Alterations in the brain’s histamine modulatory system have been implicated as a contributor to the development of tics and of TS by a series of genetic studies.6, 9, 10 The Hdc knockout mouse recapitulates a rare but high-penetrance genetic cause of TS and constitutes a promising model of its pathophysiology.6, 7Hdc-KO mice exhibit repetitive behavioral pathology, DA dysregulation, and altered markers of cellular activity and intracellular signaling in the striatum.7, 14, 43, 44. Here, HDC is linked to Timothy syndrome.