RNAseq data on single dose KMO inhibitor (CHDI-00340246) treated R6/2 mice.

Dysregulation of the kynurenine (Kyn) pathway has been associated with the progression of Huntington''s disease (HD). In particular, elevated levels of the kynurenine metabolites 3-hydroxy kynurenine (3-OH-Kyn) and quinolinic acid (Quin), have been reported in the brains of HD patients as well as in rodent models of HD. The production of these metabolites is controlled by the activity of kynurenine mono-oxygenase (KMO), a mitochondrial outer membrane enzyme which catalyzes the synthesis of 3-OH-Kyn from Kyn. Thus inhibiting KMO is expected to produce a beneficial effect in Huntington''s Disease (HD) patients, hopefully reversing their phenotype to match healthy subjects. To test this effect, we acutely treated a mouse model of HD (R6/2, a transgenic mouse model of HD which contains a human HTT gene containing 90 CAG repeats) and wild type mice with a KMO inhibitor, and separately used a mock treatment on both the transgenic mice and wild type mice. The goal of this project is to analyze the RNA-seq data and find gene expression changes associated with the KMO inhibitor Overall design: 12 wk old R6/2 and WT mice were treated per os with a single dose of 10 mg/kg CHDI-00340246 or vehicle (10% (w/v) HP-ß-CD in 50mM Citrate Buffer (pH 5.5)); striatum, cortex, cerebellum and liver tissues were collected 6 hrs following administration. N = 10 per group (5M/5F).