Comparative mRNA analysis of behavioral and genetic mouse models of aggression

Karim Malki, Maria G. Tosto, Oliver Pain, Frans Sluyter, Yann S. Mineur, Wim E. Crusio, Sietse de Boer, Kenneth N. Sandnabba, Jad Kesserwani, Edward Robinson, Leonard C. Schalkwyk, Philip Asherson
Am. J. Med. Genet.. 2016-02-17; 171(3): 427-436
DOI: 10.1002/ajmg.b.32424

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1. Am J Med Genet B Neuropsychiatr Genet. 2016 Apr;171B(3):427-36. doi:
10.1002/ajmg.b.32424. Epub 2016 Feb 17.

Comparative mRNA analysis of behavioral and genetic mouse models of aggression.

Malki K(1), Tosto MG(1)(2), Pain O(3)(4), Sluyter F(1), Mineur YS(5), Crusio
WE(6)(7), de Boer S(8), Sandnabba KN(9), Kesserwani J(1), Robinson E(1),
Schalkwyk LC(10), Asherson P(1).

Author information:
(1)King’s College London, MRC Social, Genetic and Developmental Psychiatry
Centre, Institute of Psychiatry, London, United Kingdom.
(2)Laboratory for Cognitive Investigations and Behavioral Genetics, Tomsk State
University, Tomsk, Russia.
(3)Centre for Brain and Cognitive Development, Birkbeck, University of London,
London, United Kingdom.
(4)Department of Non-Communicable Disease Epidemiology, London School of Hygiene
and Tropical Medicine, London, United Kingdom.
(5)Department of Psychiatry, School of Medicine, Yale University, New Haven,
(6)Aquitaine Institute for Cognitive and Integrative Neuroscience, University of
Bordeaux, Bordeaux, France.
(7)CNRS, Aquitaine Institute for Cognitive and Integrative Neuroscience,
Bordeaux, France.
(8)Groningen Institute for Evolutionary LifeSciences (GELIFES), University of
Groningen, Groningen, The Netherlands.
(9)Faculty of Arts, Psychology and Theology, Åbo Akademi University, Turku,
(10)School of Biological Sciences, University of Essex, Colchester, United

Mouse models of aggression have traditionally compared strains, most notably
BALB/cJ and C57BL/6. However, these strains were not designed to study aggression
despite differences in aggression-related traits and distinct reactivity to
stress. This study evaluated expression of genes differentially regulated in a
stress (behavioral) mouse model of aggression with those from a recent genetic
mouse model aggression. The study used a discovery-replication design using two
independent mRNA studies from mouse brain tissue. The discovery study identified
strain (BALB/cJ and C57BL/6J) × stress (chronic mild stress or control)
interactions. Probe sets differentially regulated in the discovery set were
intersected with those uncovered in the replication study, which evaluated
differences between high and low aggressive animals from three strains
specifically bred to study aggression. Network analysis was conducted on
overlapping genes uncovered across both studies. A significant overlap was found
with the genetic mouse study sharing 1,916 probe sets with the stress model.
Fifty-one probe sets were found to be strongly dysregulated across both studies
mapping to 50 known genes. Network analysis revealed two plausible pathways
including one centered on the UBC gene hub which encodes ubiquitin, a protein
well-known for protein degradation, and another on P38 MAPK. Findings from this
study support the stress model of aggression, which showed remarkable molecular
overlap with a genetic model. The study uncovered a set of candidate genes
including the Erg2 gene, which has previously been implicated in different
psychopathologies. The gene networks uncovered points at a Redox pathway as
potentially being implicated in aggressive related behaviors.

© 2016 Wiley Periodicals, Inc.

DOI: 10.1002/ajmg.b.32424
PMID: 26888158 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus