Matilla A, Roberson E D, Banfi S, Morales J, Armstrong D L, Burright E N, Orr H T, Sweatt J D, Zoghbi H Y, Matzuk M M
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurosci. 1998 Jul 15;18(14):5508-16. doi: 10.1523/JNEUROSCI.18-14-05508.1998.
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. To investigate SCA1 pathogenesis and to gain insight into the function of the SCA1 gene product ataxin-1, a novel protein without homology to previously described proteins, we generated mice with a targeted deletion in the murine Sca1 gene. Mice lacking ataxin-1 are viable, fertile, and do not show any evidence of ataxia or neurodegeneration. However, Sca1 null mice demonstrate decreased exploratory behavior, pronounced deficits in the spatial version of the Morris water maze test, and impaired performance on the rotating rod apparatus. Furthermore, neurophysiological studies performed in area CA1 of the hippocampus reveal decreased paired-pulse facilitation in Sca1 null mice, whereas long-term and post-tetanic potentiations are normal. These findings demonstrate that SCA1 is not caused by loss of function of ataxin-1 and point to the possible role of ataxin-1 in learning and memory.
1型脊髓小脑共济失调（SCA1）是一种神经退行性疾病，其特征为共济失调、进行性运动功能衰退以及小脑浦肯野细胞丢失。为了研究SCA1的发病机制，并深入了解SCA1基因产物ataxin-1（一种与先前描述的蛋白质无同源性的新型蛋白质）的功能，我们构建了在小鼠Sca1基因中存在靶向缺失的小鼠。缺乏ataxin-1的小鼠能够存活、繁殖，且未表现出任何共济失调或神经退行性变的迹象。然而，Sca1基因敲除小鼠表现出探索行为减少、在莫里斯水迷宫试验的空间版本中存在明显缺陷以及在转棒试验中的表现受损。此外，在海马体CA1区进行的神经生理学研究显示，Sca1基因敲除小鼠的双脉冲易化作用减弱，而长时程增强和强直后增强则正常。这些发现表明，SCA1并非由ataxin-1功能丧失所致，并提示ataxin-1在学习和记忆中可能发挥的作用。
