@article{48657289103448dba56c0ed1f279fe63,
title = "A tecpr2 knockout mouse exhibits age-dependent neuroaxonal dystrophy associated with autophagosome accumulation",
abstract = "Mutations in the coding sequence of human TECPR2 were recently linked to spastic paraplegia type 49 (SPG49), a hereditary neurodegenerative disorder involving intellectual disability, autonomic-sensory neuropathy, chronic respiratory disease and decreased pain sensitivity. Here, we report the generation of a novel CRISPR-Cas9 tecpr2 knockout (tecpr2 −/−) mouse that exhibits behavioral pathologies observed in SPG49 patients. tecpr2 −/− mice develop neurodegenerative patterns in an age-dependent manner, manifested predominantly as neuroaxonal dystrophy in the gracile (GrN) and cuneate nuclei (CuN) of the medulla oblongata in the brainstem and dorsal white matter column of the spinal cord. Age-dependent correlation with accumulation of autophagosomes suggests compromised targeting to lysosome. Taken together, our findings establish the tecpr2 knockout mouse as a potential model for SPG49 and ascribe a new role to TECPR2 in macroautophagy/autophagy-related neurodegenerative disorders.",
keywords = "Autophagy, SPG49, TECPR2, axonal dystrophy, lysosome, neurodegeneration",
author = "Tamim-Yecheskel, {Bat Chen} and Milana Fraiberg and Kamilya Kokabi and Saskia Freud and Oren Shatz and Letizia Marvaldi and Nemanja Subic and Ori Brenner and Michael Tsoory and Raya Eilam-Altstadter and Inbal Biton and Alon Savidor and Nili Dezorella and Gali Heimer and Christian Behrends and Bruria Ben-Zeev and Zvulun Elazar",
note = "Funding Information: Z.E. is the incumbent of the Harold Korda Chair of Biology. We are grateful for funding from the Israel Science Foundation (Grant #215/19), the Sagol Longevity Foundation, Joint NRF - ISF Research Fund (Grant #3221/19), and the Yeda-Sela Center for Basic Research. Z. E. and N.S. are supported by a Marie Sk{\l}odowska-Curie ETN grant under the European Union{\textquoteright}s Horizon 2020 Research and Innovation Programme (Grant Agreement No 765912 DRIVE). M.T. is the incumbent of the Carolito Stiftung Research Fellow Chair in Neurodegenerative Diseases C.B. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) within the frameworks of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), the Collaborative Research Center 1177 (ID 259130777) as well as the research grant BE 4685/7-1. Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft [390857198]; H2020 Marie Sk{\l}odowska-Curie Actions [765912]; H2020 Marie Sk{\l}odowska-Curie Actions [765912]; Israel Science Foundation [215/19]; Israel Science Foundation [3221/19]; Collaborative Research Center 1177 [259130777]. Z.E. is the incumbent of the Harold Korda Chair of Biology. We are grateful for funding from the Israel Science Foundation (Grant #215/19), the Sagol Longevity Foundation, Joint NRF - ISF Research Fund (Grant #3221/19), and the Yeda-Sela Center for Basic Research. Z. E. and N.S. are supported by a Marie Sk{\l}odowska-Curie ETN grant under the European Union{\textquoteright}s Horizon 2020 Research and Innovation Programme (Grant Agreement No 765912 DRIVE). M.T. is the incumbent of the Carolito Stiftung Research Fellow Chair in Neurodegenerative Diseases C.B. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) within the frameworks of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy–ID 390857198), the Collaborative Research Center 1177 (ID 259130777) as well as the research grant BE 4685/7-1. The authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2020 Informa UK Limited, trading as Taylor & Francis Group.",
year = "2021",
month = jan,
day = "1",
doi = "10.1080/15548627.2020.1852724",
language = "English",
volume = "17",
pages = "3082--3095",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "10",
}
