title: Transcriptome analysis of genes and gene networks involved in aggressive behavior in mouse and zebrafish.
abstract: Despite moderate heritability estimates, the molecular architecture of aggressive behavior remains poorly characterized. This study compared gene expression profiles from a genetic mouse model of aggression with zebrafish, an animal model traditionally used to study aggression. A meta-analytic, cross-species approach was used to identify genomic variants associated with aggressive behavior. The Rankprod algorithm was used to evaluated mRNA differences from prefrontal cortex tissues of three sets of mouse lines (N = 18) selectively bred for low and high aggressive behavior (SAL/LAL, TA/TNA, and NC900/NC100). The same approach was used to evaluate mRNA differences in zebrafish (N = 12) exposed to aggressive or non-aggressive social encounters. Results were compared to uncover genes consistently implicated in aggression across both studies. Seventy-six genes were differentially expressed (PFP < 0.05) in aggressive compared to non-aggressive mice. Seventy genes were differentially expressed in zebrafish exposed to a fight encounter compared to isolated zebrafish. Seven genes (Fos, Dusp1, Hdac4, Ier2, Bdnf, Btg2, and Nr4a1) were differentially expressed across both species 5 of which belonging to a gene-network centred on the c-Fos gene hub. Network analysis revealed an association with the MAPK signaling cascade. In human studies HDAC4 haploinsufficiency is a key genetic mechanism associated with brachydactyly mental retardation syndrome (BDMR), which is associated with aggressive behaviors. Moreover, the HDAC4 receptor is a drug target for valproic acid, which is being employed as an effective pharmacological treatment for aggressive behavior in geriatric, psychiatric, and brain-injury patients. © 2016 Wiley Periodicals, Inc.
authors.affiliation: King's College London, Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, Psychology and Neuroscience, United Kingdom.
authors.forename: Karim
authors.initials: K
authors.lastname: Malki
authors.affiliation: King's College London, Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, Psychology and Neuroscience, United Kingdom.
authors.forename: Ebba
authors.initials: E
authors.lastname: Du Rietz
authors.affiliation: University of Bordeaux, Aquitaine Institute for Cognitive and Integrative Neuroscience, Bordeaux, France.|CNRS, Aquitaine Institute for Cognitive and Integrative Neuroscience, Bordeaux, France.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Crusio
authors.affiliation: Centre of Brain and Cognitive Development, Birkbeck, University of 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, Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, Psychology and Neuroscience, United Kingdom.
authors.forename: Jose
authors.initials: J
authors.lastname: Paya-Cano
authors.affiliation: King's College London, Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, Psychology and Neuroscience, United Kingdom.
authors.forename: Rezhaw L
authors.initials: RL
authors.lastname: Karadaghi
authors.affiliation: King's College London, Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, Psychology and Neuroscience, United Kingdom.
authors.forename: Frans
authors.initials: F
authors.lastname: Sluyter
authors.affiliation: Groningen Institute for Evolutionary LifeSciences (GELIFES), University of Groningen, Groningen, The Netherlands.
authors.forename: Sietse F
authors.initials: SF
authors.lastname: de Boer
authors.affiliation: Faculty of Arts, Psychology and Theology, Åbo Akademi University, Turku, Finland.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Sandnabba
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, Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, Psychology and Neuroscience, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
authors.affiliation: King's College London, Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, Psychology and Neuroscience, United Kingdom.|Laboratory for Cognitive Investigations and Behavioural Genetics, Tomsk State University, Tomsk, Russia.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tosto
mesh_terms: D000374:Aggression / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics; D016762:Genes, fos / Q000235:genetics / Q000502:physiology; D051379:Mice; D012919:Social Behavior; D059467:Transcriptome / Q000235:genetics; D015027:Zebrafish / Q000235:genetics
keywords: NC900/NC100; RankProd; SAL/LAL; TA/TNA; aggression