A knock-in reporter mouse model for Batten disease reveals predominant expression of Cln3 in visual, limbic and subcortical motor structures
A knock-in reporter mouse model for Batten disease reveals predominant expression of Cln3 in visual, limbic and subcortical motor structures
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DOI：
10.1016/j.nbd.2010.09.011
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发表时间：
2011-02-01
影响因子：
6.1
通讯作者：
Davidson, Beverly L.
中科院分区：
文献类型：
--
作者：
Ding, Song-Lin;Tecedor, Luis;Davidson, Beverly L.
幼年神经元蜡样质脂褐质沉积症（JNCL）或Batten病是由CLN3突变引起的儿童常染色体隐性遗传神经退行性疾病。JNCL的特征在于进行性视力损害、认知和运动缺陷、癫痫发作和过早死亡。关于CLN3表达神经元在神经系统中的定位的信息是有限的，特别是在发育期间。本研究使用敲入报告小鼠模型，系统地绘制了CLN3报告神经元在包括视网膜在内的整个神经系统中的空间和时间定位。CLN3报告基因主要在视觉和边缘皮质、丘脑前核和板内核、杏仁核、小脑、红核、网状结构、前庭核和视网膜中的迁移后神经元中表达。神经系统中的CLN3报告基因主要在出生后的第一个月期间表达，除了在齿状回、旁孤束核和视网膜中，在那里它在成年后仍然强烈表达。CLN3报告神经元在视觉、边缘系统和皮质下运动结构中的主要分布与JNCL的临床症状密切相关。这些发现还揭示了潜在的目标脑区域和时间段，用于未来研究疾病机制和治疗干预。(C)2010年由Elsevier Inc.出版
Juvenile neuronal ceroid lipofuscinosis (JNCL) or Batten disease is an autosomal recessive neurodegenerative disorder of children caused by mutation in CLN3. JNCL is characterized by progressive visual impairment, cognitive and motor deficits, seizures and premature death. Information about the localization of CLN3 expressing neurons in the nervous system is limited, especially during development. The present study has systematically mapped the spatial and temporal localization of CLN3 reporter neurons in the entire nervous system including retina, using a knock-in reporter mouse model. CLN3 reporter is expressed predominantly in post-migratory neurons in visual and limbic cortices, anterior and intralaminar thalamic nuclei, amygdala, cerebellum, red nucleus, reticular formation, vestibular nuclei and retina. CLN3 reporter in the nervous system is mainly expressed during the first postnatal month except in the dentate gyrus, parasolitary nucleus and retina, where it is still strongly expressed in adulthood. The predominant distribution of CLN3 reporter neurons in visual, limbic and subcortical motor structures correlates well with the clinical symptoms of JNCL. These findings have also revealed potential target brain regions and time periods for future investigations of the disease mechanisms and therapeutic intervention. (C) 2010 Published by Elsevier Inc.