The genetic alteration in the Gnasxl knockout mice is predicted to disrupt not only XLαs but also XLαs-N1, ALEX, XXLαs, XXLαs-N1 and ALEXX. It thus appears unlikely that the phenotype of Gnasxl knockout mice is due solely to XLαs deficiency. Nonetheless, a similar phenotype is present in mice with paternal Gnas exon 2 disruption [77-79] and in mice with a paternally inherited missense mutation in exon 6 [80, 81], thereby ruling out the involvement of ALEX, XLαs-N1, and XXLαs-N1 deficiency in the phenotypes of the Gnasxl knockout mice. Thus, it is more likely that the deficiency of XLαs and/or XXLαs underlies the findings observed in the latter mouse model, although this conclusion needs to be verified through further investigation. It is important to note that the phenotype of the Gnasxl knockout mice differs, by and large, from the phenotype of mice heterozygous for disruption of Gnas exon 1, in which Gsα, but not XLαs, is ablated [41, 82]. In fact, Gnasxl knockout mice demonstrate slightly elevated basal and isoproterenol stimulated cAMP levels in brown adipose tissue at birth [67]. These
