Fig. 1: PGRN loss does not exacerbate TDP-43 pathology in TDP-43Q331K/Q331K mice.
From: Progranulin deficiency does not exacerbate TDP-43 pathology in TDP-43 transgenic mouse models
A Immunostaining of TDP-43 and NeuN in brain sections from 16-month-old mice WT, TDP-43Q331K/Q331K (Q331K), Grn−/−, TDP-43Q331K/Q331K Grn−/− (Q331K Grn−/−) mice. Representative images from the cortex were shown. Scale bar, 10 µm. B Analysis of TDP-43, phosphorylated TDP-43 (pS409/410), and PGRN levels in cortical lysates from 16-month-old mice of the indicated genotypes. C TDP-43 levels in RIPA- and urea-soluble fractions were quantified. Data are presented as mean ± SEM from 3 mice per group (n = 3). One-way ANOVA tests with Bonferroni’s multiple comparisons. D PGRN levels in RIPA soluble fractions were quantified and normalized to GAPDH. Data are presented as mean ± SEM from 3 mice per group (n = 3). E Total RNAs were extracted from the cortex of 10-month-old WT, TDP-43Q331K/Q331K, Grn−/−, TDP-43Q331K/Q331KGrn−/− male mice, and the RT-qPCR was performed to analyze the splicing changes in Sort1 exon 17b (left) and Mapt exons 2 and 3 (right). The relative mRNA levels of transcripts including or excluding exons 2 and 3 represent the inclusion of Mapt exons 2 and 3. Data are presented as mean ± SEM (n = 4 mice per genotype). p-values were determined using one-way ANOVA tests with Bonferroni’s multiple comparisons. F Expression levels of Tardbp in WT and Q331K mice. Total RNAs were extracted from the cortex of 10-month-old WT and Q331K male mice, and the RNA-seq was performed to analyze gene expression changes. Normalized read counts are shown. Data are presented as mean ± SEM (n = 5-6 mice per genotype). *p < 0.05, unpaired two-tailed Student's t-test.
