Article abstract
Nature Genetics 40, 751 - 760 (2008)
Published online: 11 May 2008 | doi:10.1038/ng.138
Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model
Kimberly L Stark1,6, Bin Xu2,6, Anindya Bagchi3, Wen-Sung Lai2, Hui Liu1, Ruby Hsu4, Xiang Wan5, Paul Pavlidis5, Alea A Mills3, Maria Karayiorgou1 & Joseph A Gogos2,4
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.
- Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
- Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
- Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
- Department of Neuroscience, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
- Department of Psychiatry and Bioinformatics Centre, University of British Columbia, 2185 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.
- These authors contributed equally to this work.
Correspondence to: Maria Karayiorgou1 e-mail: mk2758@columbia.edu
Correspondence to: Joseph A Gogos2,4 e-mail: jag90@columbia.edu
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