An inducible mouse model of late onset Tay-Sachs disease
An inducible mouse model of late onset Tay-Sachs disease
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DOI：
10.1006/nbdi.2002.0511
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发表时间：
2002-08-01
影响因子：
6.1
通讯作者：
Platt, FM
中科院分区：
文献类型：
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作者：
Jeyakumar, M;Smith, D;Platt, FM
GM2神经节苷脂沉积症（包括泰-萨克斯病和桑德霍夫病）的小鼠模型分别在己糖胺酶α和β亚基上缺失。桑德霍夫（Hexb - / -）小鼠患有严重的神经系统疾病，模拟人类婴儿型发病变体。然而，泰-萨克斯（Hexa - / -）小鼠模型缺乏明显的表型，因为小鼠可以部分绕过受阻的分解代谢途径从而避免患病。我们研究了一部分泰-萨克斯小鼠是否会发生迟发性疾病。我们发现，大约65%的小鼠在其自然寿命内出现一种或多种该疾病的临床症状（n = 52，P < 0.0001）。然而，100%有多次繁殖史的雌性小鼠在更年轻时就患上迟发性疾病（n = 21，P < 0.0001），并表现出所有临床特征。对一大批雌性泰-萨克斯小鼠进行多次繁殖证实，怀孕会诱发泰-萨克斯病迟发性发作。症状的发作与己糖胺酶B（旁路途径的一个组成部分）上调减少相关。（C）2002年爱思唯尔科学（美国）
Mouse models of the G(M2) gangliosidoses, Tay-Sachs and Sandhoff disease, are null for the hexosaminidase alpha and beta subunits respectively. The Sandhoff (Hexb-l-) mouse has severe neurological disease and mimics the human infantile onset variant. However, the Tay-Sachs (Hexa-l-) mouse model lacks an overt phenotype as mice can partially bypass the blocked catabolic pathway and escape disease. We have investigated whether a subset of Tay-Sachs mice develop late onset disease. We have found that similar to65% of the mice develop one or more clinical signs of the disease within their natural life span (n = 52, P < 0.0001). However, 100% of female mice with repeat breeding histories developed late onset disease at an earlier age (n = 21, P < 0.0001) and displayed all clinical features. Repeat breeding of a large cohort of female Tay-Sachs mice confirmed that pregnancy induces late onset Tay-Sachs disease. Onset of symptoms correlated with reduced up-regulation of hexosaminidase B, a component of the bypass pathway. (C) 2002 Elsevier Science (USA).