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Physiol. Genomics (July 15, 2003). doi:10.1152/physiolgenomics.00063.2003
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Submitted on April 14, 2003
Accepted on July 13, 2003

Quantitative Trait Loci for Insulin-like Growth Factor-I, Leptin, Thyroxine, and Corticosterone in Genetically Heterogeneous Mice

James M Harper1*, Andrzej T Galecki2, David T Burke3, Stephen L Pinkosky4, and Richard A Miller5

1 Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Institute of Gerontology, University of Michigan, Ann Arbor, MI, USA
2 Geriatrics Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Institute of Gerontology, University of Michigan, Ann Arbor, MI, USA; DVA Medical Center, Ann Arbor, MI, USA
3 Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI, USA
4 Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA
5 Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Geriatrics Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; DVA Medical Center, Ann Arbor, MI, USA

* To whom correspondence should be addressed. E-mail: millerr{at}umich.edu.

Genotype information was collected at 87 loci in a group of 1108 UM-HET3 mice bred as the progeny of [BALB/cJ x C57BL/6J]F1 mothers and [C3H/HeJ x DBA/2J]F1 fathers, for which T4, IGF-I, and leptin levels had been measured at 4 and 15 months of age. The data provided significant evidence for quantitative trait loci (QTL) modulating IGF-I levels on chromosomes 1, 3, 8, 10, and 17; for loci affecting T4 on chromosomes 4, 15, and 17; and for leptin on chromosome 3. Fecal levels of corticosterone at 17 months of age were influenced by a QTL on chromosome 1. Nine other gene/hormone associations reached a nominal p < 0.01, providing suggestive but not statistical evidence for additional QTL. QTL with an influence on a given hormone were in nearly all cases additive, with little or no evidence for epistasis. Of the 12 strongest QTL, 5 had effects that were age-dependent, having more effect in 15-month old than in 4-month old mice in all but one case; the other QTL had effects that were apparently age-independent. These results show that the genetic controls over late-life hormone levels are complex, and dependent on effects of genes that act both early and late in the life course.




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