Skip to main content
SpringerLink
Log in
Book cover

Osteoporosis Research pp 13–28Cite as

Skeletal Phenotyping in Rodents: Tissue Isolation and Manipulation

  • Chapter
  • First Online:

Abstract

The pioneering work of Rudolph Jaenisch at the Whitehead Institute1 and Mario Capecchi at the Howard Hughes Institute2 used modification of the mouse genome to understand the etiology and pathogenesis of human disease.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Jaenisch R. Mammalian neural crest cells participate in normal embryonic development on microinjection into post-implantation mouse embryos. Nature. 1985;318:181-183.

    Article  PubMed  CAS  Google Scholar 

  2. Thomas K, Capecchi M. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987; 51:503-512.

    Article  PubMed  CAS  Google Scholar 

  3. Fortin A, Diez E, Henderson J, Mogil J, Gros P, Skamene E. The AcB/BcA recombinant congenic strains of mice: strategies for phenotype dissection, mapping and cloning of ­quantitative trait genes. Novartis Found Symp. 2007;281: 141-153.

    Article  PubMed  CAS  Google Scholar 

  4. Rivadeneira F, Consortium GFfO. Twenty bone mineral-density loci identified by large-scal meta-analysis of genome-wide association studies. Nat Genet. 2009;41:1199-1206.

    Article  PubMed  CAS  Google Scholar 

  5. Miller P, Zapalowski C. Bone mineral density measurements. In: Goltzman D, ed. The Osteoporosis Primer. Cambridge: Cambridge University Press; 2000:262-276.

    Google Scholar 

  6. Klein R, Mitchell S, Phillips T, Belknap J, Orwoll E. Quan­titative trait loci affecting peak bone mineral density in mice. J Bone Miner Res. 1998;13:1648-1656.

    Article  PubMed  CAS  Google Scholar 

  7. Lim L, Hoeksema L, Sherin K, Committee APP. Screening for osteoporosis in the adult US population: ACPM position statement on preventative practice. Am J Prev Med. 2009;36: 366-375.

    Article  PubMed  Google Scholar 

  8. Griffith J, Genant H. Bone mass and architecture determination: state of the art. Best Pract Res Clin Endocrinol Metab. 2008;22:737-764.

    Article  PubMed  Google Scholar 

  9. Richards J, Kavvoura F, Rivadeneira F, GFfO Consortium. Collaborative meta-analysis: association of 150 candidate genes with osteoporosis and osteoporotic fractures. Ann Int Med. 2009;151:528-537.

    PubMed  Google Scholar 

  10. Karsenty G. Transcriptional control of skeletogenesis. Annu Rev Genomics Hum Genet. 2008;9:183-196.

    Article  PubMed  CAS  Google Scholar 

  11. Flenniken AM, Osborne L, Anderson N, Disease CfMH. A Gja1 missense mutation in a mouse model of oculo­dentodigital ­dysplasia (ODDD). Development. 2005;132:4375-4386.

    Article  PubMed  CAS  Google Scholar 

  12. Ochotny N, Flenniken A, Owen C, et al. A point mutation in the V-ATPase subunit a3, R740S, uncouples ATP hydrolysis from proton transport and results in a dominant osteopetrosis phenotype. J Bone Miner Res. 2011 in press Feb 8. doi: 10.1002/.

    Google Scholar 

  13. Amizuka N, Davidson D, Liu H, et al. Signaling by fibroblast growth factor receptor 3 (FGFR3) and parathyroid hormone related protein (PTHrP) coordinate cartilage and bone development. Bone. 2003;34:13-25.

    Article  Google Scholar 

  14. Miao D, Liu H, Plut P, et al. Impaired endochondral bone development and osteopenia in Gli2 deficient mice. Exp Cell Res. 2003;294:210-222.

    Article  Google Scholar 

  15. Valverde-Franco G, Liu H, Davidson D, et al. Defective bone mineralization and osteopenia in young adult FGFR3-/- mice. Hum Mol Genet. 2004;13:271-284.

