PUBLICATION

Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy

Authors
Sleigh, J.N., Barreiro-Iglesias, A., Oliver, P.L., Biba, A., Becker, T., Davies, K.E., Becker, C.G., and Talbot, K.
ID
ZDB-PUB-131024-16
Date
2014
Source
Human molecular genetics   23(4): 855-69 (Journal)
Registered Authors
Barreiro-Iglesias, Antón, Becker, Catherina G., Becker, Thomas, Davies, Kay
Keywords
none
MeSH Terms
  • Animals
  • Cell Line
  • Cell Survival
  • Humans
  • Lectins, C-Type/metabolism*
  • Mice
  • Mice, Transgenic
  • Motor Neurons/metabolism*
  • Muscular Atrophy, Spinal/metabolism*
  • Muscular Atrophy, Spinal/pathology
  • Neurites/metabolism
  • Spinal Cord/metabolism
  • Spinal Cord/pathology
  • Survival of Motor Neuron 1 Protein/genetics
  • Survival of Motor Neuron 1 Protein/metabolism
  • Zebrafish
PubMed
24067532 Full text @ Hum. Mol. Genet.
Abstract

Spinal muscular atrophy (SMA) is characterized by the selective loss of spinal motor neurons owing to reduced levels of survival motor neuron (Smn) protein. In addition to its well-established role in assembling constituents of the spliceosome, diverse cellular functions have been proposed for Smn, but the reason why low levels of this widely expressed protein result in selective motor neuron pathology is still debated. In longitudinal studies of exon-level changes in SMA mouse model tissues, designed to determine the contribution of splicing dysfunction to the disease, we have previously shown that a generalized defect in splicing is unlikely to play a causative role in SMA. Nevertheless, we identified a small subset of genes that were alternatively spliced in the spinal cord compared with control mice before symptom onset, indicating a possible mechanistic role in disease. Here, we have performed functional studies of one of these genes, chondrolectin (Chodl), known to be highly expressed in motor neurons and important for correct motor axon outgrowth in zebrafish. Using in vitro and in vivo models of SMA, we demonstrate altered expression of Chodl in SMA mouse spinal motor neurons, show that Chodl has distinct effects on cell survival and neurite outgrowth and that increasing the expression of chodl can rescue motor neuron outgrowth defects in Smn-depleted zebrafish. Our findings thus link the dysregulation of Chodl to the pathophysiology of motor neuron degeneration in SMA.

Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes