Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity in the ∆7 SMA Mouse

McGovern, V.L., Massoni-Laporte, A., Wang, X., Le, T.T., Le, H.T., Beattie, C.E., Rich, M.M., Burghes, A.H.
PLoS One   10: e0132364 (Journal)
Registered Authors
Beattie, Christine
Spinal cord, Mouse models, Genetically modified animals, Motor neurons, Phenotypes, Hyperexpression techniques, Neuromuscular junctions, Muscle electrophysiology
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/chemistry
  • Female
  • Genes, Reporter
  • Humans
  • Male
  • Membrane Glycoproteins/biosynthesis
  • Membrane Glycoproteins/genetics
  • Membrane Glycoproteins/physiology*
  • Mice
  • Mice, Knockout
  • Microfilament Proteins/biosynthesis
  • Microfilament Proteins/genetics
  • Microfilament Proteins/physiology*
  • Morpholinos/administration & dosage
  • Morpholinos/genetics
  • Motor Neurons/metabolism*
  • Muscular Atrophy, Spinal/genetics
  • Muscular Atrophy, Spinal/therapy*
  • Neuromuscular Junction/physiopathology
  • Phenotype
  • Prions/genetics
  • Promoter Regions, Genetic
  • RNA, Messenger/administration & dosage
  • RNA, Messenger/biosynthesis
  • RNA, Messenger/genetics
  • Recombinant Proteins/biosynthesis
  • Sex Characteristics
  • Spinal Cord/metabolism*
  • Survival of Motor Neuron 1 Protein/genetics
  • Transgenes
  • Zebrafish/embryology
26134627 Full text @ PLoS One
Spinal muscular atrophy is caused by loss of the SMN1 gene and retention of SMN2. The SMN2 copy number inversely correlates with phenotypic severity and is a modifier of disease outcome. The SMN2 gene essentially differs from SMN1 by a single nucleotide in exon 7 that modulates the incorporation of exon 7 into the final SMN transcript. The majority of the SMN2 transcripts lack exon 7 and this leads to a SMN protein that does not effectively oligomerize and is rapidly degraded. However the SMN2 gene does produce some full-length SMN and the SMN2 copy number along with how much full-length SMN the SMN2 gene makes correlates with severity of the SMA phenotype. However there are a number of discordant SMA siblings that have identical haplotypes and SMN2 copy number yet one has a milder form of SMA. It has been suggested that Plastin3 (PLS3) acts as a sex specific phenotypic modifier where increased expression of PLS3 modifies the SMA phenotype in females. To test the effect of PLS3 overexpression we have over expressed full-length PLS3 in SMA mice. To ensure no disruption of functionality or post-translational processing of PLS3 we did not place a tag on the protein. PLS3 protein was expressed under the Prion promoter as we have shown previously that SMN expression under this promoter can rescue SMA mice. High levels of PLS3 mRNA were expressed in motor neurons along with an increased level of PLS3 protein in total spinal cord, yet there was no significant beneficial effect on the phenotype of SMA mice. Specifically, neither survival nor the fundamental electrophysiological aspects of the neuromuscular junction were improved upon overexpression of PLS3 in neurons.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes