Figure 4

Peripheral metabolites show alteration upon complete KMO ablation only. (a–b) Liver and spleen metabolites were analysed by HPLC in all six genotypes at 12 weeks of age. (a) In the liver, TRP remained unchanged, whereas L-KYN, AA and KYNA were all increased in WT and R6/2 mice homozygous for Kmo knockout. 3-HK was increased in R6/2 mice upon KMO ablation. QUIN was significantly increased in R6/2 mice compared to WT with no detectable signal in mice homozygous for Kmo knockout. (b) In the spleen, TRP remained unchanged, whereas L-KYN, AA, KYNA and 3-HK were all increased in both R6/2 and WT mice homozygous for Kmo knockout. QUIN was dramatically decreased in R6/2 and WT mice homozygous for Kmo knockout. Statistical analyses via one way ANOVA with Bonferroni post hoc correction; ***p ≤ 0.001, n = 3 per gender/genotype. The test statistic, degrees of freedom and p values for the ANOVA are provided in Supplementary Table S10 online. WT:KMO+/+ = WT, WT:KMO+/− = Kmo heterozygotes, WT:KMO−/− = Kmo homozygotes, R6/2:KMO+/+ = R6/2, R6/2:KMO+/− = R6/2 Kmo heterozygotes, R6/2:KMO−/− = R6/2 Kmo homozygotes, WT = wild type.