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

Neuron. 2020 Nov 25;108(4):784-796.e3. doi: 10.1016/j.neuron.2020.09.009. Epub 2020 Oct 5.


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.

Keywords: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis* / genetics
  • Animals
  • C9orf72 Protein / genetics
  • DNA Repeat Expansion
  • Disease Models, Animal
  • Frontotemporal Dementia* / genetics
  • Mice
  • Mice, Transgenic
  • Phenotype


  • C9orf72 Protein

Supplementary concepts

  • Amyotrophic Lateral Sclerosis 2, Juvenile