The β-Secretase Substrate Seizure 6–Like Protein (SEZ6L) Controls Motor Functions in Mice

E Ong-Pålsson; JR Njavro; Y Wilson; M Pigoni; A Schmidt; SA Müller; M Meyer; J Hartmann; MA Busche; JM Gunnersen; KM Munro; SF Lichtenthaler

Journal article

The β-Secretase Substrate Seizure 6–Like Protein (SEZ6L) Controls Motor Functions in Mice

E Ong-Pålsson, JR Njavro, Y Wilson, M Pigoni, A Schmidt, SA Müller, M Meyer, J Hartmann, MA Busche, JM Gunnersen, KM Munro, SF Lichtenthaler

Molecular Neurobiology | SPRINGER | Published : 2022

DOI: 10.1007/s12035-021-02660-y

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Abstract

The membrane protein seizure 6–like (SEZ6L) is a neuronal substrate of the Alzheimer’s disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous syste..

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University of Melbourne Researchers

Jenny Gunnersen Author

Kathryn Munro Author

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Awarded by BrightFocus Foundation

Funding Acknowledgements

Open Access funding enabled and organized by Projekt DEAL. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy-ID 390857198) and by the Federal Ministry BMBF through grant CLINSPECT-M. This work was also funded by NHMRC Project Grants 1058672 and 1140050 to JMG. KMM is supported by an NHMRC-Australian Research Council (ARC) Dementia Research Development Fellowship. Research collaboration, particularly student and post-doctoral exchange, was funded by Universities Australia (UA)-Deutsche Akademischer Austauschdienst (DAAD) grants to SFL, JMG and KMM. JH and MAB are supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the Medical Research Council, Alzheimer's Society and Alzheimer Research UK. MAB is further supported by a UKRI Future Leaders Fellowship (Grant Number: MR/S017003/1) and acknowledges the donors of Alzheimer's Disease Research (ADR), a program of BrightFocus Foundation (Grant Number: A2019112S).