Skip to main content
SpringerLink
Log in

Animal Models of Lung Disease

  • Chapter
Molecular Pathology of Lung Diseases

Part of the book series: Molecular Pathology Library ((MPLB,volume 1))

Abstract

The lung is a complex organ composed of many different cell types. Its architecture is difficult to dissect so that a researcher can analyze specific pathways and early lesions. Animal models afford the opportunity for investigators to experimentally manipulate a number of controlled variables such as strain of animal, environment, and the genome in order to investigate the molecular interactions involved in the pathogenesis of many lung diseases.1 They also provide a unique opportunity to test potential therapeutic interventions. Transgenic mouse technology has provided a powerful tool for both neoplastic and noneoplastic disease investigation. Although the basic molecular biology terminology is covered in the first