GNAS and obesity due to melanocortin 4 receptor deficiency: For example, heterozygous mice carrying maternally-derived knockout mutations within exon 2 of the Gnas gene (an exon common to all transcripts produced within the Gnas domain) display severe obesity, increased insulin sensitivity and increased perinatal mortality, while heterozygotes carrying a paternally-derived exon 2 knockout mutations (indicative of a loss of Gnasxl transcripts) also displayed increased perinatal mortality, greatly increased insulin sensitivity, hypermetabolism and reduced adiposity; homozygous individuals were embryonically lethal [59-61].