fkbp5 knockout mice  (Shanghai Model Organisms Center)

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: Attenuation of OGD-induced aberrant synaptic plasticity in FKBP5 KO mice. A Representative traces and time course of fEPSP slope recorded in the hippocampus during baseline, OGD induction, and iLTP expression over a 60-minute period B Summary of mean fEPSP slopes during the 5-minute OGD induction phase in WT and FKBP5 KO mice (WT, n = 4 slices from 3 mice; FKBP5 KO, n = 9 slices from 5 mice). Data are presented as mean ± SEM; Student’s t-test. C Summary of mean fEPSP slopes during the iLTP expression phase (last 10 min of recording) in WT and FKBP5 KO mice (WT, n = 4 slices from 3 mice; FKBP5 KO, n = 9 slices from 5 mice). Data are presented as mean ± SEM; *** p < 0.001 compared with the WT group; Student’s t-test. D Representative Western blots showing protein levels of GluN2B and FKBP51 in the hippocampus of control and OGD-treated groups. E Quantification of GluN2B expression levels ( n = 10). Data are presented as mean ± SEM; *** p < 0.001 compared with the control group; Student’s t-test. F Quantification of FKBP51 expression levels, analyzed using ImageJ and normalized to the control group ( n = 10). Data are presented as mean ± SEM; *** p < 0.001 compared with the control group; Student’s t-test

Article Snippet: Homozygous Fkbp5 knockout mice ( Fkbp5 tm1Dvds , JAX stock #017989) were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) and maintained on a C57BL/6J background.

Techniques: Expressing, Western Blot, Control

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: FKBP5 inhibitor SaFit2 prevents OGD-induced aberrant synaptic plasticity. A Representative traces and the Input-output (I–O) curve in control and 0.5 µM SaFit2 groups ( n = 6 slices from 3 mice). Data are presented as mean ± SEM; Student’s t-test. B Paired-pulse ratio (PPR) evoked at a function of intervals of 30 to 360 ms in control and 0.5 µM SaFit2 groups ( n = 7 slices from 5 mice). Data are presented as mean ± SEM; Student’s t-test. C Representative traces and time course of fEPSP slope recorded in the hippocampus during baseline and OGD induction over a 75-minute period. D Summary of mean fEPSP slopes during the 5-minute OGD induction phase in basal and OGD + 0.5 µM SaFit2 pretreatment groups ( n = 9 slices from 4 mice). Data are presented as mean ± SEM; Student’s t-test. E Representative traces and time course of fEPSP slope recorded during baseline, OGD induction, and OGD + 0.5 µM SaFit2 administration. F Summary of mean fEPSP slopes during the 5-minute OGD induction phase in basal, OGD, and OGD + 0.5 µM SaFit2 groups ( n = 3 slices from 3 mice). Data are presented as mean ± SEM; * p < 0.05 compared with basal, # p < 0.05 compared with OGD; one-way ANOVA with Bonferroni post hoc test

Article Snippet: Homozygous Fkbp5 knockout mice ( Fkbp5 tm1Dvds , JAX stock #017989) were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) and maintained on a C57BL/6J background.

Techniques: Control

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: Differential modulation of synaptic responses and GluN2B/FKBP51 expression by anodal and cathodal DCS. A Representative traces and average time course of fEPSP slope recorded in the hippocampus during a 75-minute period with anodal or cathodal DCS intervention. B Summary of mean fEPSP slopes at baseline and during DCS intervention in the anodal DCS group. n = 4 slices from 3 mice. Data are presented as mean ± SEM in each experiment. * p < 0.05 compared with basal; Student’s t-test. C Summary of mean fEPSP slopes at baseline and during DCS intervention in the cathodal DCS group. n = 5 slices from 3 mice. Data are presented as mean ± SEM in each experiment. *** p < 0.001 compared with basal; Student’s t-test

Article Snippet: Homozygous Fkbp5 knockout mice ( Fkbp5 tm1Dvds , JAX stock #017989) were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) and maintained on a C57BL/6J background.

