Experiment
The C57BL/6J-ChrA/J/NaJ (B6.A) panel of chromosome substutution strains (CSSs) is a unique model for studying resistence to diet induced obesity. C57BL/6J male mice are significantly more susceptible than A/J males to diet induced obesity. In the present study 20 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 (QTL) on individual chromosomes.
CSS females were crossed with C57BL/B6 (B6) males), F1 offspring were then intercrossed to generate F2 male progeny, 75-93 per CSS cross. QTL analysis on the intercosses between each CSS strain (except CSS-Y and CSS-Mito) and the B6 host strain revealed significant QTL on Chromosomes 1, 6, 10, 11, and 13. The analysis was performed testing for QTL that affected:
IW, weight in grams at app 35 days of age;
MW, weight in grams at app 90 days of age;
FW, weight in grams at app 135 days of age;
BMI, FW in grams / final nasonanal length in cms;
EWG, mean weight gain per day in grams/day for app first 55 days;
FWG, mean weight gain per day in grams per day for second app 45 days;
WG, mean weight gain per day in grams/per day.
On Chromosome 13 (C57BL/6J-Chr 13A/J/NaJ x C57BL/6J) the following significant QTL was identified:
Obrq7 (obesity resistance QTL 7) mapped to Chr 13 at 24 cM in a 1.5 LOD support interval between 12-31 cM with a LOD=4.87, p=0.042 for trait MW.
The following suggestive QTL were also identified on Chr 13:
at 38 cM, spanning 8-53 cM, LOD=4.13, p=0.15, affecting trait FW;
at 15 cM, spanning 0-51 cM, LOD=3.26, p=0.53, affecting trait BMI;
at 23 cM, spanning 0-47 cM, LOD=3.39, p=0.45, influencing trait WG; and
at 35 cM, spanning 6-51 cM, LOD=3.24, p=0.54, influencing trait FWG.
[Table 2 and Sup Table 5].
QTL analysis was performed using 94 (C57BL/6J x A/J) intercross progeny to test whether QTL detected in the CSS were comparable to those detected using a traditional intercross between the parental strains.
No significant QTL were detected in the parental strain intercross. However, suggestive QTL were identified on Chr 13 and 17 for IW. On Chr 13 the suggestive QTL mapped to 53 cM, p=0.495, with a 1.5 LOD support interval between 34 and 74 cM. On Chr 17 the QTL mapped to 17 cM, p=0.526, with a 1.5 LOD support interval between 0 and 48 cM. Interestingly neither of these QTL were detected in the CSS intercross analysis. [Sup Table 7].