Fig. 5: Hsd17B4-deficient mice exhibit a ciliopathy-like pathology.
From: HSD17B4 deficiency causes dysregulation of primary cilia and is alleviated by acetyl-CoA
a Western blot analysis confirmed the downregulation of Hsd17B4 in Hsd17B4−/− mice (n = 3). b Growth retardation was assessed by imaging 11-week-old mice and measuring body weight from 3-week-old mice (Hsd17B4+/+ n = 9; Hsd17B4−/− n = 7). Data are presented as the mean ± SEM. Statistical analysis was performed using two-way ANOVA with multiple comparisons. Scale bars, 1 cm. c Kaplan-Meier survival curves comparing Hsd17B4+/+ (n = 25) and Hsd17B4−/− mice (n = 30) were analyzed using the Log-rank (Mantel-Cox) tests (p < 0.0001). d Representative images (n = 3) of H&E staining revealed reduced cerebellar volume, malformed lobules, and thinner molecular layers in Hsd17B4−/− mice. Scale bars, 500, 50, and 20 μm. e Molecular layer thickness was quantified in Hsd17B4+/+ (n = 7) and Hsd17B4−/− (n = 6) mice (p < 0.0001). Data are presented as the mean ± SEM. f Motor function was evaluated using the rota-rod test in 9- and 11-week-old mice. Box plots represent the interquartile range (25th–75th percentile), median (central line), and minimum/maximum values (whiskers) [9-week-old Hsd17B4+/+ (n = 6) Min = 59, Max = 300, Median = 280.5; Hsd17B4−/− (n = 5) Min = 18, Max = 190, Median = 105; 11-week-old Hsd17B4+/+(n = 6) Min = 24, Max = 300, Median = 196; Hsd17B4−/− (n = 3) Min = 1, Max = 131, Median = 1]. [Hsd17B4+/+ vs. Hsd17B4−/−; 9 weeks p = 0.0006, 11 weeks p = 0.0014]. g–j. Immunofluorescence staining for primary cilia (ARL13B, green, white arrow; DAPI, blue) was performed in granular (Scale bar, 2 μm) and Purkinje (Scale bar, 20 μm) layers. Purkinje cells were counterstained with anti-calbindin (red). Data are presented as mean ± SEM (n = 3, independent biological replicates). [Hsd17B4+/+ vs. Hsd17B4−/− Ciliated cells: p = 0.0078 (h), p = 0.0010 (j); Cilium length: p < 0.0001 (h, j)]. Statistical analysis was performed using a two-tailed unpaired t-test (e–j). k Western blot confirmed HSD17B4 expression in the cerebellum from three independent experiments. Source data are provided in the Source Data file.
