Extended Data Fig. 2: Inducible deletion of Bcl6 in adult mice results in muscle loss.
From: Transcriptional programming of translation by BCL6 controls skeletal muscle proteostasis
(a, b) Serial measurements of total body, lean, and fat mass in (a) n = 6 Cre+oil, n = 9 Cre-tmx and n = 9 Bcl6i-MKO male and (b) n = 6 Cre+oil, n = 8 Cre-tmx and n = 8 Bcl6i-MKO female mice starting at 8 weeks of age prior to (pre) and up to 12 weeks after treatment. Two-way ANOVA with Tukey’s multiple comparisons test was performed. (c, d) Weights of quadriceps (quad), gastrocnemius (gastroc), tibialis anterior (TA), extensor digitorum longus (EDL) and soleus from Cre+oil, Cre-tmx and Bcl6i-MKO (c) male and (d) female mice 12 weeks after treatment (n = same as (a,b)). One-way ANOVA with Dunnett’s multiple comparisons test was performed. (e) Tissue weights in n = 4 ad lib chow fed and n = 5 48-hour fasted C57BL/6 male mice. (f) qPCR of Bcl6 normalized to 36b4 in muscles from fed and 48-hour fasted mice (n = 3/group). (g) Western blot and densitometry of BCL6 and Actin in n = 4 fed and n = 5 from 48 hour fasted mouse quadriceps. Unpaired, two-tailed t-test with Welch correction was performed in (e-g). (h) Bcl6 levels in published cancer-associated cachexia syndrome (CACS) models. GEO accession numbers are listed. Control vs C26 colon cancer P = 0.0008 by unpaired, two-tailed t-test with Welch correction (n = 3/group). Boxplot shows min to max values with line at the mean. (i) Bcl6 expression in C2C12 myotubes exposed to 33% colon-26 carcinoma (C26) conditioned versus control media for 8 hours (n = 3/group; unpaired, two-tailed t-test with Welch correction was performed) and corresponding protein blots after 8 or 24 hours. (j) Bcl6 expression in C2C12 myotubes treated with cytokines (n = 3/group), growth hormone (n = 2/group) and glucocorticoids (n = 3/group) for 8 hours. Unpaired, two-tailed t-test with Welch correction and one-way ANOVA with Dunnett’s multiple comparisons were performed. Exact p-values can be found in the source data file. All data in (a-g) and (i-j) are represented as mean + SEM. δ p < 0.05, δδ p < 0.01 for Cre+oil vs Cre-tmx; # p < 0.05, ## p < 0.01, ### p < 0.001 for Cre+oil vs Bcl6i-MKO; * p < 0.05, ** p < 0.01, *** p < 0.001 for Cre-tmx vs Bcl6i-MKO or fed vs fasted or vehicle vs treated myotubes.
