Fig. 6: Acetate administration rescues ciliopathy-like phenotypes in Hsd17B4-deficient mice.
From: HSD17B4 deficiency causes dysregulation of primary cilia and is alleviated by acetyl-CoA
a Birth rates of Hsd17B4+/+ and Hsd17B4−/− mice were assessed with and w/o acetate administration (Cont n = 108; Acetate n = 57). b Survival rates were monitored for up to 12 weeks, showing a significant improvement in acetate-supplemented Hsd17B4−/− mice (n = 13) compared to untreated mice (n = 18). Kaplan-Meier survival curves were analyzed using the Log-rank (Mantel-Cox) test (Hsd17B4+/+; Cont n = 19, Acetate n = 12; p = 0.0403). c H&E staining revealed reduced cerebellar volume and malformed lobules in Hsd17B4−/− mice. d Motor function was evaluated using the rota-rod test in 11-week-old mice. Acetate-treated Hsd17B4−/− mice exhibited improved performance compared to untreated mice. Box plots represent the interquartile range (25th–75th percentile), median (line), and minimum/maximum values (whisker) [Hsd17B4+/+: Cont (n = 12) Min = 38, Max = 300, Median = 294; Acetate (n = 11) Min = 100, Max = 300, Median = 298; Hsd17B4−/−: Cont (n = 6) Min = 1, Max = 41, Median = 21; Acetate (n = 9) Min = 37, Max = 288, Median = 109]. [Hsd17B4+/+ vs. Hsd17B4−/− p < 0.0001; Hsd17B4−/− Cont vs. Acetate p = 0.006]. e Purkinje cell dysplasia in cerebellar lobule IV/V of Hsd17B4−/− mice was significantly improved by acetate administration (calbindin, red; DAPI, blue; Scale bar, 50 μm) [Hsd17B4+/+ vs. Hsd17B4−/− p < 0.0001; Hsd17B4−/− Cont vs. Acetate p = 0.0115]. f–i Immunostaining of primary cilia in Purkinje and granular cells (calbindin, red; ARL13B, green; DAPI, blue) showed increased ciliary formation and elongation following acetate treatment [Ciliated cells: Hsd17B4+/+ vs. Hsd17B4−/− p = 0.0319 (g), p = 0.0120 (i); Hsd17B4−/− Cont vs. Acetate p = 0.0088 (g), p = 0.0127 (i); Cilium length: Hsd17B4+/+ vs. Hsd17B4−/− p < 0.0001 (g, i); Hsd17B4−/− Cont vs. Acetate p < 0.0001 (g, i)]. Scale bar, 20 μm. j, k Western blot analysis of primary cilia-mediated signaling [Hsd17B4+/+ vs. Hsd17B4-/-; GLI2 p = 0.0002, p-Smad2/3 p = 0.0265, p-AKT p = 0.0475; Hsd17B4−/− Cont vs. Acetate; GLI2 p = 0.0012]. Statistical analysis was performed using one-way ANOVA followed by Tukey’s multiple comparisons test (d–k). Data are presented as mean ± SEM (n = 3, independent biological replicates). Source data are provided in the Source Data file.
