Originally published as Genetics Published Articles Ahead of Print on May 15, 2006.

Genetics, Vol. 173, 2143-2149, August 2006, Copyright © 2006
doi:10.1534/genetics.105.053983

Functional Implication of an Arg307Gly Substitution in Corticosteroid-Binding Globulin, a Candidate Gene for a Quantitative Trait Locus Associated With Cortisol Variability and Obesity in Pig

* Laboratoire de Neurogénétique et Stress, INRA UMR1243—Université Victor Ségalen Bordeaux 2, 33077 Bordeaux, France and {dagger} PIC, Oxfordshire, OX13 5FE, United Kingdom

1 Corresponding author: Institut François Magendie, Université Bordeaux 2, 146 rue Leo Saignat, 33077 Bordeaux Cedex, France.
E-mail: mpmoisan{at}bordeaux.inra.fr

We previously reported that corticosteroid-binding globulin gene (Cbg) may be the causal gene of a quantitative trait locus associated with cortisol levels, fat deposition, and muscle content in a pig intercross. Sequence analysis of parental animals allowed us to identify four amino-acid substitutions. Here we have examined if any of these single amino acid substitutions could be responsible for the difference in CBG binding and affinity for cortisol between the parental breeds, using in vitro assays of Cbg variants after transfection of mammalian cells. Additionally, the Cbg coding region was analyzed in samples from a synthetic pig line to study association between polymorphism and CBG biochemical properties, carcass composition, and meat quality. Both in vitro transfection assays and the association studies suggest a role of the Arg307Gly mutation in increasing CBG capacity (by >70%) and decreasing CBG affinity for cortisol (by 30%). The Ile265Val substitution may also have an effect on decreasing CBG affinity for cortisol by 25%. The mutations Ser15Ile and Thr257Met do not seem to have an effect on CBG parameters. The Arg307Gly substitution was the only mutation associated with a parameter of meat quality and no mutation was linked to carcass composition.




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