First behavioural characterisation of a knockout mouse model for the transforming growth factor (TGF)-β superfamily cytokine, MIC-1/GDF15

Low, Jac Kee, Ambikairajah, Ananthan, Shang, Kani, Brown, David A., Tsai, Vicky W. W., Breit, Samuel N. and Karl, Tim 2017, First behavioural characterisation of a knockout mouse model for the transforming growth factor (TGF)-β superfamily cytokine, MIC-1/GDF15, PLOS One, vol. 12, no. 1, pp. 1-14, doi: 10.1371/journal.pone.0168416.


Title First behavioural characterisation of a knockout mouse model for the transforming growth factor (TGF)-β superfamily cytokine, MIC-1/GDF15
Formatted title First behavioural characterisation of a knockout mouse model for the transforming growth factor (TGF)-β superfamily cytokine, MIC-1/GDF15
Author(s) Low, Jac Kee
Ambikairajah, Ananthan
Shang, Kani
Brown, David A.
Tsai, Vicky W. W.
Breit, Samuel N.
Karl, Tim
Journal name PLOS One
Volume number 12
Issue number 1
Article ID e0168416
Start page 1
End page 14
Total pages 14
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2017
ISSN 1932-6203
Keyword(s) Animals
Behavior, Animal
Eating
Exploratory Behavior
Female
Growth Differentiation Factor 15
Male
Mice
Mice, Knockout
Sex Characteristics
Social Behavior
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MACROPHAGE INHIBITORY CYTOKINE-1
NEUREGULIN-1 MUTANT MICE
SOCIAL-INTERACTION TEST
OPEN-FIELD BEHAVIOR
ELEVATED PLUS-MAZE
NEUROPEPTIDE-Y
ANXIETY
RAT
MORTALITY
COGNITION
Summary Macrophage inhibitory cytokine-1 (MIC-1), also known as growth differentiation factor 15 (GDF15), is a stress response cytokine. MIC-1/GDF15 is secreted into the cerebrospinal fluid and increased levels of MIC-1/GDF15 are associated with a variety of diseases including cognitive decline. Furthermore, Mic-1/Gdf15 knockout mice (Mic-1 KO) weigh more, have increased adiposity, associated with increased spontaneous food intake, and exhibit reduced basal energy expenditure and physical activity. The current study was designed to comprehensively determine the role of MIC-1/GDF15 on behavioural domains of male and female knockout mice including locomotion, exploration, anxiety, cognition, social behaviours, and sensorimotor gating. Mic-1 KO mice exhibited a task-dependent increase in locomotion and exploration and reduced anxiety-related behaviours across tests. Spatial working memory and social behaviours were not affected by Mic-1/Gdf15 deficiency. Interestingly, knockout mice formed an increased association with the conditioned stimulus in fear conditioning testing and also displayed significantly improved prepulse inhibition. Overall sex effects were evident for social behaviours, fear conditioning, and sensorimotor gating. This is the first study defining the role of Mic-1/Gdf15 in a number of behavioural domains. Whether the observed impact is based on direct actions of Mic-1/Gdf15 deficiency on the CNS or whether the behavioural effects are mediated by indirect actions on e.g. other neurotransmitter systems must be clarified in future studies.
Language eng
DOI 10.1371/journal.pone.0168416
Field of Research MD Multidisciplinary
Copyright notice ©2017, Low et al.
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30110554

Document type: Journal Article
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