Related Experiment Video
Updated: Aug 20, 2026

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Allelic differences in a quantitative trait locus affecting insulin-like growth factor-I impact skeletal acquisition
Clifford J Rosen1, Cheryl Ackert-Bicknell, Wesley G Beamer
1The Jackson Laboratory, Bar Harbor, Maine, USA.
Abstract:
Insulin-like growth factor-I (IGF-I) is critical for optimal skeletal growth and maintenance. Knockout and transgenic models have provided significant insights into the role of IGF-I in bone modeling and remodeling. Congenic mice demonstrate allelic differences in particular quantitative trait loci (QTL). One such model is congenic 6T, which contains a QTL for reduced serum IGF-I donated from C3H/HeJ on a pure C57Bl/6 J (B6) background. In this study we found a 30%-50% reduction in IGF-I expression in bone, liver, and fat of the congenic 6T mouse, as well as lower circulating IGF-I compared with control B6. 6T mice also had a greater percentage body fat, but reduced serum leptin. These changes were associated with reduced cortical and trabecular bone mineral density, impaired bone formation but no change in bone resorption. Moreover, the anabolic skeletal response to intermittent parathyroid hormone (PTH) therapy was blunted in 6T compared with B6, potentially in response to greater programmed cell death in osteocytes and osteoblasts of 6T. In summary, allelic differences in IGF-I expression impact peak bone acquisition and body composition, as well as the skeletal response to PTH. Lifelong changes in circulating and skeletal IGF-I may be relevant for the pathophysiology of several diseases, including chronic renal failure.
Related Concept Videos
Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Polygenic Traits
Nature and Nurture
Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Insulin: The Receptor and Signaling Pathways
