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Life Sciences Division, NASA Ames Research Center, Moffett Field, California 94035-1000
Since its inception at the National Aeronautics and Space Administration (NASA) Ames Research Center in the mid-1970s, many laboratories around the world have used the rat hindlimb unloading model to simulate weightlessness and to study various aspects of musculoskeletal loading. In this model, the hindlimbs of rodents are elevated to produce a 30° head-down tilt, which results in a cephalad fluid shift and avoids weightbearing by the hindquarters. Although several reviews have described scientific results obtained with this model, this is the first review to focus on the technical aspects of hindlimb unloading. This review includes a history of the technique, a brief comparison with spaceflight data, technical details, extension of the model to mice, and other important technical considerations (e.g., housing, room temperature, unloading angle, the potential need for multiple control groups, age, body weight, the use of the forelimb tissues as internal controls, and when to remove animals from experiments). This paper is intended as a reference for researchers, reviewers of manuscripts, and institutional animal care and use committees. Over 800 references, related to the hindlimb unloading model, can be accessed via the electronic version of this article.
simulated weightlessness; hindlimb suspension; altered gravity; mechanical load; animal model
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U. T. Iwaniec, T. J. Wronski, D. Amblard, Y. Nishimura, M. C. H. van der Meulen, C. E. Wade, M. A. Bourgeois, C. D. Damsky, and R. K. Globus Effects of disrupted {beta}1-integrin function on the skeletal response to short-term hindlimb unloading in mice J Appl Physiol, February 1, 2005; 98(2): 690 - 696. [Abstract] [Full Text] [PDF]
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M. J. Sullivan, E. M. Hasser, J. A. Moffitt, S. B. Bruno, and J. T. Cunningham Rats exhibit aldosterone-dependent sodium appetite during 24 h hindlimb unloading J. Physiol., June 1, 2004; 557(2): 661 - 670. [Abstract] [Full Text] [PDF]
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J. C. L. Tou, R. E. Grindeland, and C. E. Wade Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E425 - E433. [Abstract] [Full Text]
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H. X Nguyen and J. G Tidball Null mutation of gp91phox reduces muscle membrane lysis during muscle inflammation in mice J. Physiol., December 15, 2003; 553(3): 833 - 841. [Abstract] [Full Text] [PDF]
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T. E. Hefferan, G. L. Evans, S. Lotinun, M. Zhang, E. Morey-Holton, and R. T. Turner Effect of gender on bone turnover in adult rats during simulated weightlessness J Appl Physiol, November 1, 2003; 95(5): 1775 - 1780. [Abstract] [Full Text] [PDF]
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J. Frenette, N. Chbinou, C. Godbout, D. Marsolais, and P. S. Frenette Macrophages, not neutrophils, infiltrate skeletal muscle in mice deficient in P/E selectins after mechanical reloading Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R727 - R732. [Abstract] [Full Text] [PDF]
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H. Aviles, T. Belay, K. Fountain, M. Vance, B. Sun, and G. Sonnenfeld Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions J Appl Physiol, August 1, 2003; 95(2): 491 - 496. [Abstract] [Full Text] [PDF]
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 A. H. Casse, D. Desplanches, M. H. Mayet-Sornay, M. Raccurt, S. Jegou, and G. Morel Growth Hormone Receptor Expression in Atrophying Muscle Fibers of Rats Endocrinology, August 1, 2003; 144(8): 3692 - 3697. [Abstract] [Full Text] [PDF]
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H. X Nguyen and J. G Tidball Expression of a muscle-specific, nitric oxide synthase transgene prevents muscle membrane injury and reduces muscle inflammation during modified muscle use in mice J. Physiol., July 15, 2003; 550(2): 347 - 356. [Abstract] [Full Text] [PDF]
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L.-F. Zhang, B. Sun, X.-S. Cao, C. Liu, Z.-B. Yu, L.-N. Zhang, J.-H. Cheng, Y.-H. Wu, and X.-Y. Wu Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity J Appl Physiol, July 1, 2003; 95(1): 207 - 218. [Abstract] [Full Text] [PDF]
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H. Aviles, T. Belay, K. Fountain, M. Vance, and G. Sonnenfeld Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions J Appl Physiol, July 1, 2003; 95(1): 73 - 80. [Abstract] [Full Text] [PDF]
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P. J. Mueller and E. M. Hasser Enhanced sympathoinhibitory response to volume expansion in conscious hindlimb-unloaded rats J Appl Physiol, May 1, 2003; 94(5): 1806 - 1812. [Abstract] [Full Text] [PDF]
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M. R. Allen and S. A. Bloomfield Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats J Appl Physiol, February 1, 2003; 94(2): 642 - 650. [Abstract] [Full Text] [PDF]
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J. G Tidball and M. J Spencer Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during murine muscle disuse J. Physiol., December 15, 2002; 545(3): 819 - 828. [Abstract] [Full Text] [PDF]
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 J. Tou, A. Ronca, R. Grindeland, and C. Wade Models to Study Gravitational Biology of Mammalian Reproduction Biol Reprod, December 1, 2002; 67(6): 1681 - 1687. [Abstract] [Full Text] [PDF]
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