Abstract
Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL.
Highlights
The rationale for this project was born from challenges in mapping obesity genes
C57BL/6ByJ (B6) and 129P3/J (129) inbred mice were purchased from the Jackson Laboratory (Bar Harbor, ME) and used as founders of consomic mice and parents of inbred mice used for body composition analyses
Five the QTLs were named in the original manuscript and those are the names we use in this report, i.e., Bwq5-6 and Bdln3-5
Summary
Occurring mutations in a single gene are sufficient to radically alter body size, body length, and obesity [1, 2]. These are rare in humans and not relevant to milder and more common forms of obesity. Another method to investigate the genetic substrates of obesity is through the systematic study of knockout mouse strains. Surveys of these genetically engineered mice indicate that up to one-third of viable knockout mouse strains.
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