Genomics 2 !!

Diet effects on weight gain and body composition in high growth (hg/hg) mice


A LARGE NUMBER OF GROWTH DISORDERS in humans have been classified as overgrowth syndromes . Many of these syndromes have genetic origins and may lead to hormonal imbalances that affect growth patterns under different nutritional environments. A typical example is the effect of an increased energy intake leading to obesity in children, as well as an increase in height relative to leaner children . The underlying mechanisms of nutrition and linear growth are central to understanding the etiology of many of the interactions leading to overgrowth.

The genetics of growth has extensively used the laboratory mouse as a model of study. However, the majority of mouse mutations affecting growth result in a reduction in body size . Increased size mutants have largely been those associated with obesity . More recently, some mouse knockouts with increased size have been described, but they have specific tissue abnormalities or endocrine dysfunction. In contrast to these models, one natural mutation in the mouse, high growth (hg) , has a generalized increase in body size and is not obese . Therefore, it constitutes a valuable model with which to study genetic and nutritional aspects of overgrowth.
The hg locus is a partially recessive mutation that dramatically enhances postweaning weight gain and adult body size. Genetic analysis of the mutation has determined that the hg locus is a 500-kb deletion in mouse chromosome 10 . The identification and characterization of genes within the hg deletion are in progress, and a positional candidate gene has been identified . However, the causality of this particular phenotype is not yet fully understood. Mice homozygous for the deletion show an increased growth rate of up to 50% accompanied by a higher energetic efficiency and/or lower maintenance requirements . The effects of the mutation are detected early in development, manifested by delayed muscular cell fusion and an increase in muscle fiber number . Interestingly, high growth mice have lower concentrations of growth hormone (GH) but much higher concentrations of insulin-like growth factor I (IGF-I) in plasma than do normal mice . Despite substantial changes in growth rate and size, the mice are proportional in the size of body components .

Nutrition is the most important nongenetic factor affecting growth and body composition traits in mammals . Moreover, complex interactions between genotype and diet composition have been detected in experiments evaluating growth in mice . Therefore, the goal of this study was to assess the importance of genotype x diet interactions on the effects of a major locus regulating animal growth. High growth and control mice were fed diets varying in protein and energy content from 3 to 12 wk of age. To describe the effects of hg on important physiological processes related to growth, we measured weight gain, feed intake, body composition and the concentrations of insulin, leptin, IGF-I, and glucose.