Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model.
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.
Stark
Kimberly L
KL
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
Xu
Bin
B
Bagchi
Anindya
A
Lai
Wen-Sung
WS
Liu
Hui
H
Hsu
Ruby
R
Wan
Xiang
X
Pavlidis
Paul
P
Mills
Alea A
AA
Karayiorgou
Maria
M
Gogos
Joseph A
JA
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
C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins