Fig. 1: Deletion of Alk5 gene in adult microglia results in microglial dyshomeostasis and microgliosis but not astrogliosis in the adult mouse brain. | Nature Communications

Fig. 1: Deletion of Alk5 gene in adult microglia results in microglial dyshomeostasis and microgliosis but not astrogliosis in the adult mouse brain.

From: Inhibition of TGF-β signaling in microglia stimulates hippocampal adult neurogenesis and reduces anxiety-like behavior in adult mice

Fig. 1: Deletion of Alk5 gene in adult microglia results in microglial dyshomeostasis and microgliosis but not astrogliosis in the adult mouse brain.

A A mouse model and experimental timeline for targeting microglial Alk5 and analyzing microglia homeostatic marker expression and microgliosis 3 weeks post tamoxifen. B, C Representative images of the hippocampus stained for IBA1, TMEM119, P2RY12 (BioLegend Ab), and GFAP in B Cx3cr1CreER-ALK5wt/wt or C Cx3cr1CreER-ALK5fl/fl mice D FACS-sorted GFP+ microglia were analyzed for mRNA levels using qRT-PCR showing E Alk5 (indicating gene deletion efficiency), F Tmem119, G P2ry12, H Tnf, and I Igf1 expression levels in control and iKO microglia (EI) (n = 3 for control, n = 3 for Alk5 KO, * p = 0.0146 for panel E, *** p = 0.0005 for panel F, *** p = 0.0004 for panel G, * p = 0.0372 for panel H, * p = 0.0167 for panel I, two-sided student’s t-test was used for statistical analysis for panels E-I). Representative immunohistochemistry images of IBA1, Ki67, and DAPI in the cortex of J Cx3cr1CreER-ALK5wt/wt or K Cx3cr1CreER-ALK5fl/fl at 3 weeks after TAM treatment. Arrows show Ki67+ cells (yellow arrows show Ki67+ cells not co-localized with IBA1+ cells and white arrows show Ki67+ cells co-localizing with IBA1+ cells). Unbiased stereological quantification for L Microglia density, M Astrocyte density, N total number of Ki67+ cells, and O the number of IBA1 + /Ki67+ cells (LO) (n = 4 for control, n = 3 for Alk5 KO, ** p = 0.002, *** p < 0.001, and ** p = 0.001 for panel L, ns = not significant for panel M, ** p < 0.001, p < 0.00, and p = 0.011 for panel N, ** p < 0.001, *** p < 0.001, and ** p = 0.006 for panel O, two-sided 2-way ANOVA with Tukey post hoc pairwise comparison was used for statistical analysis for panels LO). Each data point represents the average of a single animal ( > 3 brain sections per mouse for each brain region). The sex of each animal is represented by open circles (females) and open triangles (males). Mean ± SE. Scale bar as indicated. Panel A was created in BioRender. Luo, A. (2026) https://BioRender.com/0xildk2. Source data are provided as a source data file.

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