Dure L S, Landwehrmeyer G B, Golden J, McNeil S M, Ge P, Aizawa H, Huang Q, Ambrose C M, Duyao M P, Bird E D
Department of Neurology, Massachusetts General Hospital, Boston 02114.
Brain Res. 1994 Oct 3;659(1-2):33-41. doi: 10.1016/0006-8993(94)90860-5.
To examine the expression of the gene which causes Huntington's disease (HD), IT15, during development, in situ hybridization of radiolabeled riboprobes was performed in human fetal (gestational ages 20-23 weeks) and adult brain. Optical densities of autoradiographs were determined in various brain regions and compared to cell density in those regions. IT15 expression was found in all regions of the fetal and adult brain, and there was a high degree of correlation of autoradiographic signal with cell number in all regions but germinal matrix in fetal brain and white matter in adult brain. These two regions are notable for their significant proportion of glial cells, and suggest that IT15 expression is predominantly neuronal. There was no preponderance of IT15 expression in striatal compartments in fetal brain as demonstrated by acetylcholinesterase activity, nor was there differential expression of IT15 in brain regions known to be particularly affected in HD. IT15 gene expression is present by 20 weeks gestation in human brain, and at that stage of development exhibits a pattern of distribution which is similar to adult brain. If a developmentally-regulated role for IT15 exists in the pathogenesis of HD, it must occur prior to 20 weeks gestation.
为了研究导致亨廷顿舞蹈病（HD）的IT15基因在发育过程中的表达情况，我们在人类胎儿（孕龄20 - 23周）和成人大脑中进行了放射性标记核糖探针的原位杂交。在不同脑区测定放射自显影片的光密度，并与这些区域的细胞密度进行比较。在胎儿和成人大脑的所有区域均发现了IT15表达，除胎儿脑的生发基质和成人脑的白质外，在所有区域放射自显影信号与细胞数量之间均存在高度相关性。这两个区域以其胶质细胞的显著比例而闻名，提示IT15表达主要为神经元性。如通过乙酰胆碱酯酶活性所证实的，胎儿脑中纹状体区不存在IT15表达优势，在已知HD中特别受累的脑区也不存在IT15的差异表达。在人类大脑中，IT15基因在孕20周时就已存在表达，且在该发育阶段呈现出与成人大脑相似的分布模式。如果IT15在HD发病机制中存在发育调节作用，那么它必定发生在孕20周之前。