Techniques: Expressing

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: Cathodal DCS reverses OGD-induced iLTP and downregulates GluN2B and FKBP51 expression. A Average time course of fEPSP slope recorded in the hippocampus during a 135-minute period covering baseline, OGD induction, and cathodal DCS intervention. B Summary of mean fEPSP slopes at baseline, during OGD induction, and cathodal DCS intervention. n = 5 slices from 5 mice. Data are presented as mean ± SEM in each experiment. *** p < 0.001 compared with basal, ### p < 0.001 compared with OGD; one-way ANOVA with Bonferroni post-hoc . C Representative Western blots showing protein levels of GluN2B and FKBP51 in the control, control + cathodal DCS, OGD, and OGD + cathodal DCS groups. D Quantification of GluN2B expression levels. n = 6 in each group. Data are presented as mean ± SEM in each experiment. * p < 0.05 compared with basal, ## p < 0.01 compared with OGD; one-way ANOVA with Bonferroni post-hoc . E Quantification of FKBP51 expression levels. n = 6 in each group. Data are presented as mean ± SEM; * p < 0.05 compared with indicated control, ### p < 0.001 compared with OGD group; one-way ANOVA with Bonferroni post-hoc

Article Snippet: Homozygous Fkbp5 knockout mice ( Fkbp5 tm1Dvds , JAX stock #017989) were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) and maintained on a C57BL/6J background.

Techniques: Expressing, Western Blot, Control

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: GluN2B-mediated ischemic LTP is underpinned by FKBP51, which can be inhibited by cathodal DCS. This schematic diagram illustrates the crucial role of FKBP51 in ischemic LTP and highlights the potential of cathodal DCS to target this pathological form of synaptic plasticity. Following OGD induction, ischemic LTP was observed, accompanied by elevated expression of the NMDAR subunit GluN2B and FKBP51. The OGD-induced potentiation and GluN2B upregulation were prevented by genetic deletion of Fkbp 5 or by pharmacological inhibition of FKBP51 (SAFit2), thereby implicating Fkbp5 /FKBP51 in this maladaptive plasticity. Moreover, cDCS reversed iLTP and reduced GluN2B and FKBP51 expression, indicating that both the ischemic LTP and FKBP51 upregulation are suppressible by cDCS in this GluN2B-dependent pathway

Article Snippet: Homozygous Fkbp5 knockout mice ( Fkbp5 tm1Dvds , JAX stock #017989) were obtained from The Jackson Laboratory (Bar Harbor, ME, USA) and maintained on a C57BL/6J background.

Techniques: Expressing, Inhibition

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: Attenuation of OGD-induced aberrant synaptic plasticity in FKBP5 KO mice. A Representative traces and time course of fEPSP slope recorded in the hippocampus during baseline, OGD induction, and iLTP expression over a 60-minute period B Summary of mean fEPSP slopes during the 5-minute OGD induction phase in WT and FKBP5 KO mice (WT, n = 4 slices from 3 mice; FKBP5 KO, n = 9 slices from 5 mice). Data are presented as mean ± SEM; Student’s t-test. C Summary of mean fEPSP slopes during the iLTP expression phase (last 10 min of recording) in WT and FKBP5 KO mice (WT, n = 4 slices from 3 mice; FKBP5 KO, n = 9 slices from 5 mice). Data are presented as mean ± SEM; *** p < 0.001 compared with the WT group; Student’s t-test. D Representative Western blots showing protein levels of GluN2B and FKBP51 in the hippocampus of control and OGD-treated groups. E Quantification of GluN2B expression levels ( n = 10). Data are presented as mean ± SEM; *** p < 0.001 compared with the control group; Student’s t-test. F Quantification of FKBP51 expression levels, analyzed using ImageJ and normalized to the control group ( n = 10). Data are presented as mean ± SEM; *** p < 0.001 compared with the control group; Student’s t-test

Article Snippet: There is no report about abnormal developmental consequences in Fkbp5 knockout mice on The Jackson Laboratory.

Techniques: Expressing, Western Blot, Control

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: FKBP5 inhibitor SaFit2 prevents OGD-induced aberrant synaptic plasticity. A Representative traces and the Input-output (I–O) curve in control and 0.5 µM SaFit2 groups ( n = 6 slices from 3 mice). Data are presented as mean ± SEM; Student’s t-test. B Paired-pulse ratio (PPR) evoked at a function of intervals of 30 to 360 ms in control and 0.5 µM SaFit2 groups ( n = 7 slices from 5 mice). Data are presented as mean ± SEM; Student’s t-test. C Representative traces and time course of fEPSP slope recorded in the hippocampus during baseline and OGD induction over a 75-minute period. D Summary of mean fEPSP slopes during the 5-minute OGD induction phase in basal and OGD + 0.5 µM SaFit2 pretreatment groups ( n = 9 slices from 4 mice). Data are presented as mean ± SEM; Student’s t-test. E Representative traces and time course of fEPSP slope recorded during baseline, OGD induction, and OGD + 0.5 µM SaFit2 administration. F Summary of mean fEPSP slopes during the 5-minute OGD induction phase in basal, OGD, and OGD + 0.5 µM SaFit2 groups ( n = 3 slices from 3 mice). Data are presented as mean ± SEM; * p < 0.05 compared with basal, # p < 0.05 compared with OGD; one-way ANOVA with Bonferroni post hoc test

Article Snippet: There is no report about abnormal developmental consequences in Fkbp5 knockout mice on The Jackson Laboratory.

