Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models.
Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models.
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DOI：
10.1093/hmg/ddab052
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发表时间：
2021-05-28
影响因子：
3.5
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Kandasamy LC;Tsukamoto M;Banov V;Tsetsegee S;Nagasawa Y;Kato M;Matsumoto N;Takeda J;Itohara S;Ogawa S;Young LJ;Zhang Q
用糖基磷脂酰肌醇（GPI）对蛋白质进行翻译后修饰是所有真核生物中存在的保守机制。迄今为止，已发现超过 150 种人类 GPI 锚定蛋白，据报道约有 30 种酶参与哺乳动物 GPI 的生物合成和成熟。磷脂酰肌醇聚糖生物合成 A 类蛋白 (PIGA) 催化 GPI 锚定生物合成的第一步。携带PIGA基因突变的患者通常患有遗传性糖基磷脂酰肌醇缺乏症（IGD），并伴有顽固性癫痫和智力发育障碍。我们生成了三种具有 PIGA 缺陷的小鼠模型，分别是端脑兴奋性神经元 (Ex-M-cko)、抑制性神经元 (In-M-cko) 或丘脑神经元 (Th-H-cko)。 Ex-M-cko 和 In-M-cko 小鼠均表现出长期恐惧记忆受损，并且更容易受到红藻氨酸诱导的癫痫发作。此外，In-M-cko 表现出严重的肢体夹紧表型。在 Ex-M-cko 小鼠中观察到海马突触变化。我们的 Piga 条件敲除小鼠模型提供了强大的工具来了解遗传性 GPI 缺陷背后的细胞类型特异性机制并测试不同的治疗方式。
Posttranslational modification of a protein with glycosylphosphatidylinositol (GPI) is a conserved mechanism exists in all eukaryotes. Thus far, >150 human GPI-anchored proteins have been discovered and ~30 enzymes have been reported to be involved in the biosynthesis and maturation of mammalian GPI. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) catalyzes the very first step of GPI anchor biosynthesis. Patients carrying a mutation of the PIGA gene usually suffer from inherited glycosylphosphatidylinositol deficiency (IGD) with intractable epilepsy and intellectual developmental disorder. We generated three mouse models with PIGA deficits specifically in telencephalon excitatory neurons (Ex-M-cko), inhibitory neurons (In-M-cko) or thalamic neurons (Th-H-cko), respectively. Both Ex-M-cko and In-M-cko mice showed impaired long-term fear memory and were more susceptible to kainic acid-induced seizures. In addition, In-M-cko demonstrated a severe limb-clasping phenotype. Hippocampal synapse changes were observed in Ex-M-cko mice. Our Piga conditional knockout mouse models provide powerful tools to understand the cell-type specific mechanisms underlying inherited GPI deficiency and to test different therapeutic modalities.
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影响因子：
1.7
作者：
Kim, Young Ok;Yang, Jae Hyuk;Woo, Young Jong
通讯作者：
Woo, Young Jong
DOI：
10.1006/bbrc.2001.4334
发表时间：
2001-02-16
影响因子：
3.1
作者：
Fukamauchi, F;Aihara, O;Iwakura, Y
通讯作者：
Iwakura, Y
影响因子：
64.8
作者：
Iwasato, T;Datwani, A;Itohara, S
通讯作者：
Itohara, S
影响因子：
7.7
作者：
Lukacs, Marshall;Roberts, Tia;Stottmann, Rolf W.
通讯作者：
Stottmann, Rolf W.
DOI：
10.2183/pjab.90.130
发表时间：
2014
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Kinoshita T
通讯作者：
Kinoshita T