The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans
FKBP5 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 rol...
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doaj-7a43cea1c070404ba5f4758607d453c62020-11-25T00:38:23ZengMDPI AGInternational Journal of Molecular Sciences1422-00672016-08-01178127110.3390/ijms17081271ijms17081271The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in HumansBin Qiu0Susan E. Luczak1Tamara L. Wall2Aaron M. Kirchhoff3Yuxue Xu4Mimy Y. Eng5Robert B. Stewart6Weinian Shou7Stephen L. Boehm8Julia A. Chester9Weidong Yong10Tiebing Liang11Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing 100021, ChinaDepartment of Psychology, University of Southern California, Los Angeles, CA 90089, USADepartment of Psychiatry, University of California, San Diego, CA 92037, USAImmunology and Microbial Science Department, Research Technician, The Scripps Research Institute, Scripps Clinic South Driveway, La Jolla, CA 92037, USAInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing 100021, ChinaVeterans Medical Research Foundation, San Diego, CA 92161, USADepartment of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USADepartments of Pediatrics and Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Psychological Sciences, Purdue University, West Lafayette, IN 47907, USAInstitute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing 100021, ChinaDepartment of Medicine, Indiana University School of Medicine Gatch Hall, Indianapolis, IN 46202, USAFKBP5 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.http://www.mdpi.com/1422-0067/17/8/1271Fkbp5 knockoutalcohol drinking behaviorhuman alcohol use disorder |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bin Qiu Susan E. Luczak Tamara L. Wall Aaron M. Kirchhoff Yuxue Xu Mimy Y. Eng Robert B. Stewart Weinian Shou Stephen L. Boehm Julia A. Chester Weidong Yong Tiebing Liang |
spellingShingle |
Bin Qiu Susan E. Luczak Tamara L. Wall Aaron M. Kirchhoff Yuxue Xu Mimy Y. Eng Robert B. Stewart Weinian Shou Stephen L. Boehm Julia A. Chester Weidong Yong Tiebing Liang The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans International Journal of Molecular Sciences Fkbp5 knockout alcohol drinking behavior human alcohol use disorder |
author_facet |
Bin Qiu Susan E. Luczak Tamara L. Wall Aaron M. Kirchhoff Yuxue Xu Mimy Y. Eng Robert B. Stewart Weinian Shou Stephen L. Boehm Julia A. Chester Weidong Yong Tiebing Liang |
author_sort |
Bin Qiu |
title |
The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans |
title_short |
The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans |
title_full |
The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans |
title_fullStr |
The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans |
title_full_unstemmed |
The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans |
title_sort |
fkbp5 gene affects alcohol drinking in knockout mice and is implicated in alcohol drinking in humans |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2016-08-01 |
description |
FKBP5 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. |
topic |
Fkbp5 knockout alcohol drinking behavior human alcohol use disorder |
url |
http://www.mdpi.com/1422-0067/17/8/1271 |
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