Tamura H, Jidoi J, Naora H, Matsui H, Katsuki M, Tanaka O
Department of Dermatology, Shimane Medical University, Izumo, Japan.
Invest Ophthalmol Vis Sci. 1995 Feb;36(2):467-77.
During the generation of transgenic mice (TGs) introduced with mouse T-cell receptor delta (TCR delta) gene, the authors found a TG line with corneal opacity that coincided with the presence of the transgene. The authors investigated the pathogenesis and molecular mechanisms of this corneal opacity in this line.
The pathologic features and pathogenesis of the corneal opacity in TGs were examined histologically using transmission and scanning electron microscopy, as well as light microscopy. DNA and RNA blot analyses were performed to examine the copy number and the expression of the transgenes, respectively.
Histologically, edema of the corneal epithelium and adhesion of the iris to the cornea were observed in adult TGs. In the developmental analysis, the authors first observed relative hypoplasia of the ciliary body on day 18 of gestation and dysgenesis of the anterior chamber angle from postnatal day 2. Corneal opacity was observed from postnatal day 8, coinciding with the histologic vesicular change of the epithelium. No inflammation was observed through its life. In the sublines that have different copy numbers of the transgene, the occurrence of the opacity depended on the copy number of the transgene. Expression of the transgene in the thymus was consistent with the number of the introduced transgene.
In a TCR delta TG line, the overexpression of transgenes coincided with abnormal development of the ocular anterior segment and the corneal opacity. Pathogenesis is described, and possible molecular mechanisms are discussed.
在导入小鼠T细胞受体δ（TCRδ）基因的转基因小鼠（TGs）培育过程中，作者发现了一个角膜混浊的TG品系，且该混浊与转基因的存在一致。作者对该品系中这种角膜混浊的发病机制和分子机制进行了研究。
使用透射电子显微镜、扫描电子显微镜以及光学显微镜，从组织学角度检查TGs角膜混浊的病理特征和发病机制。分别进行DNA印迹分析和RNA印迹分析，以检测转基因的拷贝数和表达情况。
组织学检查发现，成年TGs存在角膜上皮水肿以及虹膜与角膜粘连的情况。在发育分析中，作者在妊娠第18天首次观察到睫状体相对发育不全，出生后第2天观察到前房角发育异常。出生后第8天观察到角膜混浊，同时上皮出现组织学水泡样改变。在其整个生命周期内均未观察到炎症。在转基因拷贝数不同的亚系中，混浊的发生取决于转基因的拷贝数。转基因在胸腺中的表达与导入的转基因数量一致。
在一个TCRδ TG品系中，转基因的过度表达与眼前节异常发育和角膜混浊同时出现。本文描述了发病机制，并讨论了可能的分子机制。
