Journal article

Lack of Sez6 Family Proteins Impairs Motor Functions, Short-Term Memory, and Cognitive Flexibility and Alters Dendritic Spine Properties

Amelia Nash, Timothy D Aumann, Martina Pigoni, Stefan F Lichtenthaler, Hiroshi Takeshima, Kathryn M Munro, Jenny M Gunnersen



Seizure-related gene 6 (Sez6), Sez6-Like (Sez6L), and Sez6-Like 2 (Sez6L2) comprise a family of homologous proteins widely expressed throughout the brain that have been linked to neurodevelopmental and psychiatric disorders. Here, we use Sez6 triple knockout (TKO) mice, which lack all three Sez6 family proteins, to demonstrate that Sez6 family proteins regulate dendritic spine structure and cognitive functions, motor learning, and maintenance of motor functions across the lifespan. Compared to WT controls, we found that Sez6 TKO mice had impaired motor learning and their motor coordination was negatively affected from 6 weeks old and declined more rapidly as they aged. Sez6 TKO mice had redu..

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Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by Deutsche Forschungsgemeinschaft (German Research Foundation)

Funding Acknowledgements

National Health and Medical Research Council (NHMRC) of Australia project (grant no. 1058672 to J.M.G.); NHMRC-Australian Research Council (ARC) Dementia Research Development Fellowship (K.M.M); Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of theMunich Cluster for Systems Neurology (EXC 2145 SyNergy to S.F.L.).