Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, United States; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States.
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, United States; Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR, United States.
Neurobiol Dis. 2018 Nov;119:65-78. doi: 10.1016/j.nbd.2018.07.013. Epub 2018 Jul 23.
We have identified a natural Japanese macaque model of the childhood neurodegenerative disorder neuronal ceroid lipofuscinosis, commonly known as Batten Disease, caused by a homozygous frameshift mutation in the CLN7 gene (CLN7). Affected macaques display progressive neurological deficits including visual impairment, tremor, incoordination, ataxia and impaired balance. Imaging, functional and pathological studies revealed that CLN7 macaques have reduced retinal thickness and retinal function early in disease, followed by profound cerebral and cerebellar atrophy that progresses over a five to six-year disease course. Histological analyses showed an accumulation of cerebral, cerebellar and cardiac storage material as well as degeneration of neurons, white matter fragmentation and reactive gliosis throughout the brain of affected animals. This novel CLN7 macaque model recapitulates key behavioral and neuropathological features of human Batten Disease and provides novel insights into the pathophysiology linked to CLN7 mutations. These animals will be invaluable for evaluating promising therapeutic strategies for this devastating disease.
我们已经鉴定出一种日本猕猴幼年神经退行性疾病神经元蜡样脂褐质沉积症（神经元蜡样脂褐质沉积病）的天然模型，这种疾病通常被称为巴滕病，是由 CLN7 基因（CLN7）的纯合移码突变引起的。受影响的猕猴表现出进行性神经功能缺损，包括视力障碍、震颤、协调障碍、共济失调和平衡受损。影像学、功能和病理学研究表明，CLN7 猕猴在疾病早期就出现视网膜厚度和视网膜功能降低，随后出现严重的大脑和小脑萎缩，疾病过程持续五到六年。组织学分析显示，受影响动物的大脑、小脑和心脏储存物质积累，以及神经元变性、白质碎裂和反应性神经胶质增生。这种新型 CLN7 猕猴模型再现了人类巴滕病的关键行为和神经病理学特征，并为与 CLN7 突变相关的病理生理学提供了新的见解。这些动物将对评估这种毁灭性疾病的有希望的治疗策略具有重要价值。
