Role of Abca7 in mouse behaviours relevant to neurodegenerative diseases

PLoS One. 2012;7(9):e45959. doi: 10.1371/journal.pone.0045959. Epub 2012 Sep 24.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Anxiety / genetics
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Cognition*
  • Fear
  • Female
  • Gene Knockout Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity*
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Schizophrenia / genetics
  • Schizophrenia / metabolism
  • Schizophrenia / physiopathology
  • Sensory Gating*

Substances

  • ATP-Binding Cassette Transporters
  • Abca7 protein, mouse

Grant support

This research was supported by a project grant to BG from the National Health and Medical Research Council (NHMRC: 510148) and the Schizophrenia Research Institute (SRI) utilizing infrastructure funding from New South Wales Health. TK is supported by a National Health and Medical Research Council Career Development Award (568752), by the National Alliance for Research on Schizophrenia and Depression (Young Investigator Award), and the Motor Neuron Disease Research Institute of Australia. BG is supported by a Fellowship from the Australian Research Council (FT0991986) and is an honorary National Health and Medical Research Council Senior Research Fellow (630445). BG and TK are also supported by a National Health and Medical Research Council project grant (1003886). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.