Genomic Mapping of Direct and Correlated Responses to Long-Term Selection for Rapid Growth Rate in Mice

Abstract

Understanding the genetic architecture of traits such as growth, body composition, and energy balance has become a primary focus for biomedical and agricultural research. The objective of this study was to map QTL in a large F 2 (n ϭ 1181) population resulting from an intercross between the M16 and ICR lines of mice. The M16 line, developed by long-term selection for 3-to 6-week weight gain, is larger, heavier, fatter, hyperphagic, and diabetic relative to its randomly selected control line of ICR origin. The F 2 population was phenotyped for growth and energy intake at weekly intervals from 4 to 8 weeks of age and for body composition and plasma levels of insulin, leptin, TNF␣, IL6, and glucose at 8 weeks and was genotyped for 80 microsatellite markers. Since the F 2 was a cross between a selection line and its unselected control, the QTL identified likely represent genes that contributed to direct and correlated responses to longterm selection for rapid growth rate. Across all traits measured, 95 QTL were identified, likely representing 19 unique regions on 13 chromosomes. Four chromosomes (2, 6, 11, and 17) harbored loci contributing disproportionately to selection response. Several QTL demonstrating differential regulation of regional adipose deposition and age-dependent regulation of growth and energy consumption were identified.

Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice

“…A series of QTL related to body weight, food intake, energy balance and other metabolic parameters map to Chr 4 and 11 in the exact same regions as the CARTta QTL (Bevova et al, 2006;Moody et al, 1999;Plum et al, 2000;Ueda et al, 1999;Allan et al, 2005;Rocha et al, 2004).…”

Quantitative Trait Loci that Control Body Weight and Obesity in an F2 Intercross between C57BL/6J and DDD.Cg-Ay Mice

“…In contrast to the proximal locus, only a few coincidental QTLs have been reported for the locus on distal chromosome 17. Allan et al [1] analyzed growth and body composition in a large F 2 population resulting from an intercross between M16 and ICR and identified several QTLs for body weight, growth, and fat-ness. The M16 line is more obese than ICR, and the M16 allele is associated with increases in these trait values, in a way similar to Bwdq5 and Obdq4.…”

QTL Mapping of Genes Controlling Plasma Insulin and Leptin Concentrations: Metabolic Effect of Obesity QTLs Identified in an F₂ Intercross between C57BL/6J and DDD.Cg-<i>A^y</i> Inbred Mice

“…Mlepq2, identified in an F 2 intercross between M16 and ICR strains [1], coincided with Lepdq1 on distal chromosome 17. In accordance with the effect of Lepdq1 on obesity, Mlepq2 also colocalized with a QTL accounting for growth and the amount of body fat in that cross.…”