Studies using RNAi knockdown of dhtt have confirmed the protective role of endogenous dhtt in the presence of a polyQ expanded Htt transgene, with an inverse correlation between the dhtt:mutant Htt ratio and the severity of the disease phenotype [24].  Examination of the endogenous functions of Htt represents an alternative approach to understanding HD pathogenesis [20], [25]. The gene discussed is HTT; the disease is Huntington disease.