Genetic Effects for Femoral Biomechanics, Structure, and Density in C57BL/6J and C3H/HeJ Inbred Mouse Strains

Daniel L. Koller, Jennifer Schriefer, Qiwei Sun, Kathryn L. Shultz, Leah R. Donahue, Clifford J. Rosen, Tatiana Foroud, Wesley G. Beamer, Charles H. Turner

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Genome-wide QTL analysis for bone density, structure, and biomechanical phenotypes was performed in 999 (B6xC3H)F2 mice. Multivariate phenotypes were also derived to test for pleiotropic QTL effects. Highly significant QTLs were detected with pleiotropic effects on many of these phenotypes, and QTLs with unique effects on specific phenotypes were found as well. Introduction: The inbred C57BL/6J (B6) and C3H/HeJ (C3H) mouse strains were previously shown to segregate quantitative trait loci (QTLs) for femoral bone density. Materials and Methods: The 999 s filial (F2) mouse progeny were further phenotyped for measures of femoral biomechanics (load to failure, Fu; work to failure, U; stiffness, S), structure (polar moment of inertia, Ip; moment of inertia ratio, Ir), and more specific femoral midshaft bone density measures (cortical and total vBMD). Two novel multivariate phenotypes were computed using principal component analysis, thus aiding in the exploration of pleiotropic effects of the QTLs detected. Results and Conclusions: Results of a genome-wide analysis provided strong evidence of pleiotropic QTL effects on chromosome 4, with six of the seven primary phenotypic measures, representing femoral biomechanics, density, and structure, producing LOD scores greater than 8. Chromosomes 1, 8, 13, and 14 were also identified as harboring QTLs that affect phenotypes in two of the three aspects of bone properties. QTLs uniquely contributing to variability in biomechanical measures were identified on chromosomes 10 and 12, whereas a QTL solely affecting structure was found on chromosome 17. Analysis of the evidence for pleiotropic effects using principal component analysis revealed pleiotropic QTLs on chromosomes 4 and 14, influencing nearly all the bone phenotypes measured and revealed QTLs on chromosomes 1, 8, 13, and 17 with pleiotropic effects restricted to either density or the structure and stiffness phenotypes. The use of multivariate phenotypes has allowed us to identify pleiotropic effects of several QTLs previously linked in studies of other mouse strains and in human studies of bone mineral density and femoral structure, which will provide important insight regarding the importance of allelic variation on the entire skeleton.

Original languageEnglish
Pages (from-to)1758-1765
Number of pages8
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume18
Issue number10
DOIs
StatePublished - Oct 2003

Fingerprint

Inbred Strains Mice
Quantitative Trait Loci
Thigh
Biomechanical Phenomena
Phenotype
Bone Density
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 1
Principal Component Analysis
Genome
Chromosomes, Human, Pair 14
Bone and Bones
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 17
Inbred C3H Mouse
Skeleton

Keywords

  • Biomechanics
  • Bone mineral density
  • Inbred mice
  • Pleiotropy
  • Quantitative trait loci

ASJC Scopus subject areas

  • Surgery

Cite this

Genetic Effects for Femoral Biomechanics, Structure, and Density in C57BL/6J and C3H/HeJ Inbred Mouse Strains. / Koller, Daniel L.; Schriefer, Jennifer; Sun, Qiwei; Shultz, Kathryn L.; Donahue, Leah R.; Rosen, Clifford J.; Foroud, Tatiana; Beamer, Wesley G.; Turner, Charles H.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 18, No. 10, 10.2003, p. 1758-1765.

Research output: Contribution to journalArticle

Koller, Daniel L. ; Schriefer, Jennifer ; Sun, Qiwei ; Shultz, Kathryn L. ; Donahue, Leah R. ; Rosen, Clifford J. ; Foroud, Tatiana ; Beamer, Wesley G. ; Turner, Charles H. / Genetic Effects for Femoral Biomechanics, Structure, and Density in C57BL/6J and C3H/HeJ Inbred Mouse Strains. In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2003 ; Vol. 18, No. 10. pp. 1758-1765.
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AU - Sun, Qiwei

AU - Shultz, Kathryn L.

AU - Donahue, Leah R.

AU - Rosen, Clifford J.

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