| RRC ID |
88453
|
| 著者 |
Kandasamy LC, Tsukamoto M, Banov V, Tsetsegee S, Nagasawa Y, Kato M, Matsumoto N, Takeda J, Itohara S, Ogawa S, Young LJ, Zhang Q.
|
| タイトル |
Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models.
|
| ジャーナル |
Hum Mol Genet
|
| Abstract |
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.
|
| 巻・号 |
30(9)
|
| ページ |
758-770
|
| 公開日 |
2021-5-28
|
| DOI |
10.1093/hmg/ddab052
|
| PII |
6145030
|
| PMID |
33607654
|
| PMC |
PMC8161520
|
| MeSH |
Animals
Cognition
Glycosylphosphatidylinositols* / deficiency
Humans
Kainic Acid* / metabolism
Mammals
Mice
Mice, Knockout
Mutation
Neurons / metabolism
Seizures / genetics
Seizures / metabolism
|
| リソース情報 |
| 実験動物マウス |
RBRC06211 |
