| First Author | Greten-Harrison B | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 45 | Pages | 19573-8 |
| PubMed ID | 20974939 | Mgi Jnum | J:167549 |
| Mgi Id | MGI:4868532 | Doi | 10.1073/pnas.1005005107 |
| Citation | Greten-Harrison B, et al. (2010) alphabetagamma-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Proc Natl Acad Sci U S A 107(45):19573-8 |
| abstractText | Synucleins are a vertebrate-specific family of abundant neuronal proteins. They comprise three closely related members, alpha-, beta-, and gamma-synuclein. alpha-Synuclein has been the focus of intense attention since mutations in it were identified as a cause for familial Parkinson's disease. Despite their disease relevance, the normal physiological function of synucleins has remained elusive. To address this, we generated and characterized alphabetagamma-synuclein knockout mice, which lack all members of this protein family. Deletion of synucleins causes alterations in synaptic structure and transmission, age-dependent neuronal dysfunction, as well as diminished survival. Abrogation of synuclein expression decreased excitatory synapse size by approximately 30% both in vivo and in vitro, revealing that synucleins are important determinants of presynaptic terminal size. Young synuclein null mice show improved basic transmission, whereas older mice show a pronounced decrement. The late onset phenotypes in synuclein null mice were not due to a loss of synapses or neurons but rather reflect specific changes in synaptic protein composition and axonal structure. Our results demonstrate that synucleins contribute importantly to the long-term operation of the nervous system and that alterations in their physiological function could contribute to the development of Parkinson's disease. |
