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

2020; Cell Press; Volume: 108; Issue: 4 Linguagem: Inglês

10.1016/j.neuron.2020.09.009

1097-4199

Lien Nguyen, Lauren A. Laboissonniere, Shu Guo, Federica Pilotto, Olivier Scheidegger, A Oestmann, Jennetta W. Hammond, Herman Li, Anu Hyysalo, Roosa Peltola, Amrutha Pattamatta, Tao Zu, Merja H. Voutilainen, Harris A. Gelbard, Smita Saxena, Laura P.W. Ranum,

Neurogenetic and Muscular Disorders Research

Mordes et al., 2020Mordes D. Morrison B.M. Ament X.H. Cantrell C. Mok J. Eggan P. Xue C. Wang J.Y. Eggan K. Rothstein J.D. Absence of survival and motor deficits in 500 repeat C9ORF72 BAC mice.Neuron. 2020; 108: 775-783Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar did not detect the survival or motor phenotypes in C9orf72 BAC transgenic mice originally described by Liu et al., 2016Liu Y. Pattamatta A. Zu T. Reid T. Bardhi O. Borchelt D.R. Yachnis A.T. Ranum L.P. C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD.Neuron. 2016; 90: 521-534Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar. 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., 2020Nguyen L. Montrasio F. Pattamatta A. Tusi S.K. Bardhi O. Meyer K.D. Hayes L. Nakamura K. Banez-Coronel M. Coyne A. et al.Antibody Therapy Targeting RAN Proteins Rescues C9 ALS/FTD Phenotypes in C9orf72 Mouse Model.Neuron. 2020; 105: 645-662.e11Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar 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., 2016Liu Y. Pattamatta A. Zu T. Reid T. Bardhi O. Borchelt D.R. Yachnis A.T. Ranum L.P. C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD.Neuron. 2016; 90: 521-534Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar. 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., 2020Mordes D. Morrison B.M. Ament X.H. Cantrell C. Mok J. Eggan P. Xue C. Wang J.Y. Eggan K. Rothstein J.D. Absence of survival and motor deficits in 500 repeat C9ORF72 BAC mice.Neuron. 2020; 108: 775-783Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Matters Arising paper, published concurrently in Neuron.