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Proc Biol Sci. 2018 Jun 13;285(1880). pii: 20180294. doi: 10.1098/rspb.2018.0294.

Experiential contributions to social dominance in a rat model of fragile-X syndrome.

Saxena K1,2,3,4,5, Webster J4, Hallas-Potts A4, Mackenzie R4, Spooner PA3,4, Thomson D3,4, Kind P1,2,3,5, Chatterji S1,2,3,5,6, Morris RGM7,2,3,4,5.

Author information

1
Simons Initiative for the Developing Brain, Edinburgh Neuroscience, 1 George Square, Edinburgh EH8 9JZ, UK.
2
The Patrick Wild Centre, Edinburgh Neuroscience, 1 George Square, Edinburgh EH8 9JZ, UK.
3
Centre for Discovery Brain Sciences, Edinburgh Neuroscience, 1 George Square, Edinburgh EH8 9JZ, UK.
4
Centre for Cognitive and Neural Systems, Edinburgh Neuroscience, 1 George Square, Edinburgh EH8 9JZ, UK.
5
Centre for Brain Development and Repair, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, 560065, India.
6
National Centre for Biological Sciences, Bangalore, 560065, India.
7
Simons Initiative for the Developing Brain, Edinburgh Neuroscience, 1 George Square, Edinburgh EH8 9JZ, UK r.g.m.morris@ed.ac.uk.

Abstract

Social withdrawal is one phenotypic feature of the monogenic neurodevelopmental disorder fragile-X. Using a 'knockout' rat model of fragile-X, we examined whether deletion of the Fmr1 gene that causes this condition would affect the ability to form and express a social hierarchy as measured in a tube test. Male fragile-X 'knockout' rats living together could successfully form a social dominance hierarchy, but were significantly subordinate to wild-type animals in mixed group cages. Over 10 days of repeated testing, the fragile-X mutant rats gradually showed greater variance and instability of rank during their tube-test encounters. This affected the outcome of future encounters with stranger animals from other cages, with the initial phenotype of wild-type dominance lost to a more complex picture that reflected, regardless of genotype, the prior experience of winning or losing. Our findings offer a novel insight into the complex dynamics of social interactions between laboratory living groups of fragile-X and wild-type rats. Even though this is a monogenic condition, experience has an impact upon future interactions with other animals. Gene/environment interactions should therefore be considered in the development of therapeutics.

KEYWORDS:

Fmr1; autism-spectrum disorders; fragile-X; gene–environment interactions; hierarchy; social dominance

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