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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Animals
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Cerebellar Ataxia / genetics
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Cerebellar Ataxia / pathology
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Cerebellar Ataxia / physiopathology*
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism
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GTP-Binding Proteins / physiology*
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Genotype
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Polymerase Chain Reaction / methods
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Purkinje Cells / pathology*
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Retinal Degeneration / genetics
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Retinal Degeneration / metabolism
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Retinal Degeneration / pathology
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Retinal Degeneration / physiopathology*
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Serine-Type D-Ala-D-Ala Carboxypeptidase / genetics
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Serine-Type D-Ala-D-Ala Carboxypeptidase / metabolism
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Serine-Type D-Ala-D-Ala Carboxypeptidase / physiology*
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Zinc / metabolism*
Substances
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Serine-Type D-Ala-D-Ala Carboxypeptidase
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Agtpbp1 protein, mouse
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GTP-Binding Proteins
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Zinc