Inter‐α‐inhibitor deficiency in the mouse is associated with alterations in anxiety‐like behavior, exploration and social approach. (6th August 2018)

• Record Type: Journal Article
• Authors: Goulding, David R.; Nikolova, Viktoriya D.; Mishra, Lopa; Zhuo, Lisheng; Kimata, Koji; McBride, Sandra J.; Moy, Sheryl S.; Harry, G. J.; Garantziotis, Stavros
• Is Part Of: Genes, brain, and behavior. Volume 18:Number 1(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-08-06
• Subjects: Behavior genetics -- Periodicals; Neurogenetics -- Periodicals; 616.8
• DOI: 10.1111/gbb.12505
• Languages: English
• ISSNs: 1601-1848

Abstract

Abstract : In recent years, several genome‐wide association studies have identified candidate regions for genetic susceptibility in major mood disorders. Most notable are regions in a locus in chromosome 3p21, encompassing the genes NEK4‐ITIH1‐ITIH3‐ITIH4 . Three of these genes represent heavy chains of the composite protein inter‐α‐inhibitor (IαI). In order to further establish associations of these genes with mood disorders, we evaluated behavioral phenotypes in mice deficient in either Ambp/bikunin, which is necessary for functional ITIH1 and ITIH3 complexes, or in Itih4, the gene encoding the heavy chain Itih4. We found that loss of Itih4 had no effect on the behaviors tested, but loss of Ambp /bikunin led to increased anxiety‐like behavior in the light/dark and open field tests and reduced exploratory activity in the elevated plus maze, light/dark preference and open field tests. Ambp /bikunin knockout mice also exhibited a sex‐dependent exaggeration of acoustic startle responses, alterations in social approach during a three‐chamber choice test, and an elevated fear conditioning response. These results provide experimental support for the role of ITIH1/ITIH3 in the development of mood disorders. Abstract : Ambp deficient mice have increased anxiety‐like behavior and reduced exploratory activity suggesting gene association with mood disorders.