    Article  PubMed  CAS  Google Scholar 

  16. Richard S, Valverde-Franco G, Tremblay GA, et al. Ablation of the Sam68 RNA-binding protein protects mice from age-related bone loss. PLoS Genet. 2005;1:e74-e84.

    Article  PubMed  Google Scholar 

  17. Valverde-Franco G, Binette JS, Li W, et al. Defects in articular cartilage and early arthritis in fibroblast growth factor receptor 3 deficient mice. Hum Mol Genet. 2006;15:1783-1792.

    Article  PubMed  CAS  Google Scholar 

  18. Deckelbaum RA, Majithia A, Booker T, Henderson JE, Loomis CA. The homeoprotein Engrailed-1 has pleiotropic functions in calvarial intramembranous bone formation and remodeling. Development. 2006;133:63-74.

    Article  PubMed  CAS  Google Scholar 

  19. Lengner CJ, Steinman HA, Gagnon J, et al. Osteoblast differentiation and skeletal development are regulated by Mdm2-p53 signaling. J Cell Biol. 2006;172:909-921.

    Article  PubMed  CAS  Google Scholar 

  20. Haston CK, Li W, Li A, Lafleur M, Henderson JE. Persistent osteopenia in adult Cftr-deficient mice. Am J Respir Crit Care Med. 2008;177:309-315.

    Article  PubMed  Google Scholar 

  21. Rivas D, Li W, Akter R, Henderson J, Duque G. Accelerated features of age-related bone loss in Zmpste24 metalloproteinase-deficient mice. J Gerontol. 2009;10:1015-1024.

    Google Scholar 

  22. Marquis J, Gros P. Genetic analysis of resistance to infections in mice: A/J meets C57BL6/J. Curr Top Microbiol Immunol. 2008;321:27-57.

    Article  PubMed  CAS  Google Scholar 

  23. Beamer W, Donahue L, Rosen C, Baylink D. Genetic variability in adult bone density among inbred strains of mice. Bone. 1996;18:397-403.

    Article  PubMed  CAS  Google Scholar 

  24. Turner C, Hsieh Y, Muller R, et al. Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Miner Res. 2000;15:1126-1131.

    Article  PubMed  CAS  Google Scholar 

  25. Turner C, Hsieh Y, Muller R, et al. Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice. J Bone Miner Res. 2001;16:206-213.

    Article  PubMed  CAS  Google Scholar 

  26. Rosen CJ, Dimal HP, Veraeault D, et al. Circulating and skeletal insulin like growth factor 1 (IGF-1) concentrations in two inbred strains of mice with different bone mineral densities. Bone. 1997;21:217-223.

    Article  PubMed  CAS  Google Scholar 

  27. Delahunty K, Shultz K, Gronowicz G, et al. Congenic mice provide in vivo evidence for a genetic locus that modulates serum insulin-like growth factor-1 and bone acquisition. Endocrinology. 2006;147:3915-3923.

    Article  PubMed  CAS  Google Scholar 

  28. D’Ascenzo M, Meacham C, Kirzman J, et al. Mutation discovery in the mouse using genetically guided array capture and resequencing. Mamm Genome. 2009;20:424-436.

    Article  PubMed  Google Scholar 

  29. Colvin JS, Bohne BA, Harding GW, McEwen DG, Ornitz DM. Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. Nat Genet. 1996;12:390-397.

    Article  PubMed  CAS  Google Scholar 

  30. Deng C, Wynshaw-Boris A, Zhou F, Kuo A, Leder P. Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell. 1996;84:911-921.

    Article  PubMed  CAS  Google Scholar 

  31. Chappard D, Palle S, Alexandre C, Vico L, Riffat G. Bone embedding in pure methyl methacrylate at low temperature preserves enzyme activities. Acta Histochem. 1987;81:183-190.

    PubMed  CAS  Google Scholar 

  32. Williams B, Insogna K. Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone. J Bone Miner Res. 2009;24:171-178.

    Article  PubMed  CAS  Google Scholar 

  33. Boyde A, Jones S. Scanning electron microscopy of bone: instrument, specimen ans issues. Microsc Res Tech. 1996;33:92-120.