Techniques: Control

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: Differential modulation of synaptic responses and GluN2B/FKBP51 expression by anodal and cathodal DCS. A Representative traces and average time course of fEPSP slope recorded in the hippocampus during a 75-minute period with anodal or cathodal DCS intervention. B Summary of mean fEPSP slopes at baseline and during DCS intervention in the anodal DCS group. n = 4 slices from 3 mice. Data are presented as mean ± SEM in each experiment. * p < 0.05 compared with basal; Student’s t-test. C Summary of mean fEPSP slopes at baseline and during DCS intervention in the cathodal DCS group. n = 5 slices from 3 mice. Data are presented as mean ± SEM in each experiment. *** p < 0.001 compared with basal; Student’s t-test

Article Snippet: There is no report about abnormal developmental consequences in Fkbp5 knockout mice on The Jackson Laboratory.

Techniques: Expressing

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: Cathodal DCS reverses OGD-induced iLTP and downregulates GluN2B and FKBP51 expression. A Average time course of fEPSP slope recorded in the hippocampus during a 135-minute period covering baseline, OGD induction, and cathodal DCS intervention. B Summary of mean fEPSP slopes at baseline, during OGD induction, and cathodal DCS intervention. n = 5 slices from 5 mice. Data are presented as mean ± SEM in each experiment. *** p < 0.001 compared with basal, ### p < 0.001 compared with OGD; one-way ANOVA with Bonferroni post-hoc . C Representative Western blots showing protein levels of GluN2B and FKBP51 in the control, control + cathodal DCS, OGD, and OGD + cathodal DCS groups. D Quantification of GluN2B expression levels. n = 6 in each group. Data are presented as mean ± SEM in each experiment. * p < 0.05 compared with basal, ## p < 0.01 compared with OGD; one-way ANOVA with Bonferroni post-hoc . E Quantification of FKBP51 expression levels. n = 6 in each group. Data are presented as mean ± SEM; * p < 0.05 compared with indicated control, ### p < 0.001 compared with OGD group; one-way ANOVA with Bonferroni post-hoc

Article Snippet: There is no report about abnormal developmental consequences in Fkbp5 knockout mice on The Jackson Laboratory.

Techniques: Expressing, Western Blot, Control

Journal: Neurochemical Research

Article Title: Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation

doi: 10.1007/s11064-025-04578-6

Figure Lengend Snippet: GluN2B-mediated ischemic LTP is underpinned by FKBP51, which can be inhibited by cathodal DCS. This schematic diagram illustrates the crucial role of FKBP51 in ischemic LTP and highlights the potential of cathodal DCS to target this pathological form of synaptic plasticity. Following OGD induction, ischemic LTP was observed, accompanied by elevated expression of the NMDAR subunit GluN2B and FKBP51. The OGD-induced potentiation and GluN2B upregulation were prevented by genetic deletion of Fkbp 5 or by pharmacological inhibition of FKBP51 (SAFit2), thereby implicating Fkbp5 /FKBP51 in this maladaptive plasticity. Moreover, cDCS reversed iLTP and reduced GluN2B and FKBP51 expression, indicating that both the ischemic LTP and FKBP51 upregulation are suppressible by cDCS in this GluN2B-dependent pathway

Article Snippet: There is no report about abnormal developmental consequences in Fkbp5 knockout mice on The Jackson Laboratory.

