Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model
Journal
Nature Genetics
Journal Volume
40
Journal Issue
6
Pages
751-760
Date Issued
2008
Author(s)
Kimberly L Stark et al.
Xu, B.
Bagchi, A.
Hsu, R.
Wan, X.
Pavlidis, P.
Mills, A.A.
Karayiorgou, M.
Gogos, J.A.
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.
SDGs
Type
journal article