title: Dietary regimens modify early onset of obesity in mice haploinsufficient for Rai1.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Alaimo
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Hahn
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Natalie H
authors.initials: NH
authors.lastname: Hahn
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Sureni V
authors.initials: SV
authors.lastname: Mullegama
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Elsea
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D050218:Body Fat Distribution; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D057895:Haploinsufficiency; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D058496:Smith-Magenis Syndrome / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; C502844:Rai1 protein, mouse; D015534:Trans-Activators