Postnatal Changes in the Expression Pattern of the Imprinted Signalling Protein XLαs Underlie the Changing Phenotype of Deficient Mice

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