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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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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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)
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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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DOI: https://doi.org/10.1038/ng1661
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