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Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse

Nature Genetics volume 37, pages 1213–1215 (2005)Cite this article

Abstract

Vacuolar-vesicular protein sorting (Vps) factors are involved in vesicular trafficking in eukaryotic cells. We identified the missense mutation L967Q in Vps54 in the wobbler mouse, an animal model of amyotrophic lateral sclerosis, and also characterized a lethal allele, Vps54β-geo. Motoneuron survival and spermiogenesis are severely compromised in the wobbler mouse, indicating that Vps54 has an essential role in these processes.

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Figure 1: Positional cloning of the gene underlying the wr mutation.
Figure 2: Transgenic rescue of the wobbler phenotype and noncomplementation of a gene-trap allele of Vps54.

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Acknowledgements

We thank G. Gavrilina, M. Ebel, W. Müller and M. Augustin for assistance and Transgenic Animal Model Core of the University of Michigan's Biomedical Research Core Facilities, Center for Organogenesis, US National Institutes of Health, BayGenomics, Ingenium Pharmaceuticals AG, Martinsried, Deutsche Forschungsgemeinschaft, Volkswagenstiftung, Fonds der Chemischen Industrieand NRW International Graduate School in Bioinformatics and Genome Research for financial support.

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Author notes

  1. Thomas Schmitt-John

    Present address: Department of Molecular Biology, University of Aarhus, Denmark

Authors and Affiliations

  1. Developmental Biology and Molecular Pathology, Bielefeld University, Germany

    Thomas Schmitt-John, Carsten Drepper, Anke Mußmann, Phillip Hahn, Melanie Kuhlmann, Cora Thiel, Peter Heimann & Harald Jockusch

  2. Research Group Infection Genetics, German Research Center for Biotechnology, Braunschweig, Germany

    Phillip Hahn & Andreas Lengeling

  3. Department of Experimental Immunology, German Research Center for Biotechnology, Braunschweig, Germany

    Martin Hafner

  4. Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA

    Julie M Jones & Miriam H Meisler

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  1. Thomas Schmitt-John
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  2. Carsten Drepper
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Corresponding author

Correspondence to Thomas Schmitt-John.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Rescue of wobbler mutants with the BAC transgene containing Vps54. (PDF 414 kb)

Supplementary Fig. 2

Characterization of the Vps54β-geo gene trap allele. (PDF 217 kb)

Supplementary Fig. 3

Phenotype analysis of Vps54β-geo/β-geo gene trap embryos. (PDF 842 kb)

Supplementary Methods (PDF 24 kb)

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Schmitt-John, T., Drepper, C., Mußmann, A. et al. Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse. Nat Genet 37, 1213–1215 (2005). https://doi.org/10.1038/ng1661

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