Gain-of-function effects of mhtt are effectively assessed in the R6/2 mouse model of HD, which expresses an N-terminal fragment of mhtt in the presence of normal Htt protein and exhibits a phenotype of early striatal MSN degeneration and locomotor dysfunction (Mangiarini et al., 1996; Stack et al., 2007; Samadi et al., 2013). This evidence concerns the gene HTT and Huntington disease.