Mammalian Genome

, Volume 23, Issue 7, pp 431–442

The juxtaparanodal proteins CNTNAP2 and TAG1 regulate diet-induced obesity

  • David A. Buchner
  • Jon M. Geisinger
  • Patricia A. Glazebrook
  • Michael G. Morgan
  • Sabrina H. Spiezio
  • Karl J. Kaiyala
  • Michael W. Schwartz
  • Takeshi Sakurai
  • Andrew J. Furley
  • Diana L. Kunze
  • Colleen M. Croniger
  • Joseph H. Nadeau
Article

DOI: 10.1007/s00335-012-9400-8

Cite this article as:
Buchner, D.A., Geisinger, J.M., Glazebrook, P.A. et al. Mamm Genome (2012) 23: 431. doi:10.1007/s00335-012-9400-8

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.

Supplementary material

335_2012_9400_MOESM1_ESM.xlsx (43 kb)
Supplementary material 1 (XLSX 43 kb)

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • David A. Buchner
    • 1
    • 8
  • Jon M. Geisinger
    • 1
    • 9
  • Patricia A. Glazebrook
    • 3
  • Michael G. Morgan
    • 1
  • Sabrina H. Spiezio
    • 1
    • 10
  • Karl J. Kaiyala
    • 4
  • Michael W. Schwartz
    • 5
  • Takeshi Sakurai
    • 6
  • Andrew J. Furley
    • 7
  • Diana L. Kunze
    • 3
  • Colleen M. Croniger
    • 2
  • Joseph H. Nadeau
    • 1
    • 10
  1. 1.Department of GeneticsCase Western Reserve University School of MedicineClevelandUSA
  2. 2.Department of NutritionCase Western Reserve University School of MedicineClevelandUSA
  3. 3.Rammelkamp Center for Education and ResearchMetroHealth Campus of Case Western Reserve UniversityClevelandUSA
  4. 4.Department of DentistryUniversity of WashingtonSeattleUSA
  5. 5.Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, Diabetes and Obesity Center of ExcellenceUniversity of WashingtonSeattleUSA
  6. 6.Department of Pharmacology and Systems TherapeuticsMount Sinai School of MedicineNew YorkUSA
  7. 7.Department of Biomedical ScienceUniversity of Sheffield, Western BankSheffieldUK
  8. 8.Life Sciences InstituteUniversity of MichiganAnn ArborUSA
  9. 9.Department of GeneticsStanford University School of MedicineStanfordUSA
  10. 10.Institute for Systems BiologySeattleUSA

Personalised recommendations