biostudies-literatureOng-Palsson EDeutsche ForschungsgemeinschaftMedical Research CouncilNational Health and Medical Research CouncilDeutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) in der Helmholtz-GemeinschaftFederal Ministry BMBF1183-1198https://www.ebi.ac.uk/biostudies/studies/S-EPMC8857007biostudies-literatureUnknown59(2)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 system may contribute to the phenotypes observed. In summary, our study establishes physiological functioMolecular neurobiologyThe β-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice.PMC88570071058672EXC 2145 SyNergy- ID 390857198Dementia Research Development FellowshipMR/S017003/1UKDRI-1010CLINSPECT-M1140050EXC 2145 SyNergy– ID 390857198Hartmann JLichtenthaler SFNjavro JROng-Palsson EPigoni MSchmidt ABusche MAMuller SAWilson YMeyer MMunro KMGunnersen JMfalseThe β-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice.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 system may contribute to the phenotypes observed. In summary, our study establishes physiological functio2022-01-01T00:00:00Z2022 Feb2025-06-01T04:19:54.338Z2025-06-01T04:19:54.338ZS-EPMC88570073495845110.1007/s12035-021-02660-y