Techniques: Expressing, Inhibition

Journal: Cell Death & Disease

Article Title: FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment

doi: 10.1038/s41419-023-06260-7

Figure Lengend Snippet: A The degree of myelin loss in Fkbp5 ko mice were significantly lower than that in WT under the same conditions of CPZ induction model building flow chart. B RT-PCR examination of Fkbp5 expression levels in WT and Fkbp5 ko mice ( n = 3, t -test). C Results of LFB staining and MBP fluorescence staining of brain tissue sections from blank-treated mice of WT or Fkbp5 ko and their corresponding CPZ model building mice. LFB staining and MBP fluorescence staining results analyzed by the Image J software for gray value of the white dotted box area. LFB staining and MBP fluorescence staining results for sections with a thickness of 20 μm, scale bars = 500 μm. D Behavioral statistics of rod turning experiments in mice with a fully automated rod turning machine speed of 30 rpm, each observation time of 3 min, and three observations per mouse for averaging ( n = 11, two-way). E , F Separate staining for the two stains in C . IOD statistics were performed ( n = 6, two-way).

Article Snippet: FKBP5 knockout C57BL/6 N mice (Fkbp5 ko ), No. EGE-ZQ-047 was provided by the Biocytogen Co., Ltd. (Beijing, China).

Techniques: Reverse Transcription Polymerase Chain Reaction, Expressing, Staining, Fluorescence, Software

Journal: Cell Death & Disease

Article Title: FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment

doi: 10.1038/s41419-023-06260-7

Figure Lengend Snippet: A Fluorescence staining maps showing changes in microglia (red) and astrocytes (green) in the corpus callosum and surrounding tissue regions of brain tissue in WT and Fkbp5 ko mice at 0, 1, and 3 weeks after induction of demyelination. Two regions were identified as glial cell enrichment areas by low magnification observations. The lateral horn of the ventricle is located in the region of the corpus callosum (shown by the dashed box) and the central region of the coronal section of the corpus callosum (dashed oval box), and both are framed in the region of the corpus callosum at high magnification. B , C , E , F Histograms of the number of positive microglia and astrocytes at the two locations, with the two arms in the downward column and the central location in the upward column. D , G Equal masses of fresh tissues from each group were cut up, treated with trypsin, and then detected at two wavelengths of 420 and 600 nm for superoxide anion (O 2 ▪- ) content and counted, respectively.

Article Snippet: FKBP5 knockout C57BL/6 N mice (Fkbp5 ko ), No. EGE-ZQ-047 was provided by the Biocytogen Co., Ltd. (Beijing, China).

Techniques: Fluorescence, Staining

Journal: Cell Death & Disease

Article Title: FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment

doi: 10.1038/s41419-023-06260-7

Figure Lengend Snippet: A GO pathway enrichment analysis, including multiple pathways of cellular autophagy, mitophagy and cellular metabolism. B Volcano plot showing the changes in gene expression in the WT mice vs. Fkbp5 ko mice. Green represents downregulation, and red represents upregulation. C PPI analysis of the FKBP51 interactions with mitophagy-associated proteins. D Heatmap analysis of differentially expressed genes associated with mitophagy between groups, with stronger color biases toward blue indicating lower expressions and stronger biases toward red indicating higher expressions. Membrane-making had the opposite trend of Fkbp5 expressions to that of Pparg and Bcl2, and the same as Pink1. E Bubble plots of the KEGG enrichment analysis in the WT mice blank vs. model group. Bubble sizes represent the numbers of enriched genes, where Fkbp5 was enriched in the estrogen signaling pathway and Pparg was enriched in the longevity regulating pathway (marked by red box), p < 0.05. F , G Showing RT-PCR results of Fkbp5 and Bcl2 interference by siRNA in primary brain tissue cultures, respectively ( n = 3, one-way). H Flow cytometry in the FITC green fluorescence band validated the results of ROS production in different subgroups, showing a relative role for Fkbp5 versus Bcl2. I MMP under starvation (EBSS treatment for 1.5 h) conditions by JC-1, showing a significant decrease in MMP in the Bcl2-interfered group, while the Fkbp5-interfered group improved relative to the CON+EBSS group.

Article Snippet: FKBP5 knockout C57BL/6 N mice (Fkbp5 ko ), No. EGE-ZQ-047 was provided by the Biocytogen Co., Ltd. (Beijing, China).

