Basic Research

BASIC RESEARCH IN THE JEPSEN LABORATORY

Basic research in the Jepsen Laboratory is done primarily on mice. There are many different strains used in the lab, depending on the research question. All animal use in the lab is governed by the Institutional Animal Care and Use Committee (IACUC).

Recombinant Inbred and Chromosome Substitution mouse strains are used to study how functional interactions among traits mature during growth and how this process defines adult bone stiffness, strength, and toughness.

PROTOCOLS

Recently, many of the protocols the Jepsen Laboratory uses for basic research were assembled for Current Protocols in Mouse Biology. (Clicking on links below will open the protocol .pdf file in a new window)

General bone preparation protocols

• Bone harvesting protocol
• Bone ashing protocol

NanoCT protocols. These protocols are designed for a GE nanoTom S system. If you have a different microCT or nanoCT system, you will need to adjust the protocol.

• Protocol for scanning adult mouse femurs
• Protocol for scanning adult mouse lumbar vertebrae
• Protocol for scanning developing mouse femurs (Will be uploaded soon, please check back)
• Protocol for scanning developing mouse lumabr vertebrae (Will be uploaded soon, please check back)

Mechanical testing protocols. These protocols were written for use with a custom testing frame used on an MTS mini-bionix system.

• Mouse 4 point bending protocol
• Mouse vertebral compression testing (Will be uploaded soon, please check back)

Other protocols

• RNA Homogenization
• RNA Extraction for Bone
• Western Blot Buffers
• SOST Immunohistochemistry
• CD31 Immunohistochemistry
• Immunohistochemistry Buffers
• Protein Extraction for Bone
• Protein Quantification Using BCA Assay

SELECTED PUBLICATIONS

1. Bonadio J, Jepsen KJ, Mansoura MK, Jaenisch R, Kuhn JL, and Goldstein SA. A murine skeletal adaptation that significantly increases cortical bone mechanical properties - Implications for human skeletal fragility. Journal of Clinical Investigation, 92:1697-1705, 1993.
2. Jepsen KJ, Goldstein SA, Kuhn JL, Schaffler MB, Bonadio J. Type I collagen mutation compromises the post-yield behavior of Mov13 long bone. Journal of Orthopaedic Research, 14:493-499, 1996.
3. Jepsen KJ, Schaffler MB, Kuhn JL, Goulet RG, Bonadio J, Goldstein SA. Type I collagen mutation alters the strength and fatigue behavior of Mov13 cortical tissue. Journal of Biomechanics, 30(11/12):1141-1147, 1997.
4. Jepsen, K.J., Pennington, D.E., Lee, Y.-L., Warman, M., Nadeau, J. Bone brittleness varies with genetic background in A/J and C57BL/6J inbred mice. J Bone Miner Res, 16(10):1854-1862, 2001.
5. Jepsen KJ, Akkus O, Majeska RJ, Nadeau JH. Hierarchical relationship between genetically determined bone traits and whole bone mechanical properties in inbred mice. Mammalian Genome, 14(2):97-104, 2003.
6. Tommasini SM, Morgan TG, van der Meulen MCH, Jepsen KJ. Genetic variation in structure-function relationships for the inbred mouse lumbar vertebral body. Journal of Bone and Mineral Research, 20(5):817-827, 2005.
7. Price C, Herman BC, Lufkin T, Goldman HM, Jepsen KJ. Genetic variation in bone growth patterns defines adult mouse bone fragility. Journal of Bone and Mineral Research, 20(11): 1983-1991, 2005.
8. Jepsen KJ, Hu B, Tommasini SM, Courtland H-W, Price C, Terranova CJ, Nadeau JH. Genetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragility. Mammalian Genome, 18(6-7):492-507, 2007. PMC1998883
9. Tommasini SM, Wearne SL, Hof PR, Jepsen KJ. Percolation theory relates corticocancellous architecture to mechanical function in vertebrae of inbred mouse strains. Bone; 42(4), 2008. PMC2650241
10. Courtland H-W, Nasser P, Goldstone AB, Spevak L, Boskey AL, Jepsen KJ. FTIRI microspectroscopy and micromechanical testing reveal intra-species variation in mouse bone mineral composition and matrix maturity. Calcified Tissue International, 83(5):342-353, 2008. PMC2650490
11. Tommasini SM, Hu B, Nadeau JH, Jepsen KJ. Phenotypic integration among trabecular and cortical bone traits establishes mechanical functionality of inbred mouse vertebrae. J Bone Miner Res, 24:606-620, 2009. PMC2659510
12. Jepsen KJ, Hu B, Tommasini SM, Courtland H-W, Price C, Cordova M, Nadeau JH. Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strains. Mammalian Genome, 20(1):21-33, 2009. PMC2650248
13. Jepsen KJ, Courtland H-W, Nadeau JH. Genetically-determined phenotype covariation networks control bone strength. J Bone Miner Res, 25:1581-1593, 2010. PMID 20200935 (PMC3153133)
14. Smith, L., Bigelow, E. M., Jepsen, K. J. Systematic evaluation of skeletal mechanical function. Current protocols in mouse biology, 39-67, 2013.
15. Smith, L. M., Bigelow, E. M., Nolan, B. T., Faillace, M. E., Nadeau, J. H., Jepsen, K. J. Genetic perturbations that impair functional trait interactions lead to reduced bone strength and increased fragility in mice. Bone, 67, 130-138, 2014.
16. Schlecht SH, Smith LM, Ramcharan MA, Bigelow EMR, Nolan BT, Mathis NJ, Cathey A, Manley Jr E, Nadeau JH, Jepsen KJ. Canalization leads to similar whole bone mechanical function at maturity in two inbred strains of mice, J Bone Miner Res, in press, 2017. PMID (28177139) (PMC5133411)
17. Ramcharan MA, Faillace ME, Guengerich Z, Williams VA, Jepsen KJ, The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body. Osteoporosis Int, 28(3):1133-1143. PMID 27734101
18. Xin F, Smith LM, Susiarjo M, Bartolomei MS, Jepsen KJ: Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system. Environ Epigenet 4(2): dvy002, 2018. PM29732168/PMC5920333

LINKS FOR MORE INFORMATION

• Jackson Labs Mouse Phenome Project
• IACUC