Survival and Motor Phenotypes in FVB C9-500 ALS/FTD BAC Transgenic Mice Reproduced by Multiple Labs.
- Nguyen L Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
- Laboissonniere LA Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
- Guo S Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
- Pilotto F Department of Neurology, Inselspital University Hospital Bern, 3010 Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
- Scheidegger O Department of Neurology, Inselspital University Hospital Bern, 3010 Bern, Switzerland.
- Oestmann A Department of Neurology, Inselspital University Hospital Bern, 3010 Bern, Switzerland.
- Hammond JW Center for Neurotherapeutics Discovery, Departments of Neurology, Pediatrics, Neuroscience, and Microbiology and Immunology, University of Rochester, Rochester, NY 14618, USA.
- Li H Center for Neurotherapeutics Discovery, Departments of Neurology, Pediatrics, Neuroscience, and Microbiology and Immunology, University of Rochester, Rochester, NY 14618, USA.
- Hyysalo A Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.
- Peltola R Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.
- Pattamatta A Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
- Zu T Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
- Voutilainen MH Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland.
- Gelbard HA Center for Neurotherapeutics Discovery, Departments of Neurology, Pediatrics, Neuroscience, and Microbiology and Immunology, University of Rochester, Rochester, NY 14618, USA.
- Saxena S Department of Neurology, Inselspital University Hospital Bern, 3010 Bern, Switzerland.
- Ranum LPW Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, Genetics Institute, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, Norman Fixel Institute for Neurological Disease, University of Florida, Gainesville, FL 32610, USA. Electronic address: ranum@ufl.edu.
- 2020-10-06
Published in:
- Neuron. - 2020
ALS/FTD
C9orf72
FVB strain background
RAN proteins
microsatellite repeat
motor neuron disease
repeat associated non-AUG (RAN) translation
repeat expansion mutation
seizures
transgenic mouse models
English
Mordes et al. (2020) did not detect the survival or motor phenotypes in C9orf72 BAC transgenic mice originally described by Liu et al. (2016). We discuss methodological differences between the Mordes and Liu studies, several additional studies in which survival and motor phenotypes were found, and possible environmental and genetic effects. First, Nguyen et al. (2020) showed robust ALS/FTD phenotypes in C9-BAC versus non-transgenic (NT) mice and that α-GA1 treatment improved survival, behavior, and neurodegeneration. The groups of Gelbard and Saxena also show decreased survival of C9-BAC versus NT mice and neuropathological and behavioral deficits similar to those shown by Liu et al. (2016). Although FVB/N mice can have seizures, increases in seizure severity and death of C9 and NT animals, which may mask C9 disease phenotypes, have been observed in recent C9-500 FVB/NJ-bred cohorts. In summary, we provide an update on phenotypes seen in FVB C9-BAC mice and additional details to successfully use this model. This Matters Arising Response paper addresses the Mordes et al. (2020) Matters Arising paper, published concurrently in Neuron.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1016/j.neuron.2020.09.009
- PMID 33022226
- Persistent URL
- https://sonar.ch/global/documents/47278
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