Information - Concepts In Nutrigenomics - Model Systems

Mice, Yeast, Fruit flies, Worms

Determining how nutrition affects health and the development of chronic diseases has proved challenging because humans are not good experimental subjects for most molecular genetic studies: each human has a unique genotype and it is difficult to control for environmental influences. In contrast, both of these variables can be controlled in studies with laboratory animals. Rats and mice are particularly useful for such studies because of the relatively short generation times and planned breeding can be done to test genetic hypotheses. The human and mouse genome projects demonstrate the relatedness of the two species and comparative genomic methods are being used to understand observed differences in physiology.

Nutritionists have long used outbred or individual inbred strains of rats and mice for analyzing the effects of diet on health, (equivalent to studying, respectively, populations or individuals). Many nutritionists and geneticists are developing best practices for controlling genetic backgrounds, nutrient intakes by using defined diets, and nutritional status by timing eating during the experimental procedures.

Mice of defined genotype are important for identifying gene-nutrient interactions, gene-gene interactions (epistasis), and regulation by epigenetics - the heritable changes in gene function that occur without a change in the sequence of nuclear DNA.

In addition to studying basic molecular, nutritional, and genetic processes, inbred mouse strains often have differences in disease susceptibilities that are similar to those observed between individual humans. Altering the highly controlled environmental conditions, including diets, changes the regulation of genes that produce disease in susceptible mice but not in mice that are more resistant to the disease. Comparative genomic methods, therefore, are effective for understanding differences between species (e.g., mouse to human) but also offer the possibility of identifying genes responsible for susceptibility to chronic diseases, how they interact with each other, and with environmental factors.

In addition to laboratory animals, nutrigenomics research is conducted in yeast (Saccharomyces cerevisiae), fruit flies (Drosophila sp.), and worms (Caenorhabditis elegans).

Photo of obese yellow, agouti, and pseudoagouti mice courtesy of George Wolff.

Further reading

Chiu, S, Diament, AL, Fisler, JS, and Warden, CH. 2006. Gene-Gene Epistasis and Gene-Environment Interactions Influence Diabetes and Obesity. In Nutritional Genomics: Discovering the Path to Personalized Nutrition.  Kaput, J and Rodriguz, R (eds). Wiley and Sons, Inc. NY. 2006. pp. 135 - 151.

Hartman IV, JL.  2006. Genetic and Molecular Buffering of Phenotypes. In Nutritional Genomics: Discovering the Path to Personalized Nutrition.  Kaput, J and Rodriguz, R (eds). Wiley and Sons, Inc. NY. 2006. pp. 103 - 133.

Kaput, J, Klein, KG, Reyes, EJ, Kibbe, WA, Visek, WJ, and Wolff, G.  2004.  Identification of Genes Contributing to the Obese Yellow Avy phenotype:  Caloric Restriction, Genotype, Diet x Genotype Interactions. Physiological Genomics 18, 316-324. PMID: 15206695 

Kaput, J.  An Introduction and Overview of Nutritional Genomics:  Application to Type 2 Diabetes and International Genomics. In Nutritional Genomics: Discovering the Path to Personalized Nutrition.  Kaput, J and Rodriguz, R (eds). Wiley and Sons, Inc. NY. 2006. pp. 1 - 35.

Lin, SJ.  Molecular Mechanisms of Longevity Regulation and Calorie Restriction.  In Nutritional Genomics: Discovering the Path to Personalized Nutrition.  Kaput, J and Rodriguz, R (eds). Wiley and Sons, Inc. NY. 2006. pp. 207 - 218.