Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models

被引：10

作者：

Kandasamy, Lenin C. ^{[1
]}

Tsukamoto, Mina ^{[1
]}

Banov, Vitaliy ^{[2
,3
]}

Tsetsegee, Sambuu ^{[1
]}

Nagasawa, Yutaro ^{[1
]}

Kato, Mitsuhiro ^{[4
]}

Matsumoto, Naomichi ^{[5
]}

Takeda, Junji ^{[6
]}

Itohara, Shigeyoshi ^{[2
]}

Ogawa, Sonoko ^{[7
]}

Young, Larry J. ^{[8
,9
]}

Zhang, Qi ^{[1
,2
,8
]}

机构：

[1] Univ Tsukuba, Ctr Social Neural Networks, Lab Social Neural Networks, Tsukuba, Ibaraki 3058577, Japan

[2] RIKEN, Lab Behav Genet, CBS, Wako, Saitama 3510198, Japan

[3] Univ Zurich, Inst Neuroinformat, ETH Zurich, CH-8057 Zurich, Switzerland

[4] Showa Univ, Dept Pediat, Sch Med, Tokyo 1428555, Japan

[5] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 2360004, Japan

[6] Osaka Univ, Res Inst Microbial Dis, Yabumoto Dept Intractable Dis Res, Osaka 5650871, Japan

[7] Univ Tsukuba, Fac Human Sci, Lab Behav Neuroendocrinol, Tsukuba, Ibaraki 3058577, Japan

[8] Univ Tsukuba, Fac Human Sci, Ctr Social Neural Networks, Tsukuba, Ibaraki 3058577, Japan

[9] Emory Univ, Ctr Translat Social Neurosci, Yerkes Natl Primate Res Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30329 USA

来源：

HUMAN MOLECULAR GENETICS | 2021年 / 30卷 / 09期

关键词：

SYNDROME; 2; MCAHS2; ANCHORED PROTEINS; GERMLINE MUTATION; PIGA MUTATION; FAMILY; DISRUPTION; EPILEPSY; GROWTH; SPERM;

D O I：

10.1093/hmg/ddab052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 similar to 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.

引用

页码：758 / 770

页数：13

共 48 条

[1] The vesicular GABA transporter vGAT, is present in sperm and testis [J].