Fig 1: Genetic reduction of progranulin expression reduces macroorchidism in Fmr1 KO mice without modifying FXS-associated behavioural phenotypes. Body weight (A), behaviour (B–D) and testes weight (E) are characterized in n = 23 wild type (Fmr1+; Grn+/+), n = 20 Fmr1+; Grn+/-, n = 17 Fmr1 KO; Grn+/+, and n = 15 Fmr1 KO; Grn+/- male mice, aged 2–3 months. Activity in open field is measured in (B), while the results of the elevated plus maze and marble burying are shown in (C) and (D) respectively. Testes weight (E) is given as the combined weight of both testes from a single individual. Data are presented as mean ± standard error of the mean (SEM). Data are analyzed by two-way ANOVA for Fmr1 and Grn gene dosage. Šídák's multiple comparisons test was conducted between the Fmr1 KO; Grn+/+ and Fmr1 KO; Grn+/- genotypes to assess whether progranulin reduction could modify FXS-associated phenotypes on an Fmr1 KO background. *p < 0.05 by two-way ANOVA, ****p < 0.0001 by two-way ANOVA, ns not significant.
Fig 2: Loss of Fmr1 expression in mice does not modify cortical ERK, pERK, or MMP9 expression. Cortical ERK expression is evaluated by western blot in n = 8 wild-type (Fmr1+; Grn+/+; black circles) and n = 8 Fmr1 KO (Fmr1 KO; Grn+/+; teal triangles) male mice at 3 months of age (A,B). Similarly, pERK expression and the pERK/ERK ratio are evaluated in the same samples in (C,D) and (E), respectively. MMP9 expression is shown in (F,G). ERK and pERK are normalized to calnexin, while MMP9 expression is normalized to β-tubulin. Cortical lysate input is normalized to 30ug total protein by Bradford assay. Data are presented as mean ± standard error of the mean (SEM). Data are analyzed by unpaired t-test. No significant difference is observed in any comparison.
Fig 3: Genetic reduction of progranulin expression does not modify cortical ERK, pERK, or MMP9 expression on an Fmr1 KO background. Cortical ERK expression is evaluated by western blot in n = 8 Fmr1 KO; Grn+/+ (teal triangles) and n = 8 Fmr1 KO; Grn+/- (dark blue inverted triangles) male mice at 3 months of age (A,B). Similarly, pERK expression and the pERK/ERK ratio are evaluated in the same samples in (C,D) and (E), respectively. MMP9 expression is shown in (F,G). ERK and pERK are normalized to calnexin, while MMP9 expression is normalized to β-tubulin. Cortical lysate input is normalized to 30ug total protein by Bradford assay. Data are presented as mean ± standard error of the mean (SEM). Data are analyzed by unpaired t-test. No significant difference is observed in any comparison. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
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