title: Conditional deletion of neurogenin-3 using Nkx2.1iCre results in a mouse model for the central control of feeding, activity and obesity.
abstract: The ventral hypothalamus acts to integrate visceral and systemic information to control energy balance. The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3) is required for pancreatic β-cell development and has been implicated in neuronal development in the hypothalamus. Here, we demonstrate that early embryonic hypothalamic inactivation of Ngn3 (also known as Neurog3) in mice results in rapid post-weaning obesity that is associated with hyperphagia and reduced energy expenditure. This obesity is caused by loss of expression of Pomc in Pomc- and Cart-expressing (Pomc/Cart) neurons in the arcuate nucleus, indicating an incomplete specification of anorexigenic first order neurons. Furthermore, following the onset of obesity, both the arcuate and ventromedial hypothalamic nuclei become insensitive to peripheral leptin treatment. This conditional mouse mutant therefore represents a novel model system for obesity that is associated with hyperphagia and underactivity, and sheds new light upon the roles of Ngn3 in the specification of hypothalamic neurons controlling energy balance.
authors: Division of Developmental Neurobiology, MRC-National Institute for Medical Research, London, NW7 1AA, UK.
authors: Neal
authors: N
authors: Anthwal
authors: Michelle
authors: M
authors: Pelling
authors: Suzanne
authors: S
authors: Claxton
authors: Georg
authors: G
authors: Mellitzer
authors: Caitlin
authors: C
authors: Collin
authors: Nicoletta
authors: N
authors: Kessaris
authors: William D
authors: WD
authors: Richardson
authors: Gérard
authors: G
authors: Gradwohl
authors: Siew-Lan
authors: SL
authors: Ang
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005247:Feeding Behavior; D017353:Gene Deletion; D006963:Hyperphagia / Q000097:blood / Q000150:complications; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D019426:Integrases / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D014781:Viscera / Q000473:pathology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019426:Integrases; D020738:Leptin; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011333:Pro-Opiomelanocortin; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C407737:Neurog3 protein, mouse; C484104:Nhlh2 protein, mouse; C045073:Cre recombinase
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