Thus, Rai1+/− mice failed to recapitulate the sleep rhythm disturbance in SMS patients likely due to (1) intrinsic differences in the circadian time-keeping system between nocturnal and diurnal mammals, (2) melatonin deficiency, and (3) distinct responses to light independent from the circadian drive, which can all be addressed using a diurnal rodent model. Here, RAI1 is linked to Smith-Magenis syndrome.