Journal: bioRxiv
Article Title: Rescue of FTLD-associated TDP-43 pathology and neurodegeneration by peripheral AAV-mediated expression of brain-penetrant progranulin
doi: 10.1101/2023.07.14.549089
Figure Lengend Snippet: ( A ) UMAP depiction of full transcript profile comparing untreated and AAV(L):bPGRN-treated WT and DKO mice (n=7/group). ( B ) Heatmap showing the top 222 differentially expressed genes in DKO mice and correction with AAV(L):bPGRN with a false discovery rate (FDR) < 5% and at least a 20% change comparing WT and DKO as well as DKO AAV and DKO. Plotted values are log2 transformed fold changes (FC) (n=7/group). ( C ) Transcriptional changes in genes linked to lysosomal function (n=7/group). ( D ) Representative immunofluorescence images of the thalamus of WT and DKO mice after treatment showing Iba1 + , Gfap + and Cd68 + cells (scalebar = 10 µm). ( E ) Quantification of the Gfap + , Iba1 + and Iba + /Cd68 + area in whole brain hemispheres (n=3/group). ( F ) mTrem2 levels in plasma (left, n=7/group), brain (middle, n=5-7/group) and liver (right, n=3/group) of WT and DKO mice after treatment at the end of the study as assessed by ELISA. C, E, F: Data is depicted as mean ± SD, data points represent individual animals. For statistical analysis, one-way ANOVA with Tukey’s multiple comparison was performed. ns p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
Article Snippet: Human PGRN levels in Grn KO mice were measured using the DuoSet ELISA kit (R&D DY2420) as previously described ( ).
Techniques: Transformation Assay, Immunofluorescence, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, Comparison