Respiratory control abnormalities in necdinnull mice: implications for the pathogenesis of Prader-Willi syndrome

  • John J. Greer
  • Rachel Wevrick


Obstructive Sleep Apnea Dorsal Root Ganglion Central Sleep Apnea Respiratory Rhythm Respiratory Dysfunction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Arens R, Gozal D, Omlin K, Livingston FR, Liu J, Keens TG, Ward SL (1994) Hypoxic and hypercapnic ventilatory responses in Prader-Willi syndrome. J Appl Physiol 77: 2224-2230PubMedGoogle Scholar
  2. 2.
    Arens R, Gozal D, Burrell BC, Bailey SL, Bautista DB, Keens TG, Ward SL (1996) Arousal and cardiorespiratory responses to hypoxia in Prader-Willi syndrome. Am J Respir Crit Care 153: 283-287Google Scholar
  3. 3.
    Barker PA, Salehi A (2002) The MAGE proteins: Emerging roles in cell cycle progression, apoptosis, and neurogenetic disease. J Neurosci Res 67: 705-712PubMedCrossRefGoogle Scholar
  4. 4.
    Bragason BT, Palsdottir A (2005) Interaction of PrP with NRAGE, a protein involved in neuronal apoptosis. Mol Cell Neurosci 29: 232-244PubMedCrossRefGoogle Scholar
  5. 5.
    Carrel AL, Myers SE, Whitman BY, Allen DB (2001) Sustained benefits of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome are dose-dependent. J Pediatr Endocrinol Metab 14: 1097-1105PubMedGoogle Scholar
  6. 6.
    Clift S, Dahlitz M, Parkes JD (1994) Sleep apnoea in the Prader-Willi syndrome. J Sleep Res 3: 121-126PubMedCrossRefGoogle Scholar
  7. 7.
    Feldman JL, Del Negro CA (2006) Looking for inspiration: new perspectives on respiratory rhythm. Nat Rev Neurosci 7: 232-241PubMedCrossRefGoogle Scholar
  8. 8.
    Funk GD, Smith JC, Feldman JL (1993) Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids. J Neurophysiol 70: 1497-1515PubMedGoogle Scholar
  9. 9.
    Gerard M, Hernandez L, Wevrick R, Stewart C (1999) Disruption of the mouse necdin gene results in early postnatal lethality:a model for neonatal distress in Prader-Willi syndrome. Nat Genet 23: 199-202PubMedCrossRefGoogle Scholar
  10. 10.
    Goldstone AP (2004) Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab 15: 12-20PubMedCrossRefGoogle Scholar
  11. 11.
    Gozal D, Arens R, Omlin KJ, Ward SL, Keens TG (1994) Absent peripheral chemosensitivity in Prader-Willi syndrome. J Appl Physiol 77: 2231-2236PubMedGoogle Scholar
  12. 12.
    Greer JJ, Smith JC, Feldman JL (1991) Role of excitatory amino acids in the generation and transmission of respiratory drive in neonatal rat. J Physiol 437: 727749Google Scholar
  13. 13.
    Greer JJ, Smith JC, Feldman JL (1992) Respiratory and locomotor patterns generated in the fetal rat brain stem-spinal cord in vitro. J Neurophysiol 67: 996-999PubMedGoogle Scholar
  14. 14.
    Greer JJ, Funk GD, Ballanyi K (2006) Preparing for the first breath: Prenatal maturation of respiratory neural control. J Physiol 570: 437-444PubMedCrossRefGoogle Scholar
  15. 15.
    Hayashi M, Itoh M, Kabasawa Y, Hayashi H, Satoh J, Morimatsu Y (1992) A neuropathological study of a case of the Prader-Willi syndrome with an interstitial deletion of the proximal long arm of chromosome 15. Brain Dev 14: 58-62PubMedGoogle Scholar
  16. 16.
    Kobayashi M, Taniura H, Yoshikawa K (2002) Ectopic expression of necdin induces differentiation of mouse neuroblastoma cells. J Biol Chem 277: 42128-42135Google Scholar
  17. 17.
    Kuwako K, Hosokawa A, Nishimura I, Uetsuki T, Yamada M, Nada S, Okada M, Yoshikawa K (2005) Disruption of the paternal necdin gene diminishes TrkA signaling for sensory neuron survival. J Neurosci 25: 7090-7099PubMedCrossRefGoogle Scholar
  18. 18.
