Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model

被引：452

作者：

Stark, Kimberly L. ^{[2
]}

Xu, Bin ^{[1
]}

Bagchi, Anindya ^{[3
]}

Lai, Wen-Sung ^{[1
]}

Liu, Hui ^{[2
]}

Hsu, Ruby ^{[4
]}

Wan, Xiang ^{[5
,6
]}

Pavlidis, Paul ^{[5
,6
]}

Mills, Alea A. ^{[3
]}

Karayiorgou, Maria ^{[2
]}

Gogos, Joseph A. ^{[1
,4
]}

机构：

[1] Columbia Univ, Dept Physiol & Cellular Biophys, Coll Phys & Surg, New York, NY 10032 USA

[2] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA

[3] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[4] Columbia Univ, Dept Neurosci, Coll Phys & Surg, New York, NY 10032 USA

[5] Univ British Columbia, Dept Psychiat, Vancouver, BC V6T 1Z4, Canada

[6] Univ British Columbia, Bioinformat Ctr, Vancouver, BC V6T 1Z4, Canada

来源：

NATURE GENETICS | 2008年 / 40卷 / 06期

关键词：

D O I：

10.1038/ng.138

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Individuals with 22q11.2 microdeletions show behavioral and cognitive deficits and are at high risk of developing schizophrenia. We analyzed an engineered mouse strain carrying a chromosomal deficiency spanning a segment syntenic to the human 22q11.2 locus. We uncovered a previously unknown alteration in the biogenesis of microRNAs (miRNAs) and identified a subset of brain miRNAs affected by the microdeletion. We provide evidence that the abnormal miRNA biogenesis emerges because of haploinsufficiency of the Dgcr8 gene, which encodes an RNA-binding moiety of the 'microprocessor' complex and contributes to the behavioral and neuronal deficits associated with the 22q11.2 microdeletion.

引用

页码：751 / 760

页数：10

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