气候变化领域集成服务门户(CCPortal): Defective myelination in an RNA polymerase III mutant leukodystrophic mouse

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DOI	10.1073/pnas.2024378118
	Defective myelination in an RNA polymerase III mutant leukodystrophic mouse
	Merheb E.; Cui M.-H.; DuBois J.C.; Branch C.A.; Gulinello M.; Shafit-Zagardo B.; Moir R.D.; Willis I.M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:40
英文摘要	RNA polymerase (Pol) III synthesizes abundant short noncoding RNAs that have essential functions in protein synthesis, secretion, and other processes. Despite the ubiquitous functions of these RNAs, mutations in Pol III subunits cause Pol III-related leukodystrophy, an early-onset neurodegenerative disease. The basis of this neural sensitivity and the mechanisms of disease pathogenesis are unknown. Here we show that mice expressing pathogenic mutations in the largest Pol III subunit, Polr3a, specifically in Olig2-expressing cells, have impaired growth and developmental delay, deficits in cognitive, sensory, and fine sensorimotor function, and hypomyelination in multiple regions of the cerebrum and spinal cord. These phenotypes reflect a subset of clinical features seen in patients. In contrast, the gross motor defects and cerebellar hypomyelination that are common features of severely affected patients are absent in the mice, suggesting a relatively mild form of the disease in this conditional model. Our results show that disease pathogenesis in the mice involves defects that reduce both the number of mature myelinating oligodendrocytes and the ability of these cells to produce a myelin sheath of normal thickness. The findings suggest unique sensitivities of oligodendrogenesis and myelination to perturbations of Pol III transcription. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Hypomyelination; Leukodystrophy; Oligodendrocyte; RNA polymerase III
语种	英语
scopus关键词	cell protein; CNP protein; DNA directed RNA polymerase III; MBP protein; myelin oligodendrocyte glycoprotein; QKI protein; unclassified drug; adolescent; adult; animal cell; animal experiment; animal model; animal tissue; Article; body weight; cell count; cell function; cell population; clinical feature; cognitive defect; controlled study; demyelinating disease; developmental delay; female; gene; gene mutation; genetic transcription; growth disorder; hypomyelination; leukodystrophy; male; mouse; myelination; neuropathy; newborn; nonhuman; oligodendrogenesis; oligodendroglia; pathogenesis; phenotype; Polr3a gene; sensorimotor deficit; sensory dysfunction; sex difference
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238788
作者单位	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States; Department of Radiology, Albert Einstein College of Medicine, Bronx, NY 10461, United States; Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, United States; Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, United States; Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, United States; Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY 10461, United States
推荐引用方式 GB/T 7714	Merheb E.,Cui M.-H.,DuBois J.C.,et al. Defective myelination in an RNA polymerase III mutant leukodystrophic mouse[J],2021,118(40).
APA	Merheb E..,Cui M.-H..,DuBois J.C..,Branch C.A..,Gulinello M..,...&Willis I.M..(2021).Defective myelination in an RNA polymerase III mutant leukodystrophic mouse.Proceedings of the National Academy of Sciences of the United States of America,118(40).
MLA	Merheb E.,et al."Defective myelination in an RNA polymerase III mutant leukodystrophic mouse".Proceedings of the National Academy of Sciences of the United States of America 118.40(2021).