Li S H, Schilling G, Young W S, Li X J, Margolis R L, Stine O C, Wagster M V, Abbott M H, Franz M L, Ranen N G
Laboratory of Molecular Neurobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196.
Neuron. 1993 Nov;11(5):985-93. doi: 10.1016/0896-6273(93)90127-d.
Huntington's Disease (HD) is notable for selective neuronal vulnerability in the basal ganglia and cerebral cortex. We have investigated in human and rodent tissues the expression of the gene (IT15) whose mutation causes HD. IT15 is widely expressed, with highest levels of expression in brain, but also in lung, testis, ovary, and other tissues. Within the brain, expression is widespread with a neuronal pattern and is not enriched in the basal ganglia. Expression of IT15 is not reduced in the brain of HD patients when corrected for actin (though it is slightly decreased in the striatum when uncorrected, consistent with neuronal loss). Thus, the widespread distribution of IT15 expression does not correspond with the restricted distribution of neuropathologic changes in HD. We suggest that pathophysiology may relate to abnormal cell type-specific protein interactions of the HD protein.
亨廷顿舞蹈症（HD）以基底神经节和大脑皮层中神经元的选择性易损性为显著特征。我们已经在人类和啮齿动物组织中研究了其突变会导致HD的基因（IT15）的表达情况。IT15广泛表达，在脑中表达水平最高，但在肺、睾丸、卵巢及其他组织中也有表达。在脑内，其表达呈广泛的神经元模式，且在基底神经节中并无富集。校正肌动蛋白后，HD患者脑内IT15的表达并未降低（尽管未校正时纹状体中略有下降，这与神经元丢失一致）。因此，IT15表达的广泛分布与HD神经病理变化的局限性分布并不相符。我们认为，病理生理学可能与HD蛋白异常的细胞类型特异性蛋白相互作用有关。
