Skip to main content
SpringerLink
Log in

Rabbit as a Model for the Study of Human Diseases

  • Chapter
Rabbit Biotechnology

Abstract

Although genetically modified mice are playing an essential role in the study of the expression and functions of individual genes, rabbits are useful animal models to extrapolate animal studies to humans. It is necessary that key gene expression and function are equivalent and close to human rather than the outward features or phenotype. For example, to study human hypercholesterolemia, the only hypercholesterolemia is insufficient, the lipoprotein profiles and enzymes in the lipoprotein metabolism of animal models are important for translational medicine. Lipoprotein metabolism of rabbits resembles humans closely. In addition, histopathological and/or immunohistochemical fea tures of the tissues of disease similar to humans are important. In this field, spontaneous hypercholesterolemic rabbits (WHHL and WHHLMI rabbits) have contributed to the elucidation of lipoprotein metabolism, atherogenesis, and to the development of therapeutic compounds, such as statins. Recently, a number of transgenic rabbits have been developed and they also contribute to the study of cardiac function and infectious diseases. Furthermore, rabbits are useful for studies of orthopedic surgery, cardiovascular surgery, and neoplastic diseases. Rabbit models have contributed not only to the mechanistic studies of human diseases but also to the development of therapeutic compounds, devices, or techniques for therapeutics. Applying these animal models in translational researches promotes the elucidations of human diseases.

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

Access this chapter

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 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anitschkow NN, Chalatow S (Translated by Pelias MZ). (1983) On experimental cholesterin steatosis and its significance in the origin of some pathological processes. Arteriosclerosis 3: 178–182. (The original article: Ueber experimentelle cholesterinsteatose und ihre bedeutung für die entstehung einiger pathologischer prozesse. Zentralbl Allg Pathol Pathol Anat 1913; 24: 1–9.)

    Google Scholar 

  • Ardern HA, Benson GM, Suckling KE, Caslake MJ, Shepherd J, Packard CJ. (1999) Apolopoprotein B overproduction by the perfused liver of the St. Thomas' mixed hyperlipi-demic (SMHL) rabbit. J Lipid Res 40: 2234–2243.

    CAS  Google Scholar 

  • Brunner M, Peng X, Liu GX, Ren Z, Ziv O, Choi B, Mathur R, Hajjiri M, Odening KE, Steinberg E, Folco EJ, Pringa E, Centracchio J, Macharzina RR, Donahay T, Schofield L, Rana N, Kirk M, Mitchell GF, Poppas A, Zehender M, Koren G. (2008) Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. J Clin Invest 118: 2246–2259.

    PubMed  CAS  Google Scholar 

  • Chartrand C, O'Regan S, Robitaille P, Pino-Blonde M. (1979) Delayed rejection of cardiac xenografts in C6-defficient rabbits. Immunology 38: 245–248.

    PubMed  CAS  Google Scholar 

  • Cybulsky MI, Gimbrone MA. (1991) Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251: 788–791.

    Article  PubMed  CAS  Google Scholar 

  • De Roos B, Caslake MJ, Ardern HA, Benson GM, Suckling KE, Packard CJ. (2001) Insulin resistance in the St. Thomas' mixed hyperlipidemic (SMHL) rabbit, a model for familial combined hyperlipidemia. Atherosclerosis 156: 249–254.

    Article  PubMed  Google Scholar 

  • De Roos B, Caslake MJ, Milliner K, Benson GM, Suckling KE, Packard CJ. (2005) Characterisation of the lipoprotein structure in the St. Thomas' mixed hyperlipidemic (SMHL) rabbit. Atherosclerosis 181: 63–68.

    Google Scholar 

  • Fan J, Watanabe T. (2003) Transgenic rabbits as therapeutic protein bioreactors and human disease models. Pharmacol Ther 99: 261–282.

    Article  PubMed  CAS  Google Scholar 

  • Fleet JC, Clinton SK, Salomon RN, Loppnow H, Libby P. (1992) Atherogenic diets enhance endoxin-stimulated interleukin-1 and tumor necrosis factor gene expression in rabbit aorta. J Nutr 122: 294–305.

