Citation

Malki K, Du Rietz E, Crusio W, Pain O, Paya-Cano J, Karadaghi RL, Sluyter F, de Boer SF, Sandnabba K, Schalkwyk LC, Asherson P, Tosto MG. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2016; 171(6): 827-838.

Affiliation

Laboratory for Cognitive Investigations and Behavioural Genetics, Tomsk State University, Tomsk, Russia.

Copyright

(Copyright © 2016, John Wiley and Sons)

DOI

10.1002/ajmg.b.32451

PMID

27090961

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.

© 2016 Wiley Periodicals, Inc.

Language: en