title: Comparative mRNA analysis of behavioral and genetic mouse models of aggression.
abstract: 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.
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
authors.forename: Karim
authors.initials: K
authors.lastname: Malki
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.|Laboratory for Cognitive Investigations and Behavioral Genetics, Tomsk State University, Tomsk, Russia.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Tosto
authors.affiliation: Centre for Brain and Cognitive Development, Birkbeck, University of London, London, United Kingdom.|Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pain
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
authors.forename: Frans
authors.initials: F
authors.lastname: Sluyter
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut.
authors.forename: Yann S
authors.initials: YS
authors.lastname: Mineur
authors.affiliation: Aquitaine Institute for Cognitive and Integrative Neuroscience, University of Bordeaux, Bordeaux, France.|CNRS, Aquitaine Institute for Cognitive and Integrative Neuroscience, Bordeaux, France.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Crusio
authors.affiliation: Groningen Institute for Evolutionary LifeSciences (GELIFES), University of Groningen, Groningen, The Netherlands.
authors.forename: Sietse
authors.initials: S
authors.lastname: de Boer
authors.affiliation: Faculty of Arts, Psychology and Theology, Åbo Akademi University, Turku, Finland.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Sandnabba
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
authors.forename: Jad
authors.initials: J
authors.lastname: Kesserwani
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
authors.forename: Edward
authors.initials: E
authors.lastname: Robinson
authors.affiliation: School of Biological Sciences, University of Essex, Colchester, United Kingdom.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Schalkwyk
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
mesh_terms: D000374:Aggression / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D053263:Gene Regulatory Networks; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D012333:RNA, Messenger
keywords: BALB/c; aggression; mouse; transcriptomics