QTL for body composition on chromosome 7 detected using a chromosome substitution mouse strain

Abstract

Objective: Previous studies in mice have detected quantitative trait loci (QTLs) on chromosome 7 that affect body composition. As a step toward identifying the responsible genes, we compared a chromosome 7 substitution strain C57BL/6J-Chr7(129S1/SvImJ)/Na (CSS-7) to its host (C57BL/6J) strain.

Methods and procedures: Fourteen-week-old mice were measured for body size (weight, length), organ weight (brain, heart, liver, kidneys, and spleen), body and bone composition (fat and lean weight; bone area, mineral content, and density), and individual adipose depot weights (gonadal, retroperitoneal, mesenteric, inguinal, and subscapular). Differences between the CSS-7 strain and the host strain were interpreted as evidence for the presence of one or more QTLs on chromosome 7.

Results: Using this criterion, we detected QTLs for body weight, bone area, bone mineral content, brain, and heart weight, most adipose depot weights and some indices of fatness. A few strain differences were more pronounced in males (e.g., most adiposity measures) and others were more pronounced in females (e.g., bone area). QTLs for body length, lean weight, bone mineral density, and kidney, spleen, and liver weight were not detected.

Discussion: This study found several associations that suggest one or more QTLs specific to the weight of select tissues and organs exist on mouse chromosome 7. Because these loci are detectable on a fixed and uniform genetic background, they are reasonable targets for high-resolution mapping and gene identification using a congenic approach.

Figure 1

(a) Chromosome composition of a chromosome substitution (consomic) strain (CSS-7). (b) Hypothetical patterns of trait values by strain and the interpretation of quantitative trait loci (QTLs) results: (1) The mean trait values of the host and CSS-7 strains do not differ (no QTLs are detected). (3) The CSS-7 has a lower trait value than the host strain (a minus QTL is detected).

Figure 2

Body composition, adipose depot and organ weights by strain and sex. Data are means ± s.e.m. The asterisk denotes sex-specific and sex-dependent quantitative trait loci (QTLs) effects. Fat weight was determined in two ways, by necropsy (dissection) and by DEXA. Fat weight was expressed as a ratio by dividing by body weight (BW) or body length (cm) × 100. BMC, bone mineral content (mg); BMD, bone mineral density (mg/cm²); BMI, body mass index (g/cm²) × 100; DEXA, dual-energy X-ray absorptiometry.