Back to Search
Start Over
Absence of Survival and Motor Deficits in 500 Repeat C9ORF72 BAC Mice
- Source :
- Neuron. 108:775-783.e4
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Summary A hexanucleotide repeat expansion at C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Initial studies of bacterial artificial chromosome (BAC) transgenic mice harboring this expansion described an absence of motor and survival phenotypes. However, a recent study by Liu and colleagues described transgenic mice harboring a large repeat expansion (C9-500) and reported decreased survival and progressive motor phenotypes. To determine the utility of the C9-500 animals for understanding degenerative mechanisms, we validated and established two independent colonies of transgene carriers. However, extended studies of these animals for up to 1 year revealed no reproducible abnormalities in survival, motor function, or neurodegeneration. Here, we propose several potential explanations for the disparate nature of our findings from those of Liu and colleagues. Resolving the discrepancies we identify will be essential to settle the translational utility of C9-500 mice. This Matters Arising paper is in response to Liu et al. (2016) , published in Neuron. See also the response by Nguyen et al. (2020), published in this issue.
- Subjects :
- Male
0301 basic medicine
Genetically modified mouse
Heterozygote
Survival
Transgene
Mice, Transgenic
Biology
Mice
03 medical and health sciences
0302 clinical medicine
C9orf72
medicine
Animals
Amyotrophic lateral sclerosis
Genetics
Bacterial artificial chromosome
DNA Repeat Expansion
C9orf72 Protein
General Neuroscience
Amyotrophic Lateral Sclerosis
Neurodegeneration
medicine.disease
Disease Models, Animal
Phenotype
030104 developmental biology
Motor Skills
Nerve Degeneration
Trinucleotide repeat expansion
030217 neurology & neurosurgery
Frontotemporal dementia
Subjects
Details
- ISSN :
- 08966273
- Volume :
- 108
- Database :
- OpenAIRE
- Journal :
- Neuron
- Accession number :
- edsair.doi.dedup.....853b0ddf3f9b12f4190b228d06a383ff