Survival and Motor Phenotypes in FVB C9-500 ALS/FTD BAC Transgenic Mice Reproduced by Multiple Labs

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.