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Genome-wide search for loci controlling serum IGF binding protein levels of mice

GUDRUN A. BROCKMANN^*1, CHRIS S. HALEY, ECKHARD WOLF, STEFFANIE KARLE^*, JUERGEN KRATZSCH, ULLA RENNE^*, MANFRED SCHWERIN^* and ANDREAS HOEFLICH

^* Research Institute for the Biology of Farm Animals, 18196 Dummerstorf, Germany;
Roslin Institute (Edinburgh), Roslin, Midlothian EH25 9PS, U. K.;
Department of Molecular Animal Breeding, Ludwig-Maximilian University, 81377 Munich, Germany; and
Departments of Clinical Chemistry and Pathobiochemistry, University of Leipzig, 04103 Leipzig, Germany

¹Correspondence: Department of Molecular Biology, Research Institute for the Biology of Farm Animals, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany. E-mail: Gudrun.Brockmann{at}fbn-dummerstorf.de

A segregating F₂ pedigree based on two mouse lines (DU6i and DBA/2) with extremely different growth characteristics was generated to search for loci affecting serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) and to estimate their effects on growth and body composition. DU6i is characterized by high body mass and obesity associated with hyperinsulinemia, hyperleptinemia, and elevated serum IGF-I concentrations. Furthermore, significantly elevated serum levels of IGFBP-2, IGFBP-3, and IGFBP-4 were found in DU6i vs. DBA/2 mice. Linkage analysis identified loci with major effects on the serum level of IGFBP-3 on Chromosome 5 at 58 cM (Igfbp3q1; F = 9.9) and on Chromosome 10 at 46 cM (Igfbp3q2; F = 33.8). A locus significantly influencing serum IGFBP-2 levels in males was found on Chromosome 7. Additional linkage was detected in males and females for IGFBP-2 on Chromosomes 8, 11, 14, 17, and X, and for IGFBP-4 on Chromosome 4. Additional loci affecting IGFBPs acted in a sex-specific manner. The identified loci coincide in part with chromosomal regions controlling growth and obesity. Thus, multiple genes or pleiotropic gene effects may be assumed for these chromosomal regions. The identification of quantitative trait loci for IGFBPs as subcomponents of growth regulation and differentiation will further improve the understanding of complex trait regulation.—Brockmann, G. A., Haley, C. S., Wolf, E., Karle, S., Kratzsch, J., Renne, U., Schwerin, M., Hoeflich, A. Genome-wide search for loci controlling serum IGF binding protein levels of mice.

Key Words: IGFBP-2 • IGFBP-3 • IGFBP-4 • linkage

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