In contrast to transgenic models of Huntington’s disease (HD) newly available knock-in models, such as the HttQ175, recapitulate the heterozygosity present in the clinically observed pathophysiology. Here we report a longitudinal assessment of striatal metabolites using 1H-MRS and volumetry in 30+ brain regions in both male and female HttQ175 mice. Apart from a genotype-specific, progressive neurodegenerative phenotype present in both genders, we discovered an entirely novel feature in mouse models of HD, namely individuals with abnormally high glutamine (Gln) levels, whose incidence increased with mutant Htt gene dosage. In line with emerging data on a widespread peripheral metabolic perturbation in HD, we hypothesize that this excessive Gln is a consequence of disordered hepatic metabolism.
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