Deficiency of the zinc finger protein ZPR1 causes neurodegeneration

Proc Natl Acad Sci U S A. 2006 May 9;103(19):7471-5. doi: 10.1073/pnas.0602057103. Epub 2006 Apr 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Axons / metabolism
  • Axons / pathology
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Disease Progression
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Microtubules / genetics
  • Microtubules / metabolism
  • Microtubules / pathology
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Motor Neurons / ultrastructure
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology*
  • Zinc Fingers


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Zfp259 protein, mouse