Role of Abca7 in mouse behaviours relevant to neurodegenerative diseases

• Published in: PloS one Vol. 7; no. 9; p. e45959
• Main Authors: Logge, Warren, Cheng, David, Chesworth, Rose, Bhatia, Surabhi, Garner, Brett, Kim, Woojin Scott, Karl, Tim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.09.2012; Public Library of Science (PLoS)
• Subjects: ABC transporter; Acoustic startle response; Alzheimer's disease; Animals; Anxiety; Anxiety - genetics; Anxiety - metabolism; Anxiety - physiopathology; Apoptosis; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; ATP-binding protein; Biology; Brain; Brain research; Carrier proteins; Cholesterol; Cognition; Cognition & reasoning; Cognitive ability; Development and progression; Dizocilpine; Drugs; Fear; Female; Gene Knockout Techniques; Genetic aspects; Homeostasis; Lipids; Locomotion; Male; Medicine; Memory; Memory tasks; Mental disorders; Mental task performance; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - physiopathology; Neurodevelopmental disorders; Neurological diseases; Neurosciences; Object recognition; Pattern recognition; Physiological aspects; Psychopharmacology; Psychotropic drugs; Rodents; Schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; Schizophrenia - physiopathology; Sensorimotor gating; Sensory Gating; Spatial analysis; Spatial discrimination learning; Spatial memory; Startle response; Translocation; Australia; New South Wales Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045959

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 impaired spatial reference memory. This phenomenon was more pronounced in female Abca7 null mice. Acoustic startle response, sensorimotor gating and baseline locomotion was unaltered in Abca7 knockout mice. Female knockouts showed a moderately increased motor response to MK-801 than control mice. In conclusion, Abca7 appears to play only a minor role in behavioural domains with a subtle sex-specific impact on particular cognitive domains.