Chromosomal mapping of excessive physical activity in mice in response to a restricted feeding schedule

Gelegen, C.; Pjetri, E.; Campbell, I.C.; Collier, D.A.; Oppelaar, H.; Kas, M.J.H.

doi:10.1016/j.euroneuro.2009.10.001

« Previous Next »European Neuropsychopharmacology
Volume 20, Issue 5 , Pages 317-326, May 2010

Chromosomal mapping of excessive physical activity in mice in response to a restricted feeding schedule

C. Gelegen
- Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, Utrecht, The Netherlands
- Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK
E. Pjetri
- Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, Utrecht, The Netherlands
I.C. Campbell
- Institute of Psychiatry, Department of Neuroscience, King's College London, UK
D.A. Collier
- Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK
H. Oppelaar
- Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, Utrecht, The Netherlands
M.J.H. Kas
- Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, Utrecht, The Netherlands
- Corresponding author. Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Tel.: +31 88 756 8179; fax: +31 88 756 9032.

Received 12 June 2009; received in revised form 2 September 2009; accepted 4 October 2009. published online 09 November 2009.

Abstract

Excessive physical activity plays an important role in the progression of anorexia nervosa (AN) by accelerating weight loss during dietary restriction. To search for mechanisms underlying this trait, a panel of mouse chromosome substitution strains derived from C57BL/6J and A/J strains was exposed to a scheduled feeding paradigm and to voluntary running wheel (RW) access. Here, we showed that A/J chromosomes 4, 12 and 13 contribute to the development of a disrupted RW activity in response to daily restricted feeding. This pattern is characterized by intense RW activity during the habitual rest phase and leads to accelerated body weight loss. Regions on mouse chromosomes 4, 12 and 13 display homology with regions on human chromosomes linked with anxiety and obsessionality in AN cohorts. Therefore, our data open new roads for interspecies genetic studies of AN and for unraveling novel mechanisms and potential effective treatment strategies for these neurobehavioral traits.

Keywords: Running wheel activity, Chromosome substitution strains, Anorexia nervosa, Food restriction, Hyperactivity, Body weight