Genetic Resistance to Diet-induced Obesity in Chromosome Substitution Strains of Mice

Overview

Journal Mamm Genome

Specialty Genetics

Date 2010 Feb 4

PMID 20127486

Citations 22

Authors

Lindsay C Burrage

Annie E Baskin-Hill

David S Sinasac

Jonathan B Singer

Colleen M Croniger

Andrew Kirby

E J Kulbokas

Mark J Daly

Eric S Lander

Karl W Broman

Joseph H Nadeau

Affiliations

Soon will be listed here.

Abstract

Discovery of genes that confer resistance to diseases such as diet-induced obesity could have tremendous therapeutic impact. We previously demonstrated that the C57BL/6J-Chr(A/J)/NaJ panel of chromosome substitution strains (CSSs) is a unique model for studying resistance to diet-induced obesity. In the present study, three replicate CSS surveys showed remarkable consistency, with 13 A/J-derived chromosomes reproducibly conferring resistance to high-fat-diet-induced obesity. Twenty CSS intercrosses, one derived from each of the 19 autosomes and chromosome X, were used to determine the number and location of quantitative trait loci (QTLs) on individual chromosomes and localized six QTLs. However, analyses of mean body weight in intercross progeny versus C57BL/6J provided strong evidence that many QTLs discovered in the CSS surveys eluded detection in these CSS intercrosses. Studies of the temporal effects of these QTLs suggest that obesity resistance was dynamic, with QTLs acting at different ages or after different durations of diet exposure. Thus, these studies provide insight into the genetic architecture of complex traits such as resistance to diet-induced obesity in the C57BL/6J-Chr(A/J)/NaJ CSSs. Because some of the QTLs detected in the CSS intercrosses were not detected using a traditional C57BL/6J x A/J intercross, our results demonstrate that surveys of CSSs and congenic strains derived from them are useful complementary tools for analyzing complex traits.

Citing Articles

Unlocking metabolic insights with mouse genetic diversity.

Masson S, Cutler H, James D EMBO J. 2024; 43(21):4814-4821.

PMID: 39284908 PMC: 11535531. DOI: 10.1038/s44318-024-00221-2.

The impact of maternal high-fat diet on offspring neurodevelopment.

Urbonaite G, Knyzeliene A, Bunn F, Smalskys A, Neniskyte U Front Neurosci. 2022; 16:909762.

PMID: 35937892 PMC: 9354026. DOI: 10.3389/fnins.2022.909762.

Comparative study of liver injury induced by high-fat methionine- and choline-deficient diet in ICR mice originating from three different sources.

Lee S, Kwak J, Kim S, Jeong T, Son S, Kim J Lab Anim Res. 2020; 35:15.

PMID: 32257903 PMC: 7081597. DOI: 10.1186/s42826-019-0016-y.

Low Citrate Synthase Activity Is Associated with Glucose Intolerance and Lipotoxicity.

Alhindi Y, VaanHolt L, Al-Tarrah M, Gray S, Speakman J, Hambly C J Nutr Metab. 2019; 2019:8594825.

PMID: 30944739 PMC: 6421790. DOI: 10.1155/2019/8594825.

A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques.

Florek K, Kamlangdee A, Mutschler J, Kingstad-Bakke B, Schultz-Darken N, Broman K PLoS One. 2017; 12(8):e0181738.

PMID: 28771513 PMC: 5542451. DOI: 10.1371/journal.pone.0181738.

References

Schelbert K . Comorbidities of obesity. Prim Care. 2009; 36(2):271-85. DOI: 10.1016/j.pop.2009.01.009. View

Koza R, Nikonova L, Hogan J, Rim J, Mendoza T, Faulk C . Changes in gene expression foreshadow diet-induced obesity in genetically identical mice. PLoS Genet. 2006; 2(5):e81. PMC: 1464831. DOI: 10.1371/journal.pgen.0020081. View

Altshuler D, Daly M, Lander E . Genetic mapping in human disease. Science. 2008; 322(5903):881-8. PMC: 2694957. DOI: 10.1126/science.1156409. View

Ogden C, Carroll M, Curtin L, McDowell M, Tabak C, Flegal K . Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006; 295(13):1549-55. DOI: 10.1001/jama.295.13.1549. View

Walley A, Asher J, Froguel P . The genetic contribution to non-syndromic human obesity. Nat Rev Genet. 2009; 10(7):431-42. DOI: 10.1038/nrg2594. View

Rebuffe-Scrive M, Surwit R, Feinglos M, Kuhn C, Rodin J . Regional fat distribution and metabolism in a new mouse model (C57BL/6J) of non-insulin-dependent diabetes mellitus. Metabolism. 1993; 42(11):1405-9. DOI: 10.1016/0026-0495(93)90190-y. View

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J . Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372(6505):425-32. DOI: 10.1038/372425a0. View

Wang Y, Beydoun M, Liang L, Caballero B, Kumanyika S . Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring). 2008; 16(10):2323-30. DOI: 10.1038/oby.2008.351. View

Morris K, Ishikawa A, Keightley P . Quantitative trait loci for growth traits in C57BL/6J x DBA/2J mice. Mamm Genome. 1999; 10(3):225-8. DOI: 10.1007/s003359900977. View

10.

Manolio T, Collins F, Cox N, Goldstein D, Hindorff L, Hunter D . Finding the missing heritability of complex diseases. Nature. 2009; 461(7265):747-53. PMC: 2831613. DOI: 10.1038/nature08494. View

11.

Matin A, Collin G, Asada Y, Varnum D, Nadeau J . Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain. Nat Genet. 1999; 23(2):237-40. DOI: 10.1038/13874. View

12.

Vogel H, Nestler M, Ruschendorf F, Block M, Tischer S, Kluge R . Characterization of Nob3, a major quantitative trait locus for obesity and hyperglycemia on mouse chromosome 1. Physiol Genomics. 2009; 38(2):226-32. PMC: 2712221. DOI: 10.1152/physiolgenomics.00011.2009. View

13.

Hinney A, Nguyen T, Scherag A, Friedel S, Bronner G, Muller T . Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS One. 2007; 2(12):e1361. PMC: 2137937. DOI: 10.1371/journal.pone.0001361. View

14.

Castro A, Zambrano N, Kaune H, Madariaga M, Lopez P, Mericq V . YqTER deletion causes arrest of spermatogenesis in early puberty. J Pediatr Endocrinol Metab. 2005; 17(12):1675-8. DOI: 10.1515/jpem.2004.17.12.1675. View

15.

Nadeau J, Singer J, Matin A, Lander E . Analysing complex genetic traits with chromosome substitution strains. Nat Genet. 2000; 24(3):221-5. DOI: 10.1038/73427. View

16.

Maes H, Neale M, Eaves L . Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997; 27(4):325-51. DOI: 10.1023/a:1025635913927. View

17.

Belknap J . Chromosome substitution strains: some quantitative considerations for genome scans and fine mapping. Mamm Genome. 2004; 14(11):723-32. DOI: 10.1007/s00335-003-2264-1. View

18.

Buchner D, Burrage L, Hill A, Yazbek S, OBrien W, Croniger C . Resistance to diet-induced obesity in mice with a single substituted chromosome. Physiol Genomics. 2008; 35(1):116-22. PMC: 2536825. DOI: 10.1152/physiolgenomics.00033.2008. View

19.

Malek R, Wang H, Kwitek A, Greene A, Bhagabati N, Borchardt G . Physiogenomic resources for rat models of heart, lung and blood disorders. Nat Genet. 2006; 38(2):234-9. DOI: 10.1038/ng1693. View

20.

Wuschke S, Dahm S, Schmidt C, Joost H, Al-Hasani H . A meta-analysis of quantitative trait loci associated with body weight and adiposity in mice. Int J Obes (Lond). 2006; 31(5):829-41. DOI: 10.1038/sj.ijo.0803473. View