@article{e0b0bf0d542446d7940ef20053fd18df,
title = "The Loss of TBK1 Kinase Activity in Motor Neurons or in All Cell Types Differentially Impacts ALS Disease Progression in SOD1 Mice",
abstract = "DNA sequence variants in the TBK1 gene associate with familial and sporadic ALS. Gerbino et al. show that partial or complete loss-of-function TBK1 mutations alone do not induce neurodegeneration in mice. However, they profoundly affect disease onset and progression in the SOD1 ALS mouse model.",
keywords = "ALS, Amyotrophic Lateral Sclerosis, glia, interferon response, motor neuron autophagy, neuroinflammation, selective autophagy, SOD1 mouse model, TBK1",
author = "Valeria Gerbino and Esther Kaunga and Junqiang Ye and Daniele Canzio and Sean O'Keeffe and Rudnick, {Noam D.} and Paolo Guarnieri and Lutz, {Cathleen M.} and Tom Maniatis",
note = "Funding Information: We thank Drs. Isaac Chiu, Stavros Lomvardas, David Hirsh, and Joseph Puccini for their critical reading of the manuscript. We would also like to thank Dr. Ai Yamamoto for helpful discussion and Dr. Frank Baas for providing patient fibroblasts. We thank Emily Birnbaum and Chris Griffey for technical help. This work was supported by grants from Project ALS (PRALS 2017-09) and Takeda Pharmaceuticals (1000344702). V.G. is a recipient of a Milton Safenowitz postdoctoral fellowship from ALSA, and D.C. is a recipient of an NIH Path to Independence Award K99/R00 K99GM121815. The generation and development of the CRISPR/Cas9 mutant mouse models was supported by the Jackson Laboratory Precision Genetics Center Grant U54OD020351-04. We acknowledge the support of Aamir Zuberi (Jackson Laboratory) and of The Jackson Laboratory Genome Engineering Technology group. Jackson Lab Core facility costs were defrayed by Cancer Center Support Grant CA034196. V.G. and T.M. designed the project; V.G, E.K. J.Y. D.C. and N.D.R. performed experiments; V.G. and E.K. analyzed data; V.G. D.C. S.O.K. and P.G. analyzed sequencing data; C.M.L. generated mutant mice; V.G. and T.M. wrote the manuscript; and J.Y. and N.D.R provided critical comments. The authors declare no competing interests. Funding Information: We thank Drs. Isaac Chiu, Stavros Lomvardas, David Hirsh, and Joseph Puccini for their critical reading of the manuscript. We would also like to thank Dr. Ai Yamamoto for helpful discussion and Dr. Frank Baas for providing patient fibroblasts. We thank Emily Birnbaum and Chris Griffey for technical help. This work was supported by grants from Project ALS ( PRALS 2017-09 ) and Takeda Pharmaceuticals ( 1000344702 ). V.G. is a recipient of a Milton Safenowitz postdoctoral fellowship from ALSA , and D.C. is a recipient of an NIH Path to Independence Award K99/R00 K99GM121815 . The generation and development of the CRISPR/Cas9 mutant mouse models was supported by the Jackson Laboratory Precision Genetics Center Grant U54OD020351-04. We acknowledge the support of Aamir Zuberi (Jackson Laboratory) and of The Jackson Laboratory Genome Engineering Technology group. Jackson Lab Core facility costs were defrayed by Cancer Center Support Grant CA034196 . Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = jun,
day = "3",
doi = "10.1016/j.neuron.2020.03.005",
language = "English (US)",
volume = "106",
pages = "789--805.e5",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",
}