Necdin gene, respiratory disturbances and Prader-Willi syndrome.
Prader-Willi Syndrome (PWS) is a complex neurogenetic disease with various symptoms, including breathing deficits and possible alteration of serotonin (5HT) metabolism. As PWS results from the absence of paternal expression of several imprinted genes among which NECDIN (Ndn), we examined whether Ndn deficiency in mice induced breathing and 5HT deficits. In vivo, Ndn-deficient mice (Ndn-/-) had irregular breathing, severe apneas and blunted respiratory response to hypoxia. In vitro, medullary preparations from Ndn-/- neonates produced a respiratory-like rhythm that was highly irregular, frequently interrupted and abnormally regulated by central hypoxia. In wild type (wt) and Ndn-/- neonates, immunohistofluorescence and biochemistry revealed that medullary 5HT neurons expressed Ndn in wt and that the medulla contained abnormally high levels of 5HT in Ndn-/-. Thus, our preliminary results fully confirm a primary role of Ndn in PWS, revealing that Ndn-deficiency in mice induces respiratory and 5HT alterations reminiscent of PWS.
Zanella
Sébastien
S
CNRS, UMR 6153, 280 boulevard Sainte Marguerite, 13009 Marseille, France.
Barthelemy
Magali
M
Muscatelli
Françoise
F
Hilaire
Gérard
G
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000503:physiopathology; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics*; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics*; D011218:Prader-Willi Syndrome / Q000235:genetics*; D012120:Respiration Disorders / Q000235:genetics*; D012701:Serotonin / Q000502:physiology
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C069766:necdin; D012701:Serotonin