    Article  PubMed  CAS  Google Scholar 

  34. Marks S, Odgren P. Structure and development of the skeleton. In: Bilezekian J, Raisz L, Rodan G, eds. Principles of Bone Biology. San Diego: Academic; 2002:3-16.

    Google Scholar 

  35. Lvov B. Fifty years of atomic absorption spectrometry. J Anal Chem. 2005;60:382-392.

    Article  CAS  Google Scholar 

  36. Boskey A, Camacho N. FT-IR imaging of native and tissue-engineered bone and cartilage. Biomaterials. 2006;28:2465-2478.

    Article  PubMed  Google Scholar 

  37. Gentleman E, Swain R, Evans N, et al. Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation. Nat Mater. 2009;8:763-770.

    Article  PubMed  CAS  Google Scholar 

  38. Goodyear S, Gibson I, Skakle J, Wells R, Aspden R. A comparison of cortical and trabecular bone from C57 Black 6 mice using Raman spectroscopy. Bone. 2009;44:899-907.

    Article  PubMed  Google Scholar 

  39. Schulmerich M, Cole J, Kreider J, et al. Transcutaneous Raman spectroscopy of murine bone in vivo. Appl Spectrosc. 2009;63:286-295.

    Article  PubMed  CAS  Google Scholar 

  40. Mousny M, Banse X, Wise L, et al. The genetic influence on bone susceptibility to fluoride. Bone. 2006;39:1283-1289.

    Article  PubMed  CAS  Google Scholar 

  41. Yang R, Davies C, Archer C, Richards R. Immunohistochemistry of matrix markers in Technovit 9100 New-embedded undecalcified bone sections. Eur Cell Mater. 2003;6:57-71.

    PubMed  CAS  Google Scholar 

  42. Tamer E, Reis R. Progenitor and stem cells for bone and cartilage regeneration. J Tissue Eng Regen Med. 2009;3: 327-337.

    Article  PubMed  Google Scholar 

  43. Hasegawa T, Oizumi K, Yoshiko Y, Tanne K, Maeda N, Aubin J. The PPARgamma-selective ligand BRL-49653 differentially regulates the fate choices of rat calvaria versus rat bone marrow stromal cell populations. BMC Dev Biol. 2008;8:1-12.

    Article  Google Scholar 

  44. Aubin JE, Triffitt J. Mesenchymal stem cells and the osteoblast lineage. In: Bilezikian JP, Raisz LG, Rodan GA, eds. Principles of Bone Biology. 2nd ed. New York: Academic; 2002:59-81.

    Chapter  Google Scholar 

  45. Johnell O, Kanis J. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteo­poros Int. 2006;17:1726-1733.

    Article  PubMed  CAS  Google Scholar 

  46. Shapiro F. Bone development and its relation to fracture repair. The role mesenchymal osteoblasts and surface osteoblasts. Eur Cells Mater. 2008;15:53-76.

    CAS  Google Scholar 

  47. Duque D. Bone and fat connection in aging bone. Curr Opin Rheumatol. 2008;20:429-434.

    Article  PubMed  CAS  Google Scholar 

  48. Pasco J, Sanders KM, Hoekstra FM, Henry MJ, Nicholson GC, Kotowicz MA. The human cost of fracture. Osteoporos Int. 2005;16:2046-2052.

    Article  PubMed  Google Scholar 

  49. Jones A, Bucholz R, Bosse M, et al. Recombinant BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized controlled trial. J Bone Joint Surg Am. 2006;88:1431-1441.

    Article  PubMed  Google Scholar 

  50. Friedrich J, Moran S, Bishop A, Wood C, Shin A. Free vascularized fubular graft salvage of complications of long-bone allograft after tumor reconstruction. J Bone Joint Surg Am. 2008;90:93-100.

    Article  PubMed  Google Scholar 

  51. Gruber R, Koch H, Doll B, Tegtmeier F, Einhorn T, Hollinger J. Fracture healing in the elderly patient. Exp Gernotol. 2006;41:1080-1093.

    Article  Google Scholar 

  52. Khan Y, Yaszemski M, Mikos A, Laurencin C. Tissue engineering of bone: material and matrix considerations. J Bone Joint Surg Am. 2008;90:36-42.

