Reference - Detail
| RRC ID | 64542 |
|---|---|
| Author | Fujitani M, Zhang S, Fujiki R, Fujihara Y, Yamashita T. |
| Title | A chromosome 16p13.11 microduplication causes hyperactivity through dysregulation of miR-484/protocadherin-19 signaling. |
| Journal | Mol Psychiatry |
| Abstract |
Chromosome 16p13.11 microduplication is a risk factor associated with various neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, intellectual disabilities, developmental delay and autistic spectrum disorder. The underlying molecular mechanism of this genetic variation remained unknown, but its core genetic locus-conserved across mice and humans-contains seven genes. Here, we generated bacterial artificial chromosome-transgenic mice carrying a human 16p13.11 locus, and these mice showed the behavioral hyperactivity phenotype. We identified miR-484 as the responsible gene using a combination of expression and functional analyses. Mature miR-484 was expressed during active cortical neurogenesis, and overexpression of miR-484 decreased proliferation and increased neural progenitor differentiation in vivo. Luciferase screening identified the 3'-untranslated region of protocadherin-19 (Pcdh19) as a target of miR-484. The effect of miR-484 on neurogenesis was rescued by ectopic PCDH19 expression. These results demonstrate that miR-484 promotes neurogenesis by inhibiting PCDH19. Dysregulation of neurogenesis by imbalanced miR-484/PCDH19 expression contributes to the pathogenesis of 16p13.11 microduplication syndrome. |
| Volume | 22(3) |
| Pages | 364-374 |
| Published | 2017-3-1 |
| DOI | 10.1038/mp.2016.106 |
| PII | mp2016106 |
| PMID | 27378146 |
| PMC | PMC5322274 |
| MeSH | Animals Attention Deficit Disorder with Hyperactivity / genetics* Cadherins / genetics Cadherins / metabolism Cell Differentiation Chromosomes, Human, Pair 16 / genetics Developmental Disabilities / genetics Gene Duplication / genetics Genetic Predisposition to Disease / genetics Humans Hyperkinesis Mice Mice, Transgenic MicroRNAs / genetics* MicroRNAs / metabolism* Neurogenesis / genetics Protocadherins Risk Factors Signal Transduction / genetics |
| IF | 12.384 |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 32 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |