Fig. 2

Deletion of Gba2 in gba1 KO medaka did not rescue their phenotypes. a A Kaplan–Meier plot showed that the deletion of Gba2 in gba1 KO medaka shortened the lifespan (n = 15–41 for each genotype). A Log-rank (Mantel-Cox) test was performed. b Representative TH immunohistochemical staining of the middle diencephalic dopaminergic neurons in WT, gba1 KO, and gba1/gba2 DKO medaka at 3 mpf. c The number of TH-positive (TH⁺) neurons in the middle diencephalon at 3 mpf. The number of TH⁺ neurons was decreased in gba1/gba2 DKO medaka compared with WT medaka but did not markedly differ between gba1/gba2 DKO and gba1 KO medaka (n = 6–10 for each genotype). A one-way ANOVA with Tukey's multiple comparison test was performed. d The number of TH⁺ neurons in the locus coeruleus at 3 mpf. The number of TH⁺ neurons was decreased in gba1/gba2 DKO medaka compared with WT medaka but did not differ markedly between gba1/gba2 DKO and gba1 KO medaka (n = 4–10 for each genotype). A one-way ANOVA with Tukey's multiple comparison test was performed. e qRT-PCR analysis of TNF-α mRNA in the brains of 3 mpf medaka. TNF-α mRNA levels were normalized to β-actin mRNA. The TNF-α mRNA levels did not differ markedly between gba1/gba2 DKO and gba1 KO medaka (n = 6 for each genotype). Dunn’s multiple comparisons test was performed. f qRT-PCR analysis of ApoE-b mRNA in the brains of 3 mpf medaka. The ApoE-b mRNA levels were normalized to β-actin mRNA. The amount of ApoE-b mRNA was increased in gba1/gba2 DKO medaka compared with WT medaka but did not differ markedly between gba1/gba2 DKO and gba1 KO medaka (n = 6 for each genotype). A one-way ANOVA with Tukey's multiple comparison test was performed. n.s. not significant, ****p < 0.0001. The bars indicate mean ± SEM