Overexpression of human wildtype torsinA and human ¿GAG torsinA in a transgenic mouse model causes phenotypic abnormalities

K. Grundmann, B. Reischmann, G. Vanhoutte, J. Hübener, P. Teismann, T.-K. Hauser, M. Bonin, J. Wilbertz, S. Horn, H. P. Nguyen, M. Kuhn, S. Chanarat, H. Wolburg, A. Van der Linden, O. Riess

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Primary torsion dystonia is an autosomal-dominant inherited movement disorder. Most cases are caused by an in-frame deletion (GAG) of the DYT1 gene encoding torsinA. Reduced penetrance and phenotypic variability suggest that alteration of torsinA amino acid sequence is necessary but not sufficient for development of clinical symptoms and that additional factors must contribute to the factual manifestation of the disease. We generated 4 independent transgenic mouse lines, two overexpressing human mutant torsinA and two overexpressing human wildtype torsinA using a strong murine prion protein promoter. Our data provide for the first time in vivo evidence that not only mutant torsinA is detrimental to neuronal cells but that also wildtype torsinA can lead to neuronal dysfunction when overexpressed at high levels. This hypothesis is supported by (i) neuropathological findings, (ii) neurochemistry, (iii) behavioral abnormalities and (iv) DTI-MRI analysis.

Original languageEnglish
Pages (from-to)190-206
Number of pages17
JournalNeurobiology of Disease
Volume27
Issue number2
Early online date18 May 2007
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Animals
  • Blotting, Western
  • Brain
  • Brain Chemistry
  • Dystonia
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Transmission
  • Molecular Chaperones
  • Motor Activity
  • Neurons
  • Neurotransmitter Agents
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction

Cite this

Grundmann, K., Reischmann, B., Vanhoutte, G., Hübener, J., Teismann, P., Hauser, T-K., ... Riess, O. (2007). Overexpression of human wildtype torsinA and human ¿GAG torsinA in a transgenic mouse model causes phenotypic abnormalities. Neurobiology of Disease, 27(2), 190-206. https://doi.org/10.1016/j.nbd.2007.04.015

Overexpression of human wildtype torsinA and human ¿GAG torsinA in a transgenic mouse model causes phenotypic abnormalities. / Grundmann, K.; Reischmann, B.; Vanhoutte, G.; Hübener, J.; Teismann, P.; Hauser, T.-K.; Bonin, M.; Wilbertz, J.; Horn, S.; Nguyen, H. P.; Kuhn, M.; Chanarat, S.; Wolburg, H.; Van der Linden, A.; Riess, O.

In: Neurobiology of Disease, Vol. 27, No. 2, 08.2007, p. 190-206.

Research output: Contribution to journalArticle

Grundmann, K, Reischmann, B, Vanhoutte, G, Hübener, J, Teismann, P, Hauser, T-K, Bonin, M, Wilbertz, J, Horn, S, Nguyen, HP, Kuhn, M, Chanarat, S, Wolburg, H, Van der Linden, A & Riess, O 2007, 'Overexpression of human wildtype torsinA and human ¿GAG torsinA in a transgenic mouse model causes phenotypic abnormalities', Neurobiology of Disease, vol. 27, no. 2, pp. 190-206. https://doi.org/10.1016/j.nbd.2007.04.015
Grundmann, K. ; Reischmann, B. ; Vanhoutte, G. ; Hübener, J. ; Teismann, P. ; Hauser, T.-K. ; Bonin, M. ; Wilbertz, J. ; Horn, S. ; Nguyen, H. P. ; Kuhn, M. ; Chanarat, S. ; Wolburg, H. ; Van der Linden, A. ; Riess, O. / Overexpression of human wildtype torsinA and human ¿GAG torsinA in a transgenic mouse model causes phenotypic abnormalities. In: Neurobiology of Disease. 2007 ; Vol. 27, No. 2. pp. 190-206.
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AU - Hauser, T.-K.

AU - Bonin, M.

AU - Wilbertz, J.

AU - Horn, S.

AU - Nguyen, H. P.

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AU - Chanarat, S.

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AU - Van der Linden, A.

AU - Riess, O.

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KW - Neurons

KW - Neurotransmitter Agents

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