Fig. 6: Suppression of Il6ra expression in AP neurons attenuates cachexia in the C26 cancer model.

a A schematic of the experimental procedure. b Confocal immunohistochemical images of a coronal brain section from a representative mouse, showing the infection of AP cells with lentiviruses expressing the sgRNA (tagged with mCherry) and dCas9-KRAB-MeCP2 (tagged with FLAG). mCherry and FLAG were recognized by antibodies. The yellow cells in the overlay image indicate the dual-color labeled cells. lacZ sgRNA, n = 8, Il6ra sgRNA-4, n = 7. c Survival curves of the mice after tumor inoculation (lacZ sgRNA, n = 8, Il6ra sgRNA-4, n = 7; P = 0.000013, Mantel-Cox test). d Relationship between survival days and the fractions of Gfral⁺ neurons expressing Il6ra (n = 17 mice, R² = 0.806, F test, F = 62.34, P = 10⁻⁶ by a linear regression). e Bodyweight of individual mice relative to their bodyweight on the day of tumor inoculation. f Average bodyweight normalized to that on day -5 (lacZ sgRNA, n = 8, Il6ra sgRNA-4, n = 7; F(1,78) = 23.63, P = 9.6 × 10⁻⁶, *P = 0.012, ****P = 0.00004, two-way repeated-measures (RM) ANOVA with Sidak’s post hoc test). g Normalized cumulative food (left) and water (right) intake of the mice after tumor inoculation (lacZ sgRNA, n = 8, Il6ra sgRNA-4, n = 7; food, F(1130) = 46.9, P = 2.04 × 10⁻¹⁰; day 7, *P = 0.046, day 8, *P = 0.026, day 9, **P = 0.0046, day 10, **P = 0.003; water, F(1130) = 43.87, P = 6.6 × 10⁻¹⁰; day 8, *P = 0.03, day 9, **P = 0.005, day 10, ***P = 0.0006; two-way RM ANOVA with Sidak’s post hoc test). h Normalized cumulative food (left) and water (right) intake of the mice in the 5 days before being euthanized (lacZ sgRNA, n = 8, Il6ra sgRNA-4, n = 7; food, F(1,65) = 12.82, ***P = 0.0006; water, F(1,65) = 16.37, ***P = 0.00012; two-way RM ANOVA with Sidak’s post hoc test). AP, area postrema; NTS, nucleus tractus solitarii. Data in f, g, h are presented as mean ± s.e.m. Source data are provided as a Source Data file.