Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model.
Nat Genet, 2008/6;40(6):751-60.
Stark KL[1], Xu B, Bagchi A, Lai WS, Liu H, Hsu R, Wan X, Pavlidis P, Mills AA, Karayiorgou M, Gogos JA
Affiliations
PMID: 18469815DOI: 10.1038/ng.138
Impact factor: 41.307
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.
MeSH terms
Animals; Behavior, Animal; Brain; Chromosome Deletion; Chromosomes, Human, Pair 22; Cognition Disorders; Disease Models, Animal; Female; Gene Expression Profiling; Habituation, Psychophysiologic; Heterozygote; Humans; Learning Disabilities; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Oligonucleotide Array Sequence Analysis; Phenotype; Proteins; RNA-Binding Proteins; Sensation Disorders; Spine
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