Quantitative trait locus mapping of genes that control body length and plasma insulin-like growth factor 1 level in mice

Jun-Ichi Suto

doi:10.1186/1756-0500-5-547

Abstract

BackgroundThe Ay allele at the agouti locus causes obesity and promotes linear growth in mice. The effect of the Ay allele on obesity has been extensively investigated, whereas its effect on body length is only poorly analyzed. To gain insight into the genetic control of body length, quantitative trait locus (QTL) analysis was performed in F2 female mice produced by crossing C57BL/6 J females and DDD.Cg-Ay males. A congenic DDD.Cg-Ay strain was established by introgressing the Ay allele from the B6.Cg-Ay strain by backcrossing for 12 generations. DDD.Cg-Ay females were longer than B6.Cg-Ay females; therefore, QTLs that interact with the Ay allele may be identified for body length. In addition, QTL analysis was also performed for plasma insulin-like growth factor 1 (IGF1) levels because IGF1 is known to play essential roles in growth and development. If QTLs for IGF1 levels coincide with those for body length, we can gain endocrinological insight into the QTLs for body length.ResultsCorrelations between body length and IGF1 levels were statistically significant in F2 populations. For body length, two significant QTLs were identified on chromosomes 15 and 17. For IGF1 levels, three significant QTLs were identified on chromosomes 10, 12, and 19. QTLs on chromosomes 12 and 19 appeared to be novel, and the latter interacted with the Ay allele.ConclusionQTLs for body length and IGF1 levels contained candidate genes that were components of the growth hormone/insulin-like growth factor axis. However, there was no overlap between QTLs for these two traits. Contrary to our expectations, QTLs that interacted with the Ay allele were identified not for body length but for IGF1 levels. Body length and IGF1 levels were, thus, controlled by different sets of genes.

Highlights

The Ay allele at the agouti locus causes obesity and promotes linear growth in mice
In Ay mice, the Ay allele is associated with a large deletion, causing agouti gene expression to be aberrantly controlled by the unrelated Raly gene promoter and leading to its ectopic overexpression [4,7,8,9]
We developed a novel strain congenic for the Ay allele in an inbred DDD/Sgn strain background, i.e., DDD.Cg-Ay strain [13]

Summary

Introduction

The Ay allele at the agouti locus causes obesity and promotes linear growth in mice. To gain insight into the genetic control of body length, quantitative trait locus (QTL) analysis was performed in F2 female mice produced by crossing C57BL/6 J females and DDD.Cg-Ay males. DDD.Cg-Ay females were longer than B6.Cg-Ay females; QTLs that interact with the Ay allele may be identified for body length. The Ay allele is known to cause obesity and to promote linear growth [2]. In Ay mice, the Ay allele is associated with a large deletion, causing agouti gene expression to be aberrantly controlled by the unrelated Raly gene promoter and leading to its ectopic overexpression [4,7,8,9]. We developed a novel strain congenic for the Ay allele in an inbred DDD/Sgn (hereafter DDD) strain background, i.e., DDD.Cg-Ay (hereafter DDD-Ay) strain [13]

Methods

Results

Discussion

Conclusion