Grass D S, Felkner R H, Chiang M Y, Wallace R E, Nevalainen T J, Bennett C F, Swanson M E
DNX Transgenics, Princeton, New Jersey 08540, USA.
J Clin Invest. 1996 May 15;97(10):2233-41. doi: 10.1172/JCI118664.
Group II PLA2 has been implicated in inflammatory processes in both man and other animals and has been shown to be involved in inflammatory conditions, such as arthritis and sepsis. Transgenic mice expressing the human group II PLA2 gene have been generated using a 6.2-kb genomic fragment. These mice express the group II PLA2 gene abundantly in liver, lung, kidney, and skin, and have serum PLA2 activity levels approximately eightfold higher than nontransgenic littermates. The group II PLA2 transgenic mice reported here exhibit epidermal and adnexal hyperplasia, hyperkeratosis, and almost total alopecia. The chronic epidermal hyperplasia and hyperkeratosis seen in these mice is similar to that seen in a variety of dermatopathies, including psoriasis. However, unlike what is seen with these dermatopathies, no significant inflammatory-cell influx was observed in the skin of these animals, or in any other tissue examined. These mice provide an important tool for examining group II PLA2 expression, and for determining the role of group II PLA2 in normal and disease physiology. They serve as an in vivo model for identifying inhibitors of group II PLA2 activity and gene expression.
II 型磷脂酶 A2 已被证实与人及其他动物的炎症过程有关，并已表明它参与了诸如关节炎和败血症等炎症性疾病。利用一个 6.2 千碱基的基因组片段培育出了表达人类 II 型磷脂酶 A2 基因的转基因小鼠。这些小鼠在肝脏、肺、肾脏和皮肤中大量表达 II 型磷脂酶 A2 基因，其血清磷脂酶 A2 活性水平比非转基因同窝小鼠高约八倍。本文报道的 II 型磷脂酶 A2 转基因小鼠表现出表皮和附属器增生、角化过度以及几乎完全脱毛。这些小鼠中所见的慢性表皮增生和角化过度与包括牛皮癣在内的多种皮肤病中所见的情况相似。然而，与这些皮肤病不同的是，在这些动物的皮肤或任何其他检查的组织中均未观察到明显的炎症细胞浸润。这些小鼠为研究 II 型磷脂酶 A2 的表达以及确定 II 型磷脂酶 A2 在正常和疾病生理学中的作用提供了重要工具。它们可作为一种体内模型用于鉴定 II 型磷脂酶 A2 活性和基因表达的抑制剂。
