Absence ofNdn, Encoding the Prader-Willi Syndrome-Deleted Genenecdin, Results in Congenital Deficiency of Central Respiratory Drive in Neonatal Mice

摘要: necdin ( Ndn ) is one of a cluster genes deleted in the neurodevelopmental disorder Prader-Willi syndrome. upregulated during neuronal differentiation and thought to play role cell cycle arrest terminally differentiated neurons. Most -deficient tm2Stw mutant pups carrying targeted replacement with lacZ reporter gene die neonatal period apparent respiratory insufficiency. We now demonstrate that defect can be explained by abnormal activity within putative rhythm-generating center, pre-Botzinger complex. Specifically, rhythm unstable prolonged periods depression rhythmogenesis. These observations suggest developing center particularly sensitive loss may reflect abnormalities neurons or conditioning neuromodulatory drive. propose deficiency contribute observed individuals syndrome through similar suppression central