    PubMed  CAS  Google Scholar 

  • Galis ZS, Sukhova GK, Kränzhofer R, Clark S, Libby P. (1995) Macrophage foam cells from experimental atheroma constitutively produce matrix-degradation proteins. Proc Natl Acad Sci USA 92: 402–406.

    Article  PubMed  CAS  Google Scholar 

  • Garibaldi BA, Goad MEP. (1998) Lipid keratopathy in the Watanabe (WHHL) rabbit. Vet Pathol 25: 173–174.

    Article  Google Scholar 

  • Goldstein JL, Kita T, Brown MS. (1983) Defective lipoprotein receptors and atherosclerosis: lessons from an animal counterpart of familial hypercholesterolemia. N Engl J Med 309: 288–296.

    PubMed  CAS  Google Scholar 

  • Hasegawa T, Okada K, Takano Y, Hiraishi Y, Okita Y. (2007) Autologous fibrin-coated small-caliber vascular prostheses improve antithrombogenecity by reducing immunologic response. J Thorac Cardiovasc Surg 133: 1268–1276.

    Article  PubMed  CAS  Google Scholar 

  • Hoshiba Y, Hatakeyama K, Tanabe T, Asada Y, Goto S. (2006) Co-localization of von Willebrand factor with platelet thrombi, tissue factor and platelets with fibrin, and consistent presence of inflammatory cells in coronary thrombi obtained by an aspiration device from patients with acute myocardial infarction. J Thromb Haemost 3: 1140–1120.

    Google Scholar 

  • Hu J, Peng X, Budgeon LR, Cladel NM, Balogh KK, Christensen ND. (2007) Establishment of a cottontail rabbit papillomavirus/HLA-A2.1 transgenic rabbit model. J Virol 81: 7171–7177.

    Article  PubMed  CAS  Google Scholar 

  • Ikeda R, Fujioka H, Nagura I, Kokubu T, Toyokawa N, Inui A, Makino T, Kaneko H, Doita M, Kurosaka M. (2009) The effects of porosity and mechanical property of a synthetic polymer scaffold on repair of osteochondral defects. Int Orthop (in press).

    Google Scholar 

  • Ishida K, Kuroda R, Miwa M, Tabata Y, Hokugo A, Kawamoto T, Sasaki K, Doita M, Kurosaka M. (2007) The regenerative effects of platelet-rich plasma on meniscal cells in vitro and its in vivo application with biodegradable gelatin hydrogel. Tissue Eng 13: 1103–1112.

    Article  PubMed  CAS  Google Scholar 

  • (2007) Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with atherosclerotic plaque instability-analysis in hypercholesterolemic rabbits. Atherosclerosis 195: 48–56.

    Article  PubMed  CAS  Google Scholar 

  • Ito T, Yamada S, Shiomi M. (2004) Progression of coronary atherosclerosis relates to the onset of myocardial infarction in an animal model of spontaneous myocardial infarction (WHHLMI rabbits). Exp Anim 53: 339–334.

    Article  PubMed  CAS  Google Scholar 

  • Iwata A, Miura S, Imaizumi B, Saku K. (2007) Measurement of atherosclerotic plaque volume in hyperlipidemic rabbit aorta by intravascular ultrasound. J Cardiol 50: 229–234.

    PubMed  Google Scholar 

  • Jiang HJ, Zhang ZR, Shen BZ, Wan Y, Guo H, Shu SJ. (2008) Functional CT for assessment of early vascular physiology in liver tumors. Hepatobiliary Pancreat Dis Int 7: 497–502.

    PubMed  Google Scholar 

  • Kawai T, Ito T, Ohwada K, Mera Y, Matsushita M, Tomoike H. (2006) Hereditary postprandial hypertriglyceridemic rabbit exhibits insulin resistance and central obesity: a novel model of metabolic syndrome. Arterioscler Thromb Vasc Biol 26: 2752–2757.

