neurogenetics

, Volume 11, Issue 4, pp 369–378

Targeted disruption of the Mast syndrome gene SPG21 in mice impairs hind limb function and alters axon branching in cultured cortical neurons

  • Cynthia Soderblom
  • Julia Stadler
  • Henri Jupille
  • Craig Blackstone
  • Oleg Shupliakov
  • Michael C. Hanna
ORIGINAL ARTICLE

DOI: 10.1007/s10048-010-0252-7

Cite this article as:
Soderblom, C., Stadler, J., Jupille, H. et al. Neurogenetics (2010) 11: 369. doi:10.1007/s10048-010-0252-7

Abstract

Mast syndrome (SPG21) is a childhood-onset, autosomal recessive, complicated form of hereditary spastic paraplegia (HSP) characterized by dementia, thin corpus callosum, white matter abnormalities, and cerebellar and extrapyramidal signs in addition to spastic paraparesis. A nucleotide insertion resulting in premature truncation of the SPG21 gene product maspardin underlies this disorder, likely leading to loss of protein function. In this study, we generated SPG21−/− knockout mice by homologous recombination as a possible animal model for SPG21. Though SPG21−/− mice appeared normal at birth, within several months they developed gradually progressive hind limb dysfunction. Cerebral cortical neurons cultured from SPG21−/− mice exhibited significantly more axonal branching than neurons from wild-type animals, while comprehensive neuropathological analysis of SPG21−/− mice did not reveal definitive abnormalities. Since alterations in axon branching have been seen in neurons derived from animal models of other forms of HSP as well as motor neuron diseases, this may represent a common cellular pathogenic theme.

Keywords

MaspardinACP33CD4Hereditary spastic paraplegiaRab7

Abbreviations

CNS

Central nervous system

DTA

Diphtheria toxin subunit A

ES

Embryonic stem

HSP

Hereditary spastic paraplegia

MBP

Myelin basic protein

NF

Neurofilament

NGS

Normal goat serum

NMJ

Neuromuscular junction

PBS

Phosphate-buffered saline

PFA

Paraformaldehyde

TBS

Tris-buffered saline

Supplementary material

10048_2010_252_Fig8_ESM.gif (99 kb)
Supplementary Fig. S1

(GIFF 101 855 kb)

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Supplementary Fig. S1High Resolution Image (TIFF 14 936 kb)
10048_2010_252_Fig9_ESM.gif (117 kb)
Supplementary Fig. S1

(GIFF 101 855 kb)

10048_2010_252_MOESM2_ESM.tif (6.8 mb)
Supplementary Fig. S2High Resolution Image (TIFF 7 089 kb)
View video
Supplementary Video 1

SPG21+/+ mouse during the narrow beam-walking test (WMV 1,818 kb)

View video
Supplementary Video 2

SPG21−/− mouse during the narrow beam-walking test (WMV 4,115 kb)

Copyright information

© US Government 2010

Authors and Affiliations

  • Cynthia Soderblom
    • 1
    • 2
    • 3
  • Julia Stadler
    • 3
  • Henri Jupille
    • 3
  • Craig Blackstone
    • 3
  • Oleg Shupliakov
    • 2
  • Michael C. Hanna
    • 3
    • 4
  1. 1.National Institutes of Health—Karolinska Institutet Graduate Partnerships ProgramStockholmSweden
  2. 2.Department of Neuroscience, DBRM, Karolinska InstitutetStockholmSweden
  3. 3.Cellular Neurology Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of HealthBethesdaUSA
  4. 4.Department of Biological and Environmental SciencesTexas A & M University – CommerceCommerceUSA