論文 - 詳細
| RRC ID | 33075 |
|---|---|
| 著者 | Mullin AP, Sadanandappa MK, Ma W, Dickman DK, VijayRaghavan K, Ramaswami M, Sanyal S, Faundez V. |
| タイトル | Gene dosage in the dysbindin schizophrenia susceptibility network differentially affect synaptic function and plasticity. |
| ジャーナル | J Neurosci |
| Abstract |
Neurodevelopmental disorders arise from single or multiple gene defects. However, the way multiple loci interact to modify phenotypic outcomes remains poorly understood. Here, we studied phenotypes associated with mutations in the schizophrenia susceptibility gene dysbindin (dysb), in isolation or in combination with null alleles in the dysb network component Blos1. In humans, the Blos1 ortholog Bloc1s1 encodes a polypeptide that assembles, with dysbindin, into the octameric BLOC-1 complex. We biochemically confirmed BLOC-1 presence in Drosophila neurons, and measured synaptic output and complex adaptive behavior in response to BLOC-1 perturbation. Homozygous loss-of-function alleles of dysb, Blos1, or compound heterozygotes of these alleles impaired neurotransmitter release, synapse morphology, and homeostatic plasticity at the larval neuromuscular junction, and impaired olfactory habituation. This multiparameter assessment indicated that phenotypes were differentially sensitive to genetic dosages of loss-of-function BLOC-1 alleles. Our findings suggest that modification of a second genetic locus in a defined neurodevelopmental regulatory network does not follow a strict additive genetic inheritance, but rather, precise stoichiometry within the network determines phenotypic outcomes. |
| 巻・号 | 35(1) |
| ページ | 325-38 |
| 公開日 | 2015-1-7 |
| DOI | 10.1523/JNEUROSCI.3542-14.2015 |
| PII | 35/1/325 |
| PMID | 25568125 |
| PMC | PMC4287151 |
| MeSH | Animals Animals, Genetically Modified Carrier Proteins / genetics* Drosophila Drosophila Proteins / genetics* Dysbindin Dystrophin-Associated Proteins Female Gene Dosage / physiology* Nerve Net / physiology* Nerve Net / ultrastructure Neuronal Plasticity / physiology* Schizophrenia / genetics* Schizophrenia / physiopathology Synapses / genetics* Synapses / ultrastructure Synaptic Transmission / physiology |
| IF | 5.674 |
| 引用数 | 25 |
| WOS 分野 | NEUROSCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | 6856R-1 6856R-2 |