组织化学进行DNA末端标记后,利用光学显微镜和透射电子显微镜观察了妊娠第10至12天纯合lap小鼠和正常小鼠的晶状体原基。光学显微镜观察发现,在妊娠第10天,围绕表面外胚层的晶状体原基以及纯合lap小鼠和正常小鼠的原基中均检测到轻微的细胞死亡频率。在妊娠第10.5天,正常小鼠围绕表面外胚层的晶状体原基中可见细胞死亡,纯合lap小鼠的原基中偶尔可见细胞死亡。在妊娠第11天,正常小鼠中,在与表面外胚层相连并围绕周围表面外胚层的晶状体泡区域可见细胞死亡,纯合lap小鼠中,在围绕表面外胚层的晶状体原基以及晶状体原基的顶端区域可见细胞死亡。在妊娠第12天,正常小鼠的晶状体原基中几乎未观察到细胞死亡。然而,在纯合lap小鼠中,晶状体原基的顶端、内部区域以及围绕表面外胚层的区域仍可见广泛的细胞死亡。电子显微镜观察表明,光学显微镜下在正常小鼠和lap小鼠晶状体原基中观察到的死亡细胞是凋亡的结果。在lap小鼠中,主要在妊娠第10天和第10.5天观察到具有细胞质浓缩的细胞。在妊娠第11天,主要可见许多已被相邻细胞吞噬的凋亡小体。在妊娠第12天,在第11天可见的被相邻细胞吞噬的凋亡小体仍然占主导,但每个细胞中的凋亡小体更多,且消化的凋亡小体比第11天更多。这些结果表明,凋亡导致的细胞死亡与lap小鼠晶状体原基的消失有关。

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