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Nat Genet. 2008 Jun;40(6):751-60. doi: 10.1038/ng.138. Epub 2008 May 11.

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

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1
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.

Abstract

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.

PMID:
18469815
DOI:
10.1038/ng.138
[Indexed for MEDLINE]
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