Murine cathepsin F deficiency causes neuronal lipofuscinosis and late-onset neurological disease.
Murine cathepsin F deficiency causes neuronal lipofuscinosis and late-onset neurological disease.
复制标题
鼠组织蛋白酶 F 缺乏会导致神经元脂褐质沉着症和迟发性神经系统疾病。
DOI：
10.1128/mcb.26.6.2309-2316.2006
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发表时间：
2006
影响因子：
5.3
通讯作者：
Chapman,HaroldA
中科院分区：
文献类型：
--
作者：
Tang,Chi-Hui;Lee,Je-Wook;Galvez,MichaelG;Robillard,Liliane;Mole,SaraE;Chapman,HaroldA
组织蛋白酶F（cat F）是一种广泛表达的溶酶体半胱氨酸蛋白酶，其体内作用尚不清楚。为了解决这个问题，通过同源重组产生猫F缺陷的小鼠。虽然猫F−/−小鼠看起来健康且繁殖正常，但它们在12至16个月大时出现了进行性后腿无力和运动协调性下降，随后在6个月内体重显著减轻并死亡。发现cat F在整个中枢神经系统（CNS）中表达。猫F−/−神经元积累嗜酸性颗粒，具有溶酶体脂褐素的典型特征。大量的自体荧光脂褐素，神经退行性疾病神经元蜡样脂褐素沉积症（NCL）的特点，积累在整个中枢神经系统，但不是在内脏器官，早在6周龄开始。明显的神经胶质增生是神经元应激和神经退行性变的指标，在老年猫F−/−小鼠中也很明显。cat F是唯一的半胱氨酸组织蛋白酶，其单独失活引起小鼠中的溶酶体储存缺陷和进行性神经学特征。晚发型提示该基因可能是成人型NCL的候选基因。
Cathepsin F (cat F) is a widely expressed lysosomal cysteine protease whose in vivo role is unknown. To address this issue, mice deficient in cat F were generated via homologous recombination. Although cat F−/−mice appeared healthy and reproduced normally, they developed progressive hind leg weakness and decline in motor coordination at 12 to 16 months of age, followed by significant weight loss and death within 6 months. cat F was found to be expressed throughout the central nervous system (CNS). cat F−/−neurons accumulated eosinophilic granules that had features typical of lysosomal lipofuscin by electron microscopy. Large amounts of autofluorescent lipofuscin, characteristic of the neurodegenerative disease neuronal ceroid lipofuscinosis (NCL), accumulated throughout the CNS but not in visceral organs, beginning as early as 6 weeks of age. Pronounced gliosis, an indicator of neuronal stress and neurodegeneration, was also apparent in older cat F−/−mice. cat F is the only cysteine cathepsin whose inactivation alone causes a lysosomal storage defect and progressive neurological features in mice. The late onset suggests that this gene may be a candidate for adult-onset NCL.