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Full text of this paper is not available in the ETD Center. Copies may be available for inter-library loan from University of Cincinnati or may be available for purchase from Proquest/UMI

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GENETICALLY MANIPULATED MOUSE MODELS FOR THE STUDY OF INSULIN-LIKE GROWTH FACTOR I IN BONE

ZHANG, MEI
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1014729983

Abstract Details

2002, PhD, University of Cincinnati, Medicine : Pathobiology and Molecular Medicine.
Insulin-like growth factor I (IGF-I) exerts anabolic effects on bone and is thought to amplify other osteogenic signals. However, the cellular and molecular mechanisms that mediate the anabolic actions of IGF-I have been difficult to address experimentally primarily due to the complexity of the IGF system. To study the local actions of IGF-I and its regulation by binding protein 4 (IGFBP-4) in skeletal tissue in a physiological context, I have developed mouse models with either overexpression of IGFBP-4 in osteoblasts or conditional disruption of the gene encoding the type I IGF receptor, Igf1r gene, in osteoblasts. Mice with overexpression of IGFBP-4 in bone osteoblasts exhibited reduced bone formation and turnover and severely impaired skeletal growth with global growth retardation. These effects were attributed to the sequestration of IGF-I by IGFBP-4 with consequent impairment of IGF-I actions. Osteoblast-specific disruption of the Igf1r gene reduced trabecular bone volume and severely impaired mineralization of bone matrix. Deficient IGF-I signaling led to a compensatory state of accelerated trabecular bone turnover. These studies established valuable models to further investigate the role of IGF-I signaling in bone.
Dr. Thomas Clemens (Advisor)
1 p.
Biology, Molecular
insulin-like growth factor (IFG-I); bone osteoblast; transgenic

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Citations

  • ZHANG, M. (2002). GENETICALLY MANIPULATED MOUSE MODELS FOR THE STUDY OF INSULIN-LIKE GROWTH FACTOR I IN BONE [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1014729983

    APA Style (7th edition)

  • ZHANG, MEI. GENETICALLY MANIPULATED MOUSE MODELS FOR THE STUDY OF INSULIN-LIKE GROWTH FACTOR I IN BONE. 2002. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1014729983.

    MLA Style (8th edition)

  • ZHANG, MEI. "GENETICALLY MANIPULATED MOUSE MODELS FOR THE STUDY OF INSULIN-LIKE GROWTH FACTOR I IN BONE." Doctoral dissertation, University of Cincinnati, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1014729983

    Chicago Manual of Style (17th edition)

ucin1014729983
© 2002, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.
Release 3.2.12