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

Kimberly L. Stark, Bin Xu, Anindya Bagchi, Wen Sung Lai, Hui Liu, Ruby Hsu, Xiang Wan, Paul Pavlidis, Alea A. Mills, Maria Karayiorgou, Joseph A. Gogos

Research output: Contribution to journalArticlepeer-review

421 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)751-760
Number of pages10
JournalNature Genetics
Volume40
Issue number6
DOIs
StatePublished - Jun 1 2008

Fingerprint Dive into the research topics of 'Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model'. Together they form a unique fingerprint.

Cite this