Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model |
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Authors: | 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 |
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Affiliation: | Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA. |
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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. |
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