Absence of Ndn, encoding the Prader-Willi syndrome-deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice

Jun Ren, Syann Lee, Silvia Pagliardini, Matthieu Gérard, Colin L. Stewart, John J. Greer, Rachel Wevrick

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1569-1573
Number of pages5
JournalJournal of Neuroscience
Volume23
Issue number5
StatePublished - Mar 1 2003

Fingerprint

Prader-Willi Syndrome
Genes
Respiratory Insufficiency
Respiratory Center
Neurons
Lac Operon
Multigene Family
Cell Cycle Checkpoints
Reporter Genes
necdin
Drive

Keywords

  • Apnea
  • Breathing
  • Medulla
  • necdin
  • Newborn
  • Prader-Willi

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Absence of Ndn, encoding the Prader-Willi syndrome-deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice. / Ren, Jun; Lee, Syann; Pagliardini, Silvia; Gérard, Matthieu; Stewart, Colin L.; Greer, John J.; Wevrick, Rachel.

In: Journal of Neuroscience, Vol. 23, No. 5, 01.03.2003, p. 1569-1573.

Research output: Contribution to journalArticle

Ren, Jun ; Lee, Syann ; Pagliardini, Silvia ; Gérard, Matthieu ; Stewart, Colin L. ; Greer, John J. ; Wevrick, Rachel. / Absence of Ndn, encoding the Prader-Willi syndrome-deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 5. pp. 1569-1573.
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