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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Behavior, Animal / physiology*
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Brain / physiology*
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Chromosome Deletion*
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Chromosomes, Human, Pair 22 / genetics*
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Cognition Disorders / genetics
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Disease Models, Animal*
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Female
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Gene Expression Profiling
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Habituation, Psychophysiologic / genetics
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Heterozygote
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Humans
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Learning Disabilities / genetics
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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MicroRNAs / biosynthesis*
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MicroRNAs / genetics*
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Oligonucleotide Array Sequence Analysis
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Phenotype
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Proteins / physiology
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RNA-Binding Proteins
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Sensation Disorders / genetics
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Spine / anatomy & histology
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Spine / growth & development
Substances
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Dgcr8 protein, mouse
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MicroRNAs
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Proteins
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RNA-Binding Proteins