Nna1的锌结合结构域是预防浦肯野细胞变性（pcd）小鼠视网膜光感受器丧失和小脑共济失调所必需的。
The zinc-binding domain of Nna1 is required to prevent retinal photoreceptor loss and cerebellar ataxia in Purkinje cell degeneration (pcd) mice.
作者信息
Chakrabarti Lisa, Eng Jeremiah, Martinez Refugio A, Jackson Stephen, Huang Jing, Possin Daniel E, Sopher Bryce L, La Spada Albert R
机构信息
Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USA.
出版信息
Vision Res. 2008 Sep;48(19):1999-2005. doi: 10.1016/j.visres.2008.05.026. Epub 2008 Jul 26.
Abstract
The Purkinje cell degeneration (pcd) mouse undergoes retinal photoreceptor degeneration and Purkinje cell loss. Nna1 is postulated to be the causal gene for pcd. We show that a BAC containing the Nna1 gene rescues retinal photoreceptor loss and Purkinje cell degeneration, confirming that Nna1 loss-of-function is responsible for these phenotypes. Mutation of the zinc-binding domain within the transgene destroyed its ability to rescue neuronal loss in pcd(5J) homozygous mice. In conclusion, Nna1 is required for survival of retinal photoreceptors and other neuron populations that degenerate in pcd mice. A functional zinc-binding domain is crucial for Nna1 to support neuron survival.
摘要
浦肯野细胞变性（pcd）小鼠会发生视网膜光感受器变性和浦肯野细胞丢失。据推测，Nna1是pcd的致病基因。我们发现，一个包含Nna1基因的细菌人工染色体（BAC）可挽救视网膜光感受器丢失和浦肯野细胞变性，这证实了Nna1功能丧失是导致这些表型的原因。转基因内锌结合结构域的突变破坏了其挽救pcd(5J)纯合小鼠神经元丢失的能力。总之，Nna1是视网膜光感受器和pcd小鼠中发生变性的其他神经元群体存活所必需的。一个功能性锌结合结构域对Nna1支持神经元存活至关重要。
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