Related Experiment Video
Updated: Dec 6, 2025
Low-Cost Gait Analysis for Behavioral Phenotyping of Mouse Models of Neuromuscular Disease
Published on: July 18, 2019
Survival and Motor Phenotypes in FVB C9-500 ALS/FTD BAC Transgenic Mice Reproduced by Multiple Labs
Lien Nguyen1, Lauren A Laboissonniere1, Shu Guo1
1Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
Abstract:
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.
Insights
This study clarifies conflicting findings regarding C9orf72 BAC transgenic mouse models for ALS/FTD. It highlights methodological differences and confirms motor and survival phenotypes in these crucial models.
Area of Science:
- Neuroscience
- Genetics
- Animal Models
Background:
- Conflicting reports exist on the C9orf72 BAC transgenic mouse model's utility for studying Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).
- Mordes et al. (2020) reported a lack of survival and motor phenotypes, contrasting with earlier findings by Liu et al. (2016).
Purpose of the Study:
- To address discrepancies in the observed phenotypes of C9orf72 BAC transgenic mice.
- To provide an updated understanding of the phenotypes in FVB C9-BAC mice.
- To offer guidance for the successful utilization of this mouse model.
Main Methods:
- Comparative analysis of methodological differences between conflicting studies.
- Review of additional studies reporting survival and motor phenotypes.
- Investigation of potential environmental and genetic factors influencing observed phenotypes.
Main Results:
- Nguyen et al. (2020) demonstrated robust ALS/FTD phenotypes and therapeutic benefits of α-GA1 treatment in C9-BAC mice.
- Other research groups (Gelbard, Saxena) also reported decreased survival and neuropathological/behavioral deficits in C9-BAC mice.
- Seizure severity and mortality in FVB/NJ-bred cohorts may confound phenotype observation.
Conclusions:
- The C9orf72 BAC transgenic mouse model exhibits relevant survival and motor phenotypes for ALS/FTD research.
- Methodological variations and genetic background (e.g., FVB/NJ) can impact phenotype expression.
- This model remains valuable for investigating ALS/FTD pathogenesis and therapeutic strategies.
