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The Journal of Neuroscience, March 1, 2003, 23(5):1569
BRIEF COMMUNICATION
Absence of Ndn, Encoding the Prader-Willi Syndrome-Deleted Gene necdin, Results in Congenital Deficiency of Central Respiratory Drive in Neonatal MiceJun Ren1, *, Syann Lee2, *, Silvia Pagliardini1, Matthieu Gérard3, Colin L. Stewart4, John J. Greer1, and Rachel Wevrick2 1 Centre for Neuroscience, Department of Physiology and 2 Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada T6G 2M7, 3 Division of Biochemistry and Molecular Genetics, Commissariat à l'Énergie Atomique Saclay, 91191 Gif-sur-Yvette Cedex, France, and 4 Laboratory of Cancer and Developmental Biology, National Cancer Institute-Frederick Center Research and Development Center, Frederick, Maryland 21702
necdin (Ndn) is one of a cluster of genes deleted in the neurodevelopmental disorder Prader-Willi syndrome. necdin is upregulated during neuronal differentiation and is thought to play a role in cell cycle arrest in terminally differentiated neurons. Most necdin-deficient Ndntm2Stw mutant pups carrying a targeted replacement of Ndn with a lacZ reporter gene die in the neonatal period of apparent respiratory insufficiency. We now demonstrate that the defect can be explained by abnormal neuronal activity within the putative respiratory rhythm-generating center, the pre-Bötzinger complex. Specifically, the rhythm is unstable with prolonged periods of depression of respiratory rhythmogenesis. These observations suggest that the developing respiratory center is particularly sensitive to loss of necdin activity and may reflect abnormalities of respiratory rhythm-generating neurons or conditioning neuromodulatory drive. We propose that necdin deficiency may contribute to observed respiratory abnormalities in individuals with Prader-Willi syndrome through a similar suppression of central respiratory drive.
Key words: Prader-Willi; apnea; necdin; medulla; breathing; newborn
* J.R. and S.L. contributed equally to this work.
Copyright © 2003 Society for Neuroscience 0270-6474/03/2351569-05$05.00/0
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