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. Author manuscript; available in PMC: 2023 May 1.
Published in final edited form as: Neurobiol Dis. 2022 Feb 7;166:105652. doi: 10.1016/j.nbd.2022.105652

Figure 7. Selective genetic inactivation of mHTT in the striatum results in a correlative reduction of CSF mHTT but not plasma mHTT.

Figure 7.

A) Graphical experimental overview where Hu97/18 and Hu97/18xS littermates were collected at 2, 6, and 10 months of age for quantification of mHTT in the CSF, plasma and brain by IP-FCM. B) Natural history of plasma mHTT with all values normalized to the mean mHTT MFI for 2 month old Hu97/18 mice (N=11–13 for Hu97/18, N=6–8 for Hu97/18xS per age. Two-way ANOVA: genotype p= 0.0613, age p= 0.5640, interaction p= 0.0152. Sidak’s multiple comparison test: Hu97/18 2 months vs 10 months *p= 0.0175; Hu97/18 vs Hu97/18xS at 2 months p= 0.4430, 6 months p= 0.0800, 10 months p= 0.0945; Test for linear trend: Hu97/18 *p= 0.0112, Hu97/18xS p=0.2068). C) Natural history of CSF mHTT with all values normalized to the mean mHTT MFI for 2 month old Hu97/18 mice (N=12–16 for Hu97/18, N=7–9 for Hu97/18xS per age. Two-way ANOVA: genotype p <0.0001, age p= 0.0078, interaction p=0.4469. Sidak’s multiple comparison test: Hu97/18 2 months vs 6 months: p= 0.4744, 2 months vs 10 months **p= 0.0026, 6 months vs 10 months *p= 0.0370; Hu97/18xS 2 months vs 6 months p= 0.9245, 2 months vs 10 months p= 0.5338, 6 months vs 10 months p= 0.2905; Hu97/18 vs Hu97/18xS at 2 months p= 0.2357, 6 months ##p= 0.0025, 10 months ##p= 0.0025; Test for linear trend: Hu97/18 **p=0.0057, Hu97/18xS **p=0.0049). D) Comparison of CSF and plasma mHTT levels shows a significant relationship in Hu97/18, but not Hu97/18xS mice (Linear regression: Hu97/18 R2= 0.1520, *p= 0.0188, Hu97/18xS R2= 0.0002, p= 0.9484). E) Comparison of plasma and brain mHTT IP-FCM MFI signal from Hu97/18 and Hu97/18xS mice at all ages does not show a relationship between plasma mHTT and STR or CTX mHTT (Linear regression: striatum R2= 0.0004, p= 0.9318; cortex R2= 0.0264, p= 0.5417). F) Comparison of CSF and brain mHTT mHTT IP-FCM MFI signal from Hu97/18 and Hu97/18xS mice at all ages demonstrates a significant correlation between CSF mHTT and striatal, but not cortical mHTT (Linear regression: STR R2= 0.5373, ****p= 0.0001; CTX R2= 0.07541, p= 0.2413). CTX = cortex, STR = striatum, CSF = cerebrospinal fluid, MFI = median fluorescence intensity.