The zinc-binding domain of Nna1 is required to prevent retinal photoreceptor loss and cerebellar ataxia in Purkinje cell degeneration (pcd) mice

被引：30

作者：

Chakrabarti, Lisa ^{[1
]}

Eng, Jeremiah ^{[1
]}

Martinez, Refugio A. ^{[1
]}

Jackson, Stephen ^{[1
]}

Huang, Jing ^{[2
]}

Possin, Daniel E. ^{[2
]}

Sopher, Bryce L. ^{[1
]}

La Spada, Albert R. ^{[1
,3
,4
,5
,6
]}

机构：

[1] Univ Washington, Med Ctr, Dept Lab Med, Seattle, WA 98195 USA

[2] Univ Washington, Med Ctr, Dept Ophthalmol, Seattle, WA 98195 USA

[3] Univ Washington, Med Ctr, Dept Neurol Neurogenet, Seattle, WA 98195 USA

[4] Univ Washington, Med Ctr, Dept Ctr Neurogenet & Neurotherapeut, Seattle, WA 98195 USA

[5] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA

[6] Univ Washington, Med Ctr, Dept Med Med Genet, Seattle, WA 98195 USA

来源：

VISION RESEARCH | 2008年 / 48卷 / 19期

关键词：

retinal photoreceptor degeneration; zinc-dependent carboxypeptidase; genetic rescue; Purkinje cell degeneration;

D O I：

10.1016/j.visres.2008.05.026

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1999 / 2005

页数：7

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