    Article  PubMed  CAS  Google Scholar 

  • Kawanishi Y, Okada K, Tanala H, Yamashota T, Nakagiri K, Okita Y. (2007) The adverse effect of back-bleeding from lumber arteries on spinal cord pathophysiology in a rabbit model. J Thorac Cardiovasc Surg 133: 1553–1558.

    Article  PubMed  Google Scholar 

  • Kidd JG, Rous P. (1940) A transplantable rabbit carcinoma originating in a virus-induced papil-loma and containing the virus in masked or altered form. J Exp Med 71: 813–838.

    Article  PubMed  Google Scholar 

  • Kita T, Brown MS, Watanabe Y, Goldstein JL. (1981) Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholes-terolemia. Proc Natl Acad Sci USA 78: 2268–2272.

    Article  PubMed  CAS  Google Scholar 

  • Kozarsky KF, Bonen DK, Giannoni F, Funahashi T, Wilson JM, Davivson NO. (1996) Hepatic expression of the catalytic subunit of the apolipoprotein B mRNA editing enzyme (apobec-1) ameliorates hypercholesterolemia in LDL receptor-deficient rabbits. Hum Gene Ther 7: 973–977.

    Article  Google Scholar 

  • La Ville A, Turner PR, Pittilo RM, Martini S, Marenah CB, Rowles PM, Morris G. (1987) Thomson GA, Woolf N, Lewis B. Hereditary hyperlipidemia in the rabbit due to overproduction of lipoproteins. I. Biochemical studies. Arteriosclerosis 7: 105–112

    Google Scholar 

  • Manabe YC, Kesavan AK, Lopez-Molina J, Hatem CL, Brooks M, Fujiwara R, Hochstein K, Pitt MLM, Tufariello J, Chan J, McMurray DN, Bishai WR, Dannenberg AM, Mendez S. (2008) The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome. Tuberculosis 88: 187–196.

    Article  PubMed  CAS  Google Scholar 

  • Mendez S, Hatem CL, Kesavan AK, Lopez-Molina J, Pitt ML, Dannenberg AM Jr, Manabe YC. (2008) Susceptibility to tuberculosis: composition of tuberculous granulomas in Thorbecke and outbred New Zealand white rabbits. Vet Immunol Immunopathol 122: 167–174.

    Article  PubMed  CAS  Google Scholar 

  • Meding J, Urich M, Licha K, Reinhardt M, Misselwitz B, Fayad ZA, Weinmann HJ. (2007) Magnetic resonance imaging of atherosclerosis by targeting extracellular matrix deposition with Gadofluorine M. Contrast Media Mol Imag 2: 120–129.

    Article  CAS  Google Scholar 

  • Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Airaksinen KEJ, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang I, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull W Jr, Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, and Willerson JT. (2003) From vulnerable plaques to vulnerable patients, a call for new definitions and risk assessment strategies: Part I. Circulation 108: 1664–1672.

    Article  PubMed  Google Scholar 

  • Nakayama J, Fujioka H, Nagura I, Kokubu T, Makino T, Kuroda R, Tabata Y, Kurosaka M. (2009) The effect of fibroblast growth factor-2 on autologous osteochondral transplantation. Int Orthop 33: 275–280.

    Article  PubMed  Google Scholar 

  • Odening KE, Hyder O, Chaves L, Schofield L, Brunner M, Kirk M, Zehender M, Peng X, Koren G. (2008) Pharmacogenomics of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization. Am J physiol Heart Circ Physiol 295: H2264–H2272.

    Article  PubMed  CAS  Google Scholar 

  • Ogawa M, Magata Y, Kato T, Hatano K, Ishino S, Mukai T, Shiomi M, Ito K, Saji H. (2006) Application of 18F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerable atherosclerotic plaques. J Nucl Med 47: 1845–1850.

