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

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 th...

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Published in:	Human molecular genetics Vol. 9; no. 20; pp. 3101 - 3110
Main Authors:	MUSCATELLI, Francoise, DJOHER NORA ABROUS, MASSACRIER, Annick, BOCCACCIO, Irène, LE MOAL, Michel, CAU, Pierrre, CREMER, Harold
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 12-12-2000 Oxford Publishing Limited (England)
Subjects:	Animals Biological and medical sciences Classical genetics, quantitative genetics, hybrids Cognition - physiology Cognition Disorders - genetics Disease Models, Animal Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Gonadotropin-Releasing Hormone - metabolism Hypothalamus - metabolism Hypothalamus - physiology Mice Mice, Knockout Nerve Tissue Proteins - deficiency Nerve Tissue Proteins - genetics Nerve Tissue Proteins - physiology Neurons - physiology Nuclear Proteins - deficiency Nuclear Proteins - genetics Nuclear Proteins - physiology Oxytocin - metabolism Prader-Willi Syndrome - genetics Prader-Willi Syndrome - psychology Psychomotor Performance - physiology Vertebrata Nervous system diseases Rodentia Histology Mental retardation Genital diseases Genetic disease Vertebrata Phenotype Mammalia Gene Mouse Behavioral analysis Etiology Mutation Complex syndrome Prader Labhart Willi syndrome
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0964-6906 1460-2083 1460-2083
DOI:	10.1093/hmg/9.20.3101