Quantitative trait loci that control body weight in DDD/Sgn and C57BL/6J inbred mice

Abstract

Inbred DDD/Sgn mice are heavier than inbred C57BL/6J mice. In the present study, we performed quantitative trait loci (QTL) mapping for body weight using R/qtl in reciprocal F male populations between the two strains. We identified four significant QTL on Chrs 1, 2, 5, and 17 (proximal region). The DDD/Sgn allele was associated with increased body weight at QTL on Chrs 1 and 5, and the DDD/Sgn allele was associated with decreased body weight at QTL on Chrs 2 and 17. A multiple regression analysis indicated that the detected QTL explain 30.94 % of the body weight variation. Because DDD/Sgn male mice have extremely high levels of circulating testosterone relative to other inbred mouse strains, we performed QTL mapping for plasma testosterone level to examine the effect of testosterone levels on body weight. We identified one suggestive QTL on Chr 5, which overlapped with body weight QTL. The DDD/Sgn allele was associated with increased testosterone level. Thus, we confirmed that there was a genetic basis for the changes in body weight and testosterone levels in male mice. These findings provide insights into the genetic mechanism by which body weight is controlled in male mice.

Identification of Quantitative Trait Loci That Determine Plasma Total-Cholesterol and Triglyceride Concentrations in DDD/Sgn and C57BL/6J Inbred Mice

“…We previously performed QTL mapping for body weight in the same F 2 intercross population and identified four significant QTL on Chrs 1, 2, 5, and 17 [11]. Of these QTL, those on Chrs 1 and 5 coincided with QTL for CHO and TG concentrations, and that on Chr 17 coincided with QTL for CHO concentration on the basis of chromosomal localization (Table 2).…”

“…Reciprocal crosses between DDD and B6 strains produced DB (♀DDD ×  ♂B6) F 1 and BD (♀B6 ×  ♂DDD) F 1 mice, both of which were intercrossed to produce DB F 2 ( n = 150) and BD F 2 ( n = 150) male mice [11]. …”

Effects of quantitative trait loci determining testicular weight in DDD/Sgn inbred mice are strongly influenced by circulating testosterone levels

“…The plasma testosterone level was determined in parental, F 1 and F 2 mice, as previously described [12]. The paired testes were weighed on an electric balance to the nearest milligram.…”

“…In addition to heavy testes, DDD males are known to have very high blood testosterone level [11,12]. Indeed, while the average plasma testosterone level in B6 males was 0.49±0.18 ng/mL, that in DDD males was 13.07±3.12 ng/mL [12]. Testicular growth and development is strongly influenced by androgen [13,14].…”

“…Although both testis weight and plasma testosterone level are inherited traits, interrelationship between them is not fully established. We have previously performed QTL mapping for plasma testosterone level in F 2 male mice between DDD and B6 [12] but did not detect any significant QTL. Even though the genetic basis of plasma testosterone level in DDD mice is unclear, we hypothesize that high blood testosterone level influence extremely heavy testes in DDD mice.…”