    PubMed  CAS  Google Scholar 

  • Ohira T, Okuma T, Matsuoka T, Wada Y, Nakamura K, Watanabe Y, Inoue Y. (2009) FDG-MicroPET and diffusion-weighted MR image evaluation of early changes after radiofrequency ablation in implanted VX2 tumors in rabbits. Cardiovasc Intervent Radiol 32: 114–120.

    Article  PubMed  Google Scholar 

  • Rosenfeld ME, Tsukada T, Gown AM, Ross R. (1987) Fatty streak initiation in Watanabe heritable hyperlipidemic and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis 7: 9–23.

    PubMed  CAS  Google Scholar 

  • Rosenfeld ME, Ylä-herttuala S, Lipton BA, Ord VA, Witztum JL, Steinberg D. (1992) Macrophage colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans. Am J Pathol 140: 291–300.

    PubMed  CAS  Google Scholar 

  • Rother K, Rother U, Muller-Eberhard HJ, Nilsson UR. (1966) Defficiency of the sixth component of complement in rabbits with an inherited complement defect. J Exp Med 124: 773–785.

    Article  PubMed  CAS  Google Scholar 

  • Schmiedt W, Kinscherf R, Deigner HP, Kamencic H, Nauen O, Kilo J, Oelert H, Metz J, Bhakdi S. (1998) Complement C6 deficiency protects against diet-induced atherosclerosis in rabbits. Arterioscler Throm Vasc Biol 18: 1790–1795.

    CAS  Google Scholar 

  • Shiomi M, Fan J. (2008) Unstable coronary plaques and cardiac events in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits: questions and quandaries. Curr Opin Lipidol 19: 631–636.

    Article  PubMed  CAS  Google Scholar 

  • Shiomi M, Ito T. (1999a) Effect of cerivastatin sodium, a new inhibitor of HMG-CoA reductase, on plasma lipid levels, progression of atherosclerosis, and the lesional composition in the plaques of WHHL rabbits. Br J Pharmacol 126: 961–968.

    Article  CAS  Google Scholar 

  • Shiomi M, Ito T, Tsukada T, Tsujita Y, Horikoshi H. (1999b) Combination treatment with troglita-zone, an insulin action enhancer, and pravastatin, an inhibitor of HMG-CoA reductase, shows synergistic effect on atherosclerosis of WHHL rabbits. Atherosclerosis 42: 345–353.

    Article  Google Scholar 

  • Shiomi M, Ito T, Tsukada T, Yata T, Ueda M. (1994) Cell compositions of coronary and aortic atherosclerotic lesions differ; An immunohistochemical study. Arterioscler Thromb 14: 931–937.

    PubMed  CAS  Google Scholar 

  • Shiomi M, Ito T, Tsukada T, Yata T, Watanabe Y, Tsujita Y, Fukami M, Fukushige J, Hosokawa T, Tamura A. (1995) Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques: effect of pravastatin sodium on atherosclerosis in mature WHHL rabbits. Arterioscler Thromb Vasc Biol 15: 1938–1944.

    PubMed  CAS  Google Scholar 

  • Shiomi M, Ito T, Yamada S, Kawashima S, Fan J. (2003) Development of an animal model for spontaneous myocardial infarction (WHHLMI Rabbit). Arterioscler Thromb Vasc Biol 23: 1239–1244.

    Article  PubMed  CAS  Google Scholar 

  • Shiomi M, Yamada S, Ito T. (2005) Atheroma stabilizing effects of simvastatin due to depression of macrophages or lipid accumulation in the atheromatous plaques of coronary atherosclerosis-prone WHHL rabbits. Atherosclerosis 178: 287–294.

    Article  PubMed  CAS  Google Scholar 

  • Son YC, Zilversmit DB. (1986) Increased lipid transfer activities in hyperlipidemic rabbit plasma. Arteriosclerosis 6: 345–351.

    PubMed  CAS  Google Scholar 

  • Steen H, Lima JA, Chatterjee S, Kolmakova A, Gao F, Rodrigues ER, Stuber M. (2007) High-resolution three-dimensional aortic magnetic resonance angiography and quantitative vessel wall characterization of different atherosclerotic stages in a rabbit model. Invest Radiol 42: 614–621.

