title: Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model.
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.
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Stark
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Anindya
authors.initials: A
authors.lastname: Bagchi
authors.forename: Wen-Sung
authors.initials: WS
authors.lastname: Lai
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Ruby
authors.initials: R
authors.lastname: Hsu
authors.forename: Xiang
authors.initials: X
authors.lastname: Wan
authors.forename: Paul
authors.initials: P
authors.lastname: Pavlidis
authors.forename: Alea A
authors.initials: AA
authors.lastname: Mills
authors.forename: Maria
authors.initials: M
authors.lastname: Karayiorgou
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gogos
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006185:Habituation, Psychophysiologic / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011506:Proteins / Q000502:physiology; D016601:RNA-Binding Proteins; D012678:Sensation Disorders / Q000235:genetics; D013131:Spine / Q000033:anatomy & histology / Q000254:growth & development
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins