title: The juxtaparanodal proteins CNTNAP2 and TAG1 regulate diet-induced obesity.
abstract: Despite considerable effort, the identification of genes that regulate complex multigenic traits such as obesity has proven difficult with conventional methodologies. The use of a chromosome substitution strain-based mapping strategy based on deep congenic analysis overcame many of the difficulties associated with gene discovery and led to the finding that the juxtaparanodal proteins CNTNAP2 and TAG1 regulate diet-induced obesity. The effects of a mild Cntnap2 mutation on body weight were highly dependent on genetic background, as both obesity-promoting and obesity-resistant effects of Cntnap2 were observed on different genetic backgrounds. The more severe effect of complete TAG1 deficiency, by decreasing food intake, completely prevented the weight gain normally associated with high-fat-diet feeding. Together, these studies implicate two novel proteins in the regulation of diet-induced obesity. Moreover, as juxtaparanodal proteins have previously been implicated in various neurological disorders, our results suggest a potential genetic and molecular link between obesity and diseases such as autism and epilepsy.
authors: Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. buchnerd@umich.edu
authors: David A
authors: DA
authors: Buchner
authors: Jon M
authors: JM
authors: Geisinger
authors: Patricia A
authors: PA
authors: Glazebrook
authors: Michael G
authors: MG
authors: Morgan
authors: Sabrina H
authors: SH
authors: Spiezio
authors: Karl J
authors: KJ
authors: Kaiyala
authors: Michael W
authors: MW
authors: Schwartz
authors: Takeshi
authors: T
authors: Sakurai
authors: Andrew J
authors: AJ
authors: Furley
authors: Diana L
authors: DL
authors: Kunze
authors: Colleen M
authors: CM
authors: Croniger
authors: Joseph H
authors: JH
authors: Nadeau
mesh_terms: D050154:Adiposity / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001835:Body Weight; D033481:Chromosomes, Mammalian; D058969:Contactin 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D060467:Disease Resistance / Q000235:genetics; D002149:Energy Intake / Q000235:genetics; D004734:Energy Metabolism; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D051662:Kv1.1 Potassium Channel / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport
chemical_list: C568163:CNTNAP2 protein, mouse; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051662:Kv1.1 Potassium Channel