Techniques: Expressing, Membrane, Reverse Transcription Polymerase Chain Reaction, Flow Cytometry, Fluorescence

Journal: Cell Death & Disease

Article Title: FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment

doi: 10.1038/s41419-023-06260-7

Figure Lengend Snippet: A , B The results of RT-PCR tests on RNA extracted after incubation for more over 48 h in four groups corresponding to the subsequent experimental base groupings of blank treatment, interference with Fkbp5, interference with Pparg, and simultaneous LV infection overexpressing Fkbp5 and interference with statistical plots ( n = 3, one-way). C – E Staining results of active mitochondria and ROS, with ROS fluorescently labeled in green and active mitochondria fluorescently labeled in red, in nine groups in a mouse-derived microglial cell line (BV2) based on interference with FKBP5 and PPAR-γ; overexpression of FKBP5 and interference with PPAR-γ were observed on the basis of these two genes on cells in LPS after 6 h of induction, and Rosup (a class of drugs that stimulate the production of ROS) was designed to treat the stimulated cells as a positive control, which is located in the upper left corner of the CON group. Fluorescence readings of ROS and active mitochondria were collected and statistically analyzed between groups using a fluorescent zymograph in the 488–525 nm and 579–599 nm bands, respectively ( n = 14, one way). F The oxygen content of each subgroup of primary brain tissue cultures in the last 200 min was recorded after 24 h of treatment with 3 mM CPZ as verified by the Oxygen Probe fluorescence reaction, with a test interval of 10 min and a detection band at 500–650 nm ( n = 3). G Verification of Pparg expression levels under CPZ induction by RT-PCR in primary brain tissue cultures ( n = 3, two-way). H Calculation of OCR per unit time for each group based on Figure F data ( n = 3, t -test). I Luminescent ATP kit to detect ATP production after 4 h of CPZ treatment in each primary brain tissue culture group ( n = 3, two-way).

Article Snippet: FKBP5 knockout C57BL/6 N mice (Fkbp5 ko ), No. EGE-ZQ-047 was provided by the Biocytogen Co., Ltd. (Beijing, China).

Techniques: Reverse Transcription Polymerase Chain Reaction, Incubation, Infection, Staining, Labeling, Derivative Assay, Over Expression, Positive Control, Fluorescence, Expressing

Journal: Cell Death & Disease

Article Title: FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment

doi: 10.1038/s41419-023-06260-7

Figure Lengend Snippet: A Visualization of the rigid molecular simulations of docking between FKBP51 and PPAR-γ. free energy is below zero, so spontaneous docking is considered. B CoIP results pulled with mouse-derived FKBP51 antibody indicate an interaction between the two proteins. “input” results indicate non-IP WB bands, both proteins are detectable, and negative control results “N” signal. C Protein blots showing FKBP51 and PPAR-γ results, with GAPDH selected as the internal reference protein. D Microscopic cell maps taken using confocal for each genotype and its model group, box marks indicate overlapping regions of proteins and co-localization results (WT, CPZ, Fkbp5 ko , Pearson’ coefficient R values and Manders’ coefficients for CPZ-Fkbp5 ko were 0.49 and 0.878; 0.85 and 0.978; 0.58 and 0.929; 0.86 and 0.960, respectively). E – H shows WB and RT-PCR statistics for the two classes of proteins, respectively, with no differences between labeled groups indicating no statistical differences ( n = 6, one-way). I Results of immunofluorescence of two types of proteins, green fluorescence points to FKBP51 and red to PPAR-γ, showing the results of co-staining immunofluorescence of two types of proteins.

Article Snippet: FKBP5 knockout C57BL/6 N mice (Fkbp5 ko ), No. EGE-ZQ-047 was provided by the Biocytogen Co., Ltd. (Beijing, China).

Techniques: Derivative Assay, Negative Control, Reverse Transcription Polymerase Chain Reaction, Labeling, Immunofluorescence, Fluorescence, Staining

Journal: Cell Death & Disease

Article Title: FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment

doi: 10.1038/s41419-023-06260-7

Figure Lengend Snippet: A Visualization part of the rigid molecular simulation of docking between FKBP51 and PPAR-γ, with a free energy level of −3.3 to −3.5 kcal/mol, spontaneous docking is considered possible. B Fluorescence results of PPAR-γ co-staining with PINK1, scale bars = 50 μm, obtained by confocal microscopy and statistics from boxed area colocalization analysis, scale bars = 5 μm, are shown separately. C The results of docking with mouse-derived FKBP51 antibody and CoIP results obtained with rabbit-derived PPAR-γ antibody, indicating an interaction among these three proteins. The input results indicate non-IP WB bands, both proteins are detectable and negative control results (N) with weak or no signal, and a weaker signal for PINK1 was obtained with the FKBP51 antibody.

Article Snippet: FKBP5 knockout C57BL/6 N mice (Fkbp5 ko ), No. EGE-ZQ-047 was provided by the Biocytogen Co., Ltd. (Beijing, China).

Techniques: Fluorescence, Staining, Confocal Microscopy, Derivative Assay, Negative Control