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

Stark, K. L., Xu, B., Bagchi, A., Lai, W. S., Liu, H., Hsu, R., Wan, X., Pavlidis, P., Mills, A. A., Karayiorgou, M., Gogos, J. A. (June 2008) Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet, 40 (6). pp. 751-760.

URL: http://www.ncbi.nlm.nih.gov/pubmed/18469815

DOI: 10.1038/ng.138

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.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal organs, tissues, organelles, cell types and functions > organs types and functions > brain bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA organism description > model organism organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions > organs types and functions organs, tissues, organelles, cell types and functions
CSHL Authors:	Mills, Alea A.
Communities:	CSHL labs > Mills lab
Depositing User:	Matt Covey
Date:	June 2008
Date Deposited:	28 Feb 2013 16:50
Last Modified:	28 Feb 2013 16:50
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27488

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