The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans

dc.contributor.authorQiu, Bin
dc.contributor.authorLuczak, Susan E.
dc.contributor.authorWall, Tamara L.
dc.contributor.authorXu, Yuxue
dc.contributor.authorEng, Mimy Y.
dc.contributor.authorSteward, Robert B.
dc.contributor.authorShou, Weinian
dc.contributor.authorBoehm II, Stephen L.
dc.contributor.authorChester, Julia A.
dc.contributor.authorYong, Weidong
dc.contributor.authorLiang, Tiebing
dc.contributor.authorKirchhoff, Aaron M.
dc.contributor.departmentDepartment of Psychology, School of Scienceen_US
dc.date.accessioned2017-05-23T18:48:40Z
dc.date.available2017-05-23T18:48:40Z
dc.date.issued2016-08
dc.description.abstractFKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.en_US
dc.identifier.citationQiu, B., Luczak, S. E., Wall, T. L., Kirchhoff, A. M., Xu, Y., Eng, M. Y., … Liang, T. (2016). The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans. International Journal of Molecular Sciences, 17(8), 1271. http://doi.org/10.3390/ijms17081271en_US
dc.identifier.urihttps://hdl.handle.net/1805/12692
dc.language.isoen_USen_US
dc.publisherMDPIen_US
dc.relation.isversionof10.3390/ijms17081271en_US
dc.relation.journalInternational Journal of Molecular Sciencesen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/
dc.sourcePMCen_US
dc.subjectFkbp5 knockouten_US
dc.subjectAlcohol drinking behavioren_US
dc.subjectHuman alcohol use disorderen_US
dc.titleThe FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humansen_US
dc.typeArticleen_US
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