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Genome‐wide search for loci controlling serum IGF binding protein levels of mice
Author(s) -
Brockmann Gudrun A.,
Haley Chris S.,
Wolf Eckhard,
Karle Steffanie,
Kratzsch Juergen,
Renne Ulla,
Schwerin Manfred,
Hoeflich Andreas
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fsb2fj000391com
Subject(s) - biology , quantitative trait locus , locus (genetics) , genetics , genetic linkage , hyperinsulinemia , gene , chromosome , insulin like growth factor binding protein , endocrinology , obesity , insulin like growth factor , growth factor , insulin resistance , receptor
A segregating F 2 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 ( Igtfbp3q1; 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. FASEB J. 15, 978–987 (2001)