role of abca7 in mouse behaviours relevant to neurodegenerative diseasesabca7在鼠标行为神经退行性疾病有关.pdfVIP

Role of Abca7 in Mouse Behaviours Relevant to Neurodegenerative Diseases Warren Logge1,2., David Cheng1,3., Rose Chesworth1,2, Surabhi Bhatia1,3, Brett Garner1,4,5, Woojin Scott Kim1,3, Tim Karl1,2,3,6* 1 Neuroscience Research Australia, Randwick, Australia, 2 Schizophrenia Research Institute, Darlinghurst, Australia, 3 School of Medical Sciences, University of New South Wales, New South Wales, Australia, 4 Illawarra Health and Medical Research Institute, University of Wollongong, New South Wales, Australia, 5 School of Biological Sciences, University of Wollongong, New South Wales, Australia, 6 School of Psychology, University of New South Wales, New South Wales, Australia Abstract ATP-binding cassette transporters of the subfamily A (ABCA) are responsible for the translocation of lipids including cholesterol, which is crucial for neurological function. Recent studies suggest that the ABC transporter ABCA7 may play a role in the development of brain disorders such as schizophrenia and Alzheimer’s disease. However, Abca7’s role in cognition and other behaviours has not been investigated. Therefore, we characterised homozygous Abca7 knockout mice in a battery of tests for baseline behaviours (i.e. physical exam, baseline locomotion and anxiety) and behaviours relevant to schizophrenia (i.e. prepulse inhibition and locomotor response to psychotropic drugs) and Alzheimer’s disease (i.e. cognitive domains). Knockout mice had normal motor functions and sensory abilities and performed the same as wild type-like animals in anxiety tasks. Short-term spatial memory and fear-associated learning was also intact in Abca7 knockout mice. However, male knockout mice exhibited significantly impaired novel object recognition memory. Task acquisition was unaffected in the cheeseboard task. Female mice exhibited impa