Deficiency of the zinc finger protein ZPR1 causes neurodegeneration.
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.
Doran
Beth
B
Program in Molecular Medicine, Department of Cell Biology, and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Gherbesi
Norberto
N
Hendricks
Gregory
G
Flavell
Richard A
RA
Davis
Roger J
RJ
Gangwani
Laxman
L
D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018450:Disease Progression; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016335:Zinc Fingers
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490987:Zfp259 protein, mouse