ad mouse model 5 fad mice  (Jackson Laboratory)

Journal: The Journal of Clinical Investigation

Article Title: USP25 inhibition ameliorates Alzheimer’s pathology through the regulation of APP processing and A β generation

doi: 10.1172/JCI152170

Figure Lengend Snippet: ( A – C ) Representative immunostaining ( A ) and quantification of 6E10-positive amyloid plaques ( B and C ) in the hippocampi (Hipp) of 5-month-old 5×FAD ( n = 4) and 5×FAD;Dp16 ( n = 5) mice. Scale bar: 100 μm. ( D – F ) Representative immunostaining ( D ) and quantification of 6E10-positive amyloid plaques ( E and F ) in the hippocampi of 6-month-old 5×FAD ( n = 5) and 5×FAD;BAC-Tg-USP25 ( n = 6) mice. Scale bar: 100 μm. All data are presented as mean ± SEM. P values were determined by Student’s t test. * P < 0.05; ** P < 0.01; *** P < 0.001.

Article Snippet: Dp(16)1Yey/+ DS model mice ( , ) (referred to as Dp16 mice in this study; stock no. 013530) and 5×FAD AD model mice ( ) (stock no. 34840-JAX) were obtained from The Jackson Laboratory.

Techniques: Immunostaining

Journal: The Journal of Clinical Investigation

Article Title: USP25 inhibition ameliorates Alzheimer’s pathology through the regulation of APP processing and A β generation

doi: 10.1172/JCI152170

Figure Lengend Snippet: ( A ) Morris water maze (MWM) test results depicting escape latency, defined as the time taken to find a hidden platform in the 7-day training phase. ( B ) MWM probe test results. n = 13–19 mice per group. ( C ) Percentage freezing time in contextual fear conditioning (FC) tests as a readout of associative memory. n = 18 mice per group. Six- to 7-month-old mice were used in behavioral tests. ( D - I ) Representative immunostaining ( D ) and quantification of amyloid plaques with a 6E10 antibody ( E – G ) and thioflavin S (ThioS) ( H and I ) in the cortices (CTX) and hippocampi (Hipp) in 6-month-old 5×FAD and 5×FAD; Usp25 +/– mice. n = 6 mice per group. Scale bar: 50 μm. ( J and K ) Quantification of soluble Aβ 42 ( J ) and Aβ 40 ( K ) in RIPA buffer in the cortices and hippocampi of 6-month-old 5×FAD and 5×FAD; Usp25 +/– mice. n = 10 mice per group. ( L – N ) Golgi staining ( L ) and quantification of mature, immature, and total dendritic spines ( M ) and spine size ( N ) in the cortical layer V regions of 9-month-old WT, Usp25 +/– , 5×FAD, and 5×FAD; Usp25 +/– mice. Scale bar: 10 μm. n = 4 mice per group, 22–27 dendrites per group were counted in M , and 95–107 spines per group were counted in N . Data are presented as mean ± SEM ( A and E – K ) or as median with minimum to maximum bars ( B , C , M , and N ). P values were determined by 1-way ANOVA with Dunnett’s post hoc analysis in B and C , by the Mann-Whitney test in E – K , by 1-way ANOVA with Tukey’s post hoc analysis in M , and by Kruskal-Wallis test with Dunn’s post hoc analysis in N . * P < 0.05; ** P < 0.01; *** P < 0.001; # P < 0.0001.

Article Snippet: Dp(16)1Yey/+ DS model mice ( , ) (referred to as Dp16 mice in this study; stock no. 013530) and 5×FAD AD model mice ( ) (stock no. 34840-JAX) were obtained from The Jackson Laboratory.

Techniques: Immunostaining, Staining, MANN-WHITNEY

Journal: The Journal of Clinical Investigation

Article Title: USP25 inhibition ameliorates Alzheimer’s pathology through the regulation of APP processing and A β generation

doi: 10.1172/JCI152170

Figure Lengend Snippet: ( A and B ) Immunoblot analysis of APP-processing-related proteins in the cortices of 6-month-old WT, Usp25 +/– , 5×FAD, and 5×FAD: Usp25 +/– mice. n = 5 per group. ( C and D ) Immunoblot analysis of APP, BACE1, and USP25 proteins in the cortices of 6-month-old WT and BAC-Tg-USP25 mice. n = 8 per group. The intensity of each immunoblot band was normalized to that of the β-actin band. All data are presented as median with minimum to maximum bars. Values are shown in kDa in A and C . P values were determined by ordinary 1-way ANOVA with Tukey’s post hoc analysis in B and by Student’s t test in D . * P < 0.05; *** P < 0.001; **** P < 0.0001.

Article Snippet: Dp(16)1Yey/+ DS model mice ( , ) (referred to as Dp16 mice in this study; stock no. 013530) and 5×FAD AD model mice ( ) (stock no. 34840-JAX) were obtained from The Jackson Laboratory.

Techniques: Western Blot

Journal: The Journal of Clinical Investigation

Article Title: USP25 inhibition ameliorates Alzheimer’s pathology through the regulation of APP processing and A β generation

doi: 10.1172/JCI152170

Figure Lengend Snippet: ( A ) Seven-month-old 5×FAD mice were intraperitoneally injected with vehicle or AZ1 (20 mg/kg/d) for 4 weeks and then subjected to pathological analyses. ( B ) Representative immunostaining of 6E10-positive amyloid plaques in 5×FAD+vehicle (Veh) and 5×FAD+AZ1 mice. Scale bar: 500 μm (merge); 250 μm (zoom in (high-magnification images to the right and below merge images)). ( C–F ) Quantification of 6E10-positive amyloid plaques in the mouse cortex (CTX) ( C and D ) and hippocampus (Hipp) ( E and F ). n = 5 mice per group. ( G ) Representative immunostaining of 6E10-positive amyloid plaques and LAMP1-positive dystrophic neurites in the hippocampi of 5×FAD+vehicle and 5×FAD+AZ1 mice. Scale bar: 100 μm (merge); 20 μm (Zoom in). ( H ) Quantification of LAMP1-positive dystrophic neurites in G . n = 5 mice per group. ( I ) Quantification of amyloid plaque–associated LAMP1-positive dystrophic neurites in G . n = 5 mice and 55 amyloid plaques (5×FAD+Veh), n = 5 mice and 47 amyloid plaques (5×FAD+AZ1). Data are presented as mean ± SEM ( C – F and H ) or median with minimum to maximum bars ( I ). P values were determined by Student’s t test in C – F and by the Mann-Whitney test in H , I , K , and L . * P < 0.05; ** P < 0.01.

Article Snippet: Dp(16)1Yey/+ DS model mice ( , ) (referred to as Dp16 mice in this study; stock no. 013530) and 5×FAD AD model mice ( ) (stock no. 34840-JAX) were obtained from The Jackson Laboratory.

Techniques: Injection, Immunostaining, MANN-WHITNEY