RAI1 and obesity due to melanocortin 4 receptor deficiency: This hypothesis is supported by murine models of SMS, where deletion of a 2 Mb region containing the murine Rai1 gene6, 7 or targeted inactivation of the Rai1 gene8, 9 reproduce many of the clinical phenotypes observed in SMS patients, including craniofacial abnormalities, seizures, abnormal circadian rhythm, and obesity.