Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon 122 050, India.
Neurobiol Dis. 2010 Dec;40(3):586-92. doi: 10.1016/j.nbd.2010.08.002. Epub 2010 Aug 6.
E6 associated protein is an E3 ubiquitin ligase encoded by the gene Ube3a. Deletion or loss of function of the maternally inherited allele of Ube3a leads to Angelman syndrome. In the present study, we show that maternal loss of Ube3a (Ube3a(m-/p+)) in the mouse model leads to motor deficits that could be attributed to the dysfunction of the nigrostriatal pathway. The number of tyrosine hydroxylase positive neurons in the substantia nigra was significantly reduced in Ube3a(m-/p+) mice as compared to the wild type counterparts. The Ube3a(m-/p+) mice performed poorly in behavioural paradigms sensitive to nigrostriatal dysfunction. Even though the tyrosine hydroxylase staining was apparently the same in the striatum of both genotypes, the presynaptic and postsynaptic proteins were significantly reduced in Ube3a(m-/p+) mice. These findings suggest that the abnormality in the nigrostriatal pathway along with the cerebellum produces the observed motor dysfunctions in Ube3a(m-/p+) mice.
E6 相关蛋白是由 Ube3a 基因编码的 E3 泛素连接酶。Ube3a 母系遗传等位基因的缺失或功能丧失会导致 Angelman 综合征。在本研究中，我们表明，在小鼠模型中，Ube3a（Ube3a(m-/p+)) 的母系缺失会导致运动功能障碍，这可能归因于黑质纹状体通路的功能障碍。与野生型相比，Ube3a(m-/p+) 小鼠中黑质纹状体通路中的酪氨酸羟化酶阳性神经元数量明显减少。Ube3a(m-/p+) 小鼠在对黑质纹状体功能障碍敏感的行为范式中表现不佳。尽管两种基因型纹状体中的酪氨酸羟化酶染色明显相同，但 Ube3a(m-/p+) 小鼠中的突触前和突触后蛋白明显减少。这些发现表明，黑质纹状体通路以及小脑的异常导致了 Ube3a(m-/p+) 小鼠观察到的运动功能障碍。
