B6J.129X1(Cg)-Fkbp5^tm1Dvds/CiofJ

Stock number: 035160
Product name: FKBP51 knock-out (Fkbp5-lacZ KO)
Research areas: Cell Biology Research, Neurobiology Research, Research Tools

Description

The Fkbp5 (FKBP51) gene is disrupted by lacZ in this knock-out allele. Aged mice exhibit anti-depressive behavior in behavioral tests, reduced stress corticosterone levels and may be useful for studying anxiety and depressive disorders, as well as endothelial barrier integrity.

Detailed description

FKBP5 (or FKBP51) functions as a co-chaperone that binds to HSP90 and is involved in regulation of the glucocorticoid receptor. Mutations that increase protein levels of human FKBP5 are associated with depressive disorders, anxiety, bipolar disorders, and post-traumatic stress syndrome. In this strain, the targeting vector includes a lacZ gene and replaces the Fkbp5 first coding exon. Expression of beta-galactosidase is under the control of the endogenous promoter. Expression in the brain increases with age particularly in the upper cortical layers of the forebrain. Homozygous mice are viable and fertile. Aged mice (over a year old) exhibit shorter immobility time in forced swim and tail suspension tests, and reduced stress corticosterone levels. This strain may be useful for studying anxiety and depressive disorders.

Fkbp5 knock-out mice have also been used to demonstrate that FKBP51 is a novel regulator of endothelial barrier integrity. This finding is significant as it reveals a protective mechanism for endothelium against calcium entry-induced disruption.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing the lacZ gene and a PGKneo cassette was used to replace exon 2, the first coding exon. Expression of beta-galactosidase is under the control of the endogenous promoter and is expressed in frame with the initiation codon. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred C57BL/6 mice. The strain was maintained at the Mayo Clinic and then transferred to the laboratory of Dr. Chad Dickey at the University of South Florida. The Fkbp5 allele was maintained on a mixed Swiss-Webster and C57BL/6 background for many generations and sent to The Jackson Laboratory for preservation and distribution (see Stock No. 017989). Mixed background mice were acquired from The Jackson Laboratory by Dr. Donna Cioffi of the University of Southern Alabama and backcrossed to C57BL/6J (Stock No. 000664) for 10 generations to create this line (Stock No. 035160).

Allele

Symbol: Fkbp5^tm1Dvds
Name: targeted mutation 1, David F Smith
MGI accession ID: MGI:5296970
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: 51KO; Fkbp51^-
Marker symbol: Fkbp5
Marker name: FK506 binding protein 5
Marker synonyms: AIG6; D17Ertd592e; Dit1; FKBP-5; FKBP51; FKBP-51; FKBP54; P54; PPIase; Ptg-10
Chromosome: 17
Strain of origin: 129X1/SvJ
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: lacZ is expressed in areas of the brain.
Molecular note: Exon 2 was replaced with a lacZ and neo cassette. The absence of protein expression was confirmed by western blot analysis on brain extracts.