Deficiency of the zinc finger protein ZPR1 causes neurodegeneration
Program in Molecular Medicine and Howard Hughes Medical Institute; Department of Cell Biology
Animals; Apoptosis; Axons; Carrier Proteins; Cell Differentiation; Cells, Cultured; Disease Progression; Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Microtubules; Motor Neurons; Nerve Degeneration; Zinc Fingers
Life Sciences | Medicine and Health Sciences
Mutations that cause reduced expression of the full-length Survival Motor Neurons (SMN) protein are a major cause of spinal muscular atrophy (SMA), a disease characterized by degeneration of the alpha-motor neurons in the anterior horn of the spinal cord. The severity of SMA may be influenced by the actions of modifier genes. One potential modifier gene is represented by ZPR1, which is down-regulated in patients with SMA and encodes a zinc finger protein that interacts with complexes formed by SMN. To test the functional significance of ZPR1 gene down-regulation, we examined a mouse model with targeted ablation of the Zpr1 gene. We report that ZPR1-deficient mice exhibit axonal pathology and neurodegeneration. These data identify ZPR1 deficiency as a contributing factor in neurodegenerative disorders.
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Citation: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7471-5. Epub 2006 Apr 28. Link to article on publisher's site