A novel form of ciliopathy underlies hyperphagia and obesity in Ankrd26 knockout mice

Brain Struct Funct. 2015;220(3):1511-28. doi: 10.1007/s00429-014-0741-9. Epub 2014 Mar 16.

Abstract

Human ciliopathies are genetic disorders caused by mutations in genes responsible for the formation and function of primary cilia. Some are associated with hyperphagia and obesity (e.g., Bardet-Biedl Syndrome, Alström Syndrome), but the mechanisms underlying these problems are not fully understood. The human gene ANKRD26 is located on 10p12, a locus that is associated with some forms of hereditary obesity. Previously, we reported that disruption of this gene causes hyperphagia, obesity and gigantism in mice. In the present study, we looked for the mechanisms that induce hyperphagia in the Ankrd26-/- mice and found defects in primary cilia in regions of the central nervous system that control appetite and energy homeostasis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Acetylcholine / blood
  • Animals
  • Brain / metabolism
  • Brain / ultrastructure
  • Cilia / metabolism
  • Cilia / ultrastructure
  • Corticosterone / blood
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Hyperphagia / genetics*
  • Hyperphagia / pathology*
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / ultrastructure*
  • Obesity / genetics*
  • Obesity / pathology*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Paraventricular Hypothalamic Nucleus / ultrastructure*
  • Receptor, Melanocortin, Type 4 / metabolism
  • Receptors, Leptin / metabolism
  • Stress, Physiological
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Ankrd26 protein, mouse
  • DNA-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • MC4R protein, mouse
  • Receptor, Melanocortin, Type 4
  • Receptors, Leptin
  • Transcription Factors
  • Acetylcholine
  • Corticosterone