Messing A, Head M W, Galles K, Galbreath E J, Goldman J E, Brenner M
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 53706, USA.
Am J Pathol. 1998 Feb;152(2):391-8.
Increased expression of glial fibrillary acidic protein (GFAP) is a hallmark of gliosis, the astrocytic hypertrophy that occurs during a wide variety of diseases of the central nervous system. To determine whether this increase in GFAP expression per se alters astrocyte function, we generated transgenic mice that carry copies of the human GFAP gene driven by its own promoter. Astrocytes of these mice are hypertrophic, up-regulate small heat-shock proteins, and contain inclusion bodies identical histologically and antigenically to the Rosenthal fibers of Alexander's disease. Mice in the highest expressing lines die by the second postnatal week. The results support the notion that Alexander's disease is a disorder of astrocytes, and provide an animal model for studying the causes and consequences of inclusion body disease.
胶质纤维酸性蛋白（GFAP）表达增加是胶质增生的一个标志，胶质增生是在多种中枢神经系统疾病期间发生的星形胶质细胞肥大。为了确定GFAP表达的这种增加本身是否会改变星形胶质细胞的功能，我们构建了携带由其自身启动子驱动的人类GFAP基因拷贝的转基因小鼠。这些小鼠的星形胶质细胞肥大，上调小热休克蛋白，并含有在组织学和抗原性上与亚历山大病的罗森塔尔纤维相同的包涵体。最高表达系的小鼠在出生后第二周死亡。这些结果支持亚历山大病是一种星形胶质细胞疾病的观点，并为研究包涵体疾病的病因和后果提供了一个动物模型。
