Absence of Survival and Motor Deficits in 500 Repeat C9ORF72 BAC Mice.

Autor:	Mordes DA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA., Morrison BM; Department of Neurology, The Johns Hopkins University, Baltimore, MD 21205, USA., Ament XH; Department of Neurology, The Johns Hopkins University, Baltimore, MD 21205, USA., Cantrell C; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Mok J; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Eggan P; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Xue C; Department of Neurology, The Johns Hopkins University, Baltimore, MD 21205, USA., Wang JY; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Eggan K; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: eggan@mcb.harvard.edu., Rothstein JD; Department of Neurology, The Johns Hopkins University, Baltimore, MD 21205, USA; Brain Science Institute, The Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: jrothstein@jhmi.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2020 Nov 25; Vol. 108 (4), pp. 775-783.e4. Date of Electronic Publication: 2020 Oct 05.
DOI:	10.1016/j.neuron.2020.08.009
Abstrakt:	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. Competing Interests: Declaration of Interests K.E. is a founder and scientific adviser to Q-state Biosciences, Enclear Therapeutics, and Quarlis. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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