Absence of Survival and Motor Deficits in 500 Repeat C9ORF72 BAC Mice
| Autor: | Christopher Cantrell, Daniel A. Mordes, Brett M. Morrison, Jin Yuan Wang, Pierce Eggan, Xanthe H. Ament, Joanie Mok, Kevin Eggan, Carolyn Xue, Jeffrey D. Rothstein |
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| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Neuron. 108:775-783.e4 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2020.08.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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