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

作者：Stark Kimberly L; Xu Bin; Bagchi Anindya; Lai Wen Sung; Liu Hui; Hsu Ruby; Wan Xiang; Pavlidis Paul; Mills Alea A; Karayiorgou Maria; Gogos Joseph A^*

来源：Nature Genetics, 2008, 40(6): 751-760.

DOI：10.1038/ng.138

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.

• 出版日期2008-6