    Article  PubMed  Google Scholar 

  • Tanzawa K, Shimada Y, Kuroda M, Tsujita Y, Arai M, Watanabe Y. (1980) WHHL-rabbit: a low density lipoprotein receptor-deficient animal model for familial hypercholesterolemia. FEBS Lett 118: 81–84.

    Article  PubMed  CAS  Google Scholar 

  • Tsujita Y, Kuroda M, Shimada Y, Tanzawa K, Arai M, Kaneko I, Tanaka M, Masuda H, Tarumi C, Watanabe Y, Fujii S. (1986) CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species. Biochim Biophys Acta 877: 50–60.

    PubMed  CAS  Google Scholar 

  • Virmani S, Rhee TK, Ryu RK, Sato KT, Lewandowski RJ, Mulcahy MF, Kulik LM, Szolc-Kowalska B, Woloschak GE, Yang GY, Salem R, Larsin AC, Omary RA. (2008) Comparison of hypoxia-inducible factor-1alpha expression before and after transcatheter arterial ambolisa-tion in rabbit VX2 liver tumors. J Vasc Interv Radiolo 19: 1483–1489.

    Article  Google Scholar 

  • Watanabe Y. (1980) Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit). Atherosclerosis 36: 261–268.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe Y, Ito T, Saeki M, Kuroda M, Tanzawa K, Mochizuki M, Tsujita Y, Arai M. (1981) Hypolipidemic effects of CS-500 (ML-236B) in WHHL-rabbit, a heritable animal model for hyperlipidemia. Atherosclerosis 38: 27–31.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe Y, Ito T, Shiomi M. (1985) The effect of selective breeding on the development of coronary atherosclerosis. Atherosclerosis 56: 71–79.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe Y, Ito T, Shiomi M, Tsujita Y, Kuroda M, Arai M, Fukami M, Tamura A. (1988) Preventive effect of pravastatin sodium, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis and xanthoma in WHHL rabbits. Biochim Biophys Acta 960: 294–302.

    PubMed  CAS  Google Scholar 

  • Yamamoto T, Bishop RW, Brown MS, Goldstein JL, Russell DW. (1986) Deletion in cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit. Science 232: 1230–1237.

    Article  PubMed  CAS  Google Scholar 

  • Yamashita A, Furukoli E, Marutsuka K, Hatakeyama K, Yamamoto H, Tamura S, Ikeda Y, Sumiyoshi A, Asada Y. (2004) Increased vascular wall thrombogenicity combined with reduced blood flow promotes occlusive thrombus formation in rabbit femoral artery. Arterioscler Thromb Vasc Biol 24: 2420–2424.

    Article  PubMed  CAS  Google Scholar 

  • Ylä-Herrttuala S, Lipton BA, Rosenfeld ME, Särkioja T, Yoshimura T, Leonard EJ, Witztum JL, Steiberg D. (1991) Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. Proc Natl Acd Sci USA 88: 5252–5256.

    Article  Google Scholar 

  • Zhang B, Saku K, Hirata K, Liu R. (1991) Tateishi K, Yamamoto K, Arakawa K. Insulin resistance observed in WHHL rabbits. Atherosclerosis 91: 277–278.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Experimental Animals, Kobe University School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Masashi Shiomi

Authors
  1. Masashi Shiomi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Research in Agronomy, Jouy en Josas, France

    Louis-Marie Houdebine (Doctor) (Doctor)

  2. Department of Molecular Pathology, Interdisciplinary Graduate, School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan

    Jianglin Fan (Chairman and Professor) (Chairman and Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science + Business Media B.V.

About this chapter

Cite this chapter

Shiomi, M. (2009). Rabbit as a Model for the Study of Human Diseases. In: Houdebine, LM., Fan, J. (eds) Rabbit Biotechnology. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2227-1_7

Download citation

Publish with us

Policies and ethics

Search

Navigation