    Kuwako K, Taniura H, Yoshikawa K (2004) Necdin-related MAGE proteins differentially interact with the E2F1 transcription factor and the p75 neurotrophin receptor. J Biol Chem 279: 1703-1712PubMedCrossRefGoogle Scholar
  19. 19.
    Jay P, Rougeulle C, Massacrier A, Moncla A, Mattei MG, Malzac P, Roeckel N, Taviaux S, Lefranc JL, Cau P, Berta P, Lalande M, Muscatelli F (1997) The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region. Nat Genet 17: 357-361PubMedCrossRefGoogle Scholar
  20. 20.
    Lagercrantz H (1987) Neuromodulators and respiratory control during development. Trends Neurosci 10: 368-372CrossRefGoogle Scholar
  21. 21.
    Lee S, Walker CL, Karten B, Kuny SL, Tennese AA, O’Neill MA, Wevrick R (2005) Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. Hum Mol Genet 14: 627-637PubMedCrossRefGoogle Scholar
  22. 22.
    L’Hermine AC, Aboura A, Brisset S, Cuisset L, Castaigne V, Labrune P, Frydman R, Tachdjian G (2003) Fetal phenotype of Prader-Willi syndrome due to maternal disomy for chromosome 15. Prenat Diagn 23: 938-943PubMedCrossRefGoogle Scholar
  23. 23.
    Lindgren AC, Hellstrom LG, Ritzen EM, Milerad J (1999) Growth hormone treatment increases CO2 response, ventilation and central inspiratory drive in children with Prader-Willi syndrome. Eur J Pediatr 158: 936-940PubMedCrossRefGoogle Scholar
  24. 24.
    Livingston FR, Arens R, Bailey SL, Keens TG, Ward SL (1995) Hypercapnic arousal responses in Prader-Willi syndrome. Chest 108: 1627-1631PubMedGoogle Scholar
  25. 25.
    MacDonald HR, Wevrick R (1997) The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse. Hum Mol Genet 6: 1873-1878PubMedCrossRefGoogle Scholar
  26. 26.
    Manni R, Politini L, Nobili L, Ferrillo F, Livieri C, Veneselli E, Biancheri R, Martinetti M, Tartara A (2001) Hypersomnia in the Prader-Willi syndrome: clinical-electrophysiological features and underlying factors. Clin Neurophysiol 112: 800-805PubMedCrossRefGoogle Scholar
  27. 27.
    Maruyama K, Usami M, Aizawa T, Yoshikawa K (1991) A novel brain-specific mRNA encoding nuclear protein (necdin) expressed in neurally differentiated embryonal carcinoma cells. Biochem Biophys Res Commun 178: 291-296PubMedCrossRefGoogle Scholar
  28. 28.
    Menendez AA (1999) Abnormal ventilatory responses in patients with Prader-Willi syndrome. Eur J Pediatr 158: 941-942PubMedCrossRefGoogle Scholar
  29. 29.
    Moss IR, Inman JG (1989) Neurochemicals and respiratory control during development. J App Physiol 67: 1-13Google Scholar
  30. 30.
    Muscatelli F, Abrous DN, Massacrier A, Boccaccio I, Moal ML, Cau P, Cremer H (2000) Disruption of the mouse necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. Hum Mol Genet 9: 3101-3110PubMedCrossRefGoogle Scholar
  31. 31.
    Nagai T, Obata K, Tonoki H, Temma S, Murakami N, Katada Y, Yoshino A, Sakazume S, Takahashi E, Sakuta R, Niikawa N (2005) Cause of sudden, unexpected death of Prader-Willi syndrome patients with or without growth hormone treatment. Am J Med Genet 136: 45-48CrossRefPubMedGoogle Scholar
  32. 32.
    Nicholls RD, Knepper JL (2001) Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes. Annu Rev Genomics Hum Genet 2: 153-175PubMedCrossRefGoogle Scholar
  33. 33.
    33. Nixon GM, Brouillette RT (2002) Sleep and breathing in Prader-Willi syndrome. Pediatr Pulmonol 34: 209-217PubMedCrossRefGoogle Scholar
  34. 34.
    Pagliardini S, Ren J, Wevrick R, Greer JJ (2005) Developmental abnormalities of neuronal structure and function in prenatal mice lacking the Prader-Willi gene necdin. Am J Pathol 167: 175-191PubMedGoogle Scholar
  35. 35.
    Ren J, Lee S, Pagliardini S, Gerard C L, Stewart CL, Greer JJ, Wevrick R (2003) Absence of Ndn, encoding the Prader-Willi syndrome-deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice. J Neurosci 23: 1569-1573PubMedGoogle Scholar
  36. 36.
    Ren J, Poon BY, Tang Y, Funk GD, Greer JJ (2006) Ampakines alleviate respiratory depression in rats. Am J Resp Crit Care 174: 1384-1391CrossRefGoogle Scholar
  37. 37.
    Salehi AH, Roux PP, Kubu CJ, Zeindler C, Bhakar A, Tannis LL, Verdi JM, Barker PA (2000) NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis. Neuron 27: 279-288PubMedCrossRefGoogle Scholar
  38. 38.
    Salehi AH, Xanthoudakis S, Barker PA (2002) NRAGE, a p75 neurotrophin receptor-interacting protein, induces caspase activation and cell death through a JNK-dependent mitochondrial pathway. J Biol Chem 277: 48043-48050.PubMedCrossRefGoogle Scholar
  39. 39.
    Schluter B, Buschatz D, Trowitzsch E, Aksu F, Andler W (1997) Respiratory control in children with Prader-Willi syndrome. Eur J Pediatr 156: 65-68PubMedGoogle Scholar
  40. 40.
    Schrander-Stumpel CT, Curfs LM, Sastrowijoto P, Cassidy SB, Schrander JJ, Fryns JP (2004) Prader-Willi syndrome: causes of death in an international series of 27 cases. Am J Med Genet 124: 333-338CrossRefGoogle Scholar
  41. 41.
    Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL (1991) Pre-Bötzinger Complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254: 726-728PubMedCrossRefGoogle Scholar
  42. 42.
    Stevenson DA, Anaya TM, Clayton-Smith J, Hall BD, Van Allen MI, Zori RT, Zackai EH, Frank G, Clericuzio CL (2004) Unexpected death and critical illness in Prader-Willi syndrome: report of ten individuals. Am J Med Genet 124: 158-164CrossRefGoogle Scholar
  43. 43.
    Sutcliffe JS, Han M, Christian SL, Ledbetter DH (1997) Neuronally-expressed necdin gene: an imprinted candidate gene in Prader-Willi syndrome. Lancet 350: 1520-1521PubMedCrossRefGoogle Scholar
  44. 44.
    Takazaki R, Nishimura I, Yoshikawa K (2002) Necdin is required for terminal differentiation and survival of primary dorsal root ganglion neurons. Exp Cell Res 277: 220-232PubMedCrossRefGoogle Scholar
  45. 45.
    Tcherpakov M, Bronfman FC, Conticello SG, Vaskovsky A, Levy Z, Niinobe M, Yoshikawa K, Arenas E, Fainzilber M (2002) The p75 neurotrophin receptor interacts with multiple MAGE proteins. J Biol Chem 277: 49101-49104PubMedCrossRefGoogle Scholar
  46. 46.
    Tsai TF, Armstrong D, Beaudet AL (1999) Necdin-deficient mice do not show lethality or the obesity and infertility of Prader-Willi syndrome. Nat Genet 22: 1516Google Scholar
  47. 47.
    Wharton RH, Loechner KJ (1996) Genetic and clinical advances in Prader-Willi syndrome. Curr Opin Pediatr 8: 618-624PubMedCrossRefGoogle Scholar
  48. 48.
    Zanella S, Roux JC, Muscatelli F, Hilaire G (2006) Necdin gene, respiratory disturbances and Prader-Willi Syndrome. Xth Oxford Conference Lake Louise Canada 17-24 September: p62Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • John J. Greer
    • 1
  • Rachel Wevrick
    • 2
  1. 1.Department of PhysiologyUniversity of AlbertaEdmontonCanada
  2. 2.Department of Medical GeneticsUniversity of AlbertaEdmontonCanada

Personalised recommendations