The alternatively spliced trimeric G-protein subunit XLas, which is involved in @entity268 signalling, is encoded by the @entity12820 transcript of the imprinted @entity12820 locus. XLas deficient @entity19 show neonatal feeding problems, leanness, @entity1806 and a high mortality rate. Mutants that survive to weaning age develop into healthy and fertile adults, which remain lean despite elevated food intake. The adult metabolic phenotype can be attributed to increased energy expenditure, which appears to be caused by elevated sympathetic nervous system activity. To better understand the changing phenotype of @entity12820 deficient @entity19 , we compared XLas expression in neonatal versus adult tissues, analysed its co-localisation with neural markers and characterised changes in the nutrient-sensing mTOR1-S6K pathway in the hypothalamus. Using a newly generated conditional @entity12820 lacZ gene trap line and immunohistochemistry we identified various types of muscle, including smooth muscle cells of blood vessels, as the major peripheral sites of expression in neonates. Expression in all muscle tissues was silenced in adults. While @entity12820 expression in the central nervous system was also developmentally silenced in some midbrain nuclei, it was upregulated in the preoptic area, the medial amygdala, several hypothalamic nuclei (e.g. arcuate, dorsomedial, lateral and paraventricular nuclei) and the nucleus of the solitary tract. Furthermore, expression was detected in the ventral medulla as well as in motoneurons and a subset of sympathetic preganglionic neurons of the spinal cord. In the arcuate nucleus of @entity12820 -deficient @entity19 we found reduced activity of the nutrient sensing mTOR1-S6K signalling pathway, which concurs with their metabolic status. The expression in these brain regions and the @entity2495 phenotype of adult @entity12820 -deficient @entity19 imply an inhibitory function of XLas in energy expenditure and sympathetic outflow. By contrast, the neonatal phenotype of mutant @entity19 appears to be due to a transient role of XLas in muscle tissues.

Postnatal changes in the expression pattern of the imprinted signalling protein XLas underlie the changing phenotype of deficient XXXX .

@entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity12820 :: ('14683(Tax:10090)', 'Gene') :: ['Gnas', 'Gnasxl'] @entity2495 :: ('MESH:C565498', 'Disease') :: ['hypermetabolic'] @entity1806 :: ('MESH:D014593', 'Disease') :: ['inertia']
@entity19 :: (10090,Species) :: ['mice']
