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

Hum Mol Genet. 2000 Dec 12;9(20):3101-10. doi: 10.1093/hmg/9.20.3101.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognition / physiology
  • Cognition Disorders / genetics
  • Disease Models, Animal
  • 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

Substances

  • Nerve Tissue Proteins
  • Nuclear Proteins
  • necdin
  • Gonadotropin-Releasing Hormone
  • Oxytocin