    Article  PubMed  Google Scholar 

  53. Lee K, Chan C, Patil N, Goodman S. Cell therapy for bone regeneration: bench to bedside. J Biomed Mater Res B Appl Biomater. 2009;89:252-263.

    PubMed  Google Scholar 

  54. Mashimo T, Serikawa T. Rat resources in biomedical research. Curr Pharm Biotechnol. 2009;10:214-220.

    Article  PubMed  CAS  Google Scholar 

  55. Whitfield J, Morley P, Willick G. Parathyroid hormone, its fragments and their analogs for the treatment of osteoporosis. Treat Endocrinol. 2002;1:175-190.

    Article  PubMed  CAS  Google Scholar 

  56. Herbenick M, Sprott D, Still H, Lawless M. Effects of a cyclooxygenase 2 inhibitor on fracture healing in a rat model. Am J Orthop. 2008;37:133-137.

    Google Scholar 

  57. Miettinen S, Jaatinen J, Pelttari A, et al. Effect of locally administered zoledronic acid on injury-induced intramembranous bone regeneration and osseointegration of a titanium implant in rats. J Orthop Sci. 2009;14:431-436.

    Article  PubMed  CAS  Google Scholar 

  58. Boerckel J, Dupont K, Kolambkar Y, Lin A, Guldberg R. In vivo model for evaluating the effects of mechanical stimulation on tissue-engineered bone repair. J Biomech Eng. 2009;131:084502:1-5.

    Google Scholar 

  59. Ma D, Guan J, Normandin F, et al. Multifunctional nano-architecture for biomedical applications. Chem Mater. 2006; 18:1920-1927.

    Article  CAS  Google Scholar 

  60. Dalby M, Gadegaard N, Tare R, et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater. 2007;6:997-1003.

    Article  PubMed  CAS  Google Scholar 

  61. Ibasco S, Tamimi F, Meszaros R, et al. Magnesium-sputtered titanium for the formation of bioactive coatings. Acta Biomater. 2009;5:2338-2347.

    Article  PubMed  CAS  Google Scholar 

  62. Harvey E, Henderson J, Vengallatore S. Nanotechnology and bone healing. J Ortho Trauma. 2010;24:S25-S30.

    Article  Google Scholar 

  63. Brown R, Wiseman M, Chuo C, Cheema U, Nazhat S. Ultrarapid engineering of biomimetic materials and tissues: fabrication of nano- and microstructures by plastic compression. Adv Funct Mater. 2005;15:1762-1770.

    Article  CAS  Google Scholar 

  64. Bitar M, Brown R, Salih V, Kidane A, Knowles J, Nazhat S. Effect of cell density on osteoblastic differentiation and matrix degradation of biomimetic dense collagen scaffolds. Biomacromolecules. 2008;9:129-135.

    Article  PubMed  CAS  Google Scholar 

  65. Mudera V, Morgan M, Cheema U, Nazhat S, Brown R. Ultra-rapid engineered collagen constructs tested in an in vivo nursery site. J Tissue Eng Regen Med. 2007;1: ­192-198.

    Article  PubMed  CAS  Google Scholar 

  66. Buxton P, Bitar M, Gellynck K, et al. Dense collagen matrix accelerates osteogenic differentiation and rescues the apoptotic response to MMP inhibition. Bone. 2008;43:377-385.

    Article  PubMed  CAS  Google Scholar 

  67. Bonnarens F, Einhorn T. Production of a standard closed fracture in laboratory animal bone. J Orthop Res. 1984;2: 97-101.

    Article  PubMed  CAS  Google Scholar 

  68. Palomares K, Gleason R, Mason Z, et al. Mechanical stimulation alters tissue differentiation and molecular expression during bone healing. J Orthop Res. 2009;27:1123-1132.

    Article  PubMed  Google Scholar 

  69. Fu L, Tang T, Miao Y, Hao Y, Dai K. Effect of 1, 25-dihydroxy vitamin D3 on fracture healing and bone remodeling in ovariectomized rat femora. Bone. 2009;44:893-898.

    Article  PubMed  CAS  Google Scholar 

  70. Karp J, Sarraf F, Shoichet M, Davies J. Fibrin-filled scaffolds for bone-tissue engineering: an in vivo study. J Biomed Mater Res A. 2004;71:162-171.

    Article  PubMed  Google Scholar 

  71. Nagashima M, Sakai A, Uchida S, Tanaka S, Tanaka M, Nakamura T. Bisphosphonate (YM520) delays the repair of cortical bone defect after drill-hole injury by reducing terminal differentiation of osteoblasts in the mouse femur. Bone. 2005;36:502-511.

    Article  PubMed  CAS  Google Scholar 

  72. Majd H, Wipff P, Buscemi L, et al. A novel method of dynamic culture surface expansion improvesmesenchymal stem cell proliferation and phenotype. Stem Cells. 2009; 27:200-209.

    Article  PubMed  CAS  Google Scholar 

  73. Jabbarzadeh E, Starnes T, Khan Y, et al. Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy transplantation approach. Proc Natl Acad Sci USA. 2008;105:11099-11104.

    Article  PubMed  CAS  Google Scholar 

  74. Rosa A, de Oliveira P, Beloti M. Macroporous scaffolds associated with cells to construct a hybrid biomaterial for bone tissue engineering. Expert Rev Med Devices. 2008; 5:719-728.

    Article  PubMed  Google Scholar 

  75. LeNihouannen D, Komarova S, Gbureck U, Barralet J. Bioactivity of bone resorptive factor loaded on osteoconductive matrices: stability post-dehydration. Eur J Pharm Biopharm. 2008;70:813-818.

    Article  CAS  Google Scholar 

  76. Hacking S, Zuraw M, Harvey E, Tanzer M, Krygier J, Bobyn J. A physical vapor deposition method for controlled evaluation of biological response to biomaterial chemistry and topography. J Biomed Mater Res A. 2007;82:179-187.

    PubMed  CAS  Google Scholar 

  77. Hacking SA, Tanzer M, Harvey EJ, Krygier JJ, Bobyn JD. Relative contributions of chemistry and topography to the osseointegration of hydroxyapatite coatings. Clin Orthop Relat Res. 2002;405:24-38.

    Article  PubMed  Google Scholar 

  78. Hacking S, Harvey E, Roughly P, Tanzer M, Bobyn J. The response of mineralizing culture systems to microtextured and polished titanium surfaces. J Orthop Res. 2008;26: 1347-1354.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants from the Canadian Institutes of Health Research, Genome Québec, the Fonds de la recherche en sante Quebec sponsored Réseau de recherché en transgenèse du Québec, and the Réseau de recherche en santé buccodentaire et osseuse. Dr. C. Gao is a scholar of the MENTOR Strategic Training in Health Research program. The authors thank Ailian Li, Wei Li, and Huifen Wang for their invaluable assistance with the mouse phenotyping work and Dr. J. Seuntjens of the Medical Physics Unit, McGill University, for collaboration with the mouse irradiation studies.

Author information

Authors and Affiliations

  1. Department of Medicine and Surgery, McGill University Health Centre, Montreal General Hospital, Room A5.169, 1650 Cedar Ave., Montreal, Québec, H3G 1A4, Canada

    Janet E. Henderson

Authors
  1. Janet E. Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edward J. Harvey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Janet E. Henderson .

Editor information

Editors and Affiliations

  1. Nepean Hospital, Dept. Geriatric Medicine, University of Sydney, Penrith, 2750, New South Wales, Australia

    Gustavo Duque

  2. Department of Bone & Joint Disease, National Center for Geriatrics & Geronto, Obu-Aichi, Japan

    Ken Watanabe

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag London Limited

About this chapter

Cite this chapter

Henderson, J.E., Gao, C., Harvey, E.J. (2011). Skeletal Phenotyping in Rodents: Tissue Isolation and Manipulation. In: Duque, G., Watanabe, K. (eds) Osteoporosis Research. Springer, London. https://doi.org/10.1007/978-0-85729-293-3_2

Download citation

  • DOI: https://doi.org/10.1007/978-0-85729-293-3_2

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-292-6

  • Online ISBN: 978-0-85729-293-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation