Dietary Regimens Modify Early Onset of Obesity in Mice Haploinsufficient for Rai1

Authors

Joseph T. Alaimo, Baylor College of Medicine
Natalie H. Hahn, Virginia Commonwealth University
Sureni V. Mullegama, Baylor College of Medicine
Sarah H. Elsea, Virginia Commonwealth University, Baylor College of MedicineFollow

Document Type

Article

Original Publication Date

2014

Journal/Book/Conference Title

PLOS ONE

Volume

9

DOI of Original Publication

10.1371/journal.pone.0105077

Comments

Originally published at : http://dx.doi.org/10.1371/journal.pone.0105077

Date of Submission

November 2014

Abstract

Smith-Magenis syndrome is a complex genomic disorder in which a majority of individuals are obese by adolescence. While an interstitial deletion of chromosome 17p11.2 is the leading cause, mutation or deletion of the RAI1 gene alone results in most features of the disorder. Previous studies have shown that heterozygous knockout of Rai1 results in an obese phenotype in mice and that Smith-Magenis syndrome mouse models have a significantly reduced fecundity and an altered transmission pattern of the mutant Rai1 allele, complicating large, extended studies in these models. In this study, we show that breeding C57Bl/6J Rai1+/−mice with FVB/NJ to create F1 Rai1+/− offspring in a mixed genetic background ameliorates both fecundity and Rai1 allele transmission phenotypes. These findings suggest that the mixed background provides a more robust platform for breeding and larger phenotypic studies. We also characterized the effect of dietary intake on Rai1+/− mouse growth during adolescent and early adulthood developmental stages. Animals fed a high carbohydrate or a high fat diet gained weight at a significantly faster rate than their wild type littermates. Both high fat and high carbohydrate fed Rai1+/− mice also had an increase in body fat and altered fat distribution patterns. Interestingly, Rai1+/− mice fed different diets did not display altered fasting blood glucose levels. These results suggest that dietary regimens are extremely important for individuals with Smith- Magenis syndrome and that food high in fat and carbohydrates may exacerbate obesity outcomes.

Rights

© 2014 Alaimo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Human and Molecular Genetics Publications