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Human Molecular Genetics, 2000, Vol. 9, No. 20 3101-3110
© 2000 Oxford University Press

Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader–Willi syndrome

Françoise Muscatelli+, Djoher Nora Abrous1, Annick Massacrier, Irène Boccaccio, Michel Le Moal1, Pierrre Cau and Harold Cremer2

INSERM U491/IBDM, Faculté de Médecine, 27 Boulevard Jean Moulin, F-13385 Marseille Cedex 5, France, 1INSERM U259, Laboratoire des Comportements Adaptatifs, Institut François Magendie, Rue Camille Saint-Saëns, F-33077 Bordeaux, France and 2LGPD/IBDM/Université de Méditerranée, Campus de Luminy, Marseille Cedex 8, France

Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with considerable clinical variability that is thought in large part to be the result of a hypothalamic defect. PWS results from the absence of paternal expression of imprinted genes localized in the 15q11–q13 region; however, none of the characterized genes has so far been shown to be involved in the etiology of PWS. Here, we provide a detailed investigation of a mouse model deficient for Necdin. Linked to the mutation, a neonatal lethality of variable penetrance is observed. Viable Necdin mutants show a reduction in both oxytocin-producing and luteinizing hormone-releasing hormone (LHRH)-producing neurons in hypothalamus. This represents the first evidence of a hypothalamic deficiency in a mouse model of PWS. Necdin-deficient mice also display increased skin scraping activity in the open field test and improved spatial learning and memory in the Morris water maze. The latter features are reminiscent of the skin picking and improved spatial memory that are characteristics of the PWS phenotype. These striking parallels in hypothalamic structure, emotional and cognitive-related behaviors strongly suggest that NECDIN is responsible for at least a subset of the multiple clinical manifestations of PWS.

+ To whom correspondence should be addressed. Tel: +33 4 9178 6894; Fax: +33 4 9180 4319; Email: muscatel@ibdm.univ-mrs.fr


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[Abstract] [Full Text] [PDF]

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Home page
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[Abstract] [Full Text] [PDF]

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[Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Lee, C. L. Walker, B. Karten, S. L. Kuny, A. A. Tennese, M. A. O'Neill, and R. Wevrick
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[Abstract] [Full Text] [PDF]

Home page
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Evidence for genetic modifiers of postnatal lethality in PWS-IC deletion mice
Hum. Mol. Genet., December 1, 2004; 13(23): 2971 - 2977.
[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

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MAGE-A1 interacts with adaptor SKIP and the deacetylase HDAC1 to repress transcription
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[Abstract] [Full Text] [PDF]

Home page
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S. Brunelli, E. Tagliafico, F. G. De Angelis, R. Tonlorenzi, S. Baesso, S. Ferrari, M. Niinobe, K. Yoshikawa, R. J. Schwartz, I. Bozzoni, et al.
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[Abstract] [Full Text] [PDF]

Home page
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A. P. Goldstone, E. L. Thomas, A. E. Brynes, G. Castroman, R. Edwards, M. A. Ghatei, G. Frost, A. J. Holland, A. B. Grossman, M. Korbonits, et al.
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J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1718 - 1726.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K.-i. Kuwako, H. Taniura, and K. Yoshikawa
Necdin-related MAGE Proteins Differentially Interact with the E2F1 Transcription Factor and the p75 Neurotrophin Receptor
J. Biol. Chem., January 16, 2004; 279(3): 1703 - 1712.
[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
T. Kaneko-Ishino, T. Kohda, and F. Ishino
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J. Biochem., June 1, 2003; 133(6): 699 - 711.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. P. Hoffman, B. L. Kidder, Z. L. Steinberg, S. Lakhani, S. Ho, H. K. Kleinman, and M. Larsen
Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms
Development, March 14, 2003; 129(24): 5767 - 5778.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Ren, S. Lee, S. Pagliardini, M. Gerard, C. L. Stewart, J. J. Greer, and R. Wevrick
Absence of Ndn, Encoding the Prader-Willi Syndrome-Deleted Gene necdin, Results in Congenital Deficiency of Central Respiratory Drive in Neonatal Mice
J. Neurosci., March 1, 2003; 23(5): 1569 - 1573.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Tcherpakov, F. C. Bronfman, S. G. Conticello, A. Vaskovsky, Z. Levy, M. Niinobe, K. Yoshikawa, E. Arenas, and M. Fainzilber
The p75 Neurotrophin Receptor Interacts with Multiple MAGE Proteins
J. Biol. Chem., December 13, 2002; 277(51): 49101 - 49104.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Kobayashi, H. Taniura, and K. Yoshikawa
Ectopic Expression of Necdin Induces Differentiation of Mouse Neuroblastoma Cells
J. Biol. Chem., October 25, 2002; 277(44): 42128 - 42135.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
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Allele-specific expression analysis by RNA-FISH demonstrates preferential maternal expression of UBE3A and imprint maintenance within 15q11- q13 duplications
Hum. Mol. Genet., July 15, 2002; 11(15): 1707 - 1718.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Sasaki, Y. Masuda, K. Iwai, K. Ikeda, and K. Watanabe
A RING Finger Protein Praja1 Regulates Dlx5-dependent Transcription through Its Ubiquitin Ligase Activity for the Dlx/Msx-interacting MAGE/Necdin Family Protein, Dlxin-1
J. Biol. Chem., June 14, 2002; 277(25): 22541 - 22546.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. P. Goldstone, U. A. Unmehopa, S. R. Bloom, and D. F. Swaab
Hypothalamic NPY and Agouti-Related Protein Are Increased in Human Illness But Not in Prader-Willi Syndrome and Other Obese Subjects
J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 927 - 937.
[Abstract] [Full Text] [PDF]

Home page
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J. L. Michaud, F. Boucher, A. Melnyk, F. Gauthier, E. Goshu, E. Levy, G. A. Mitchell, J. Himms-Hagen, and C.-M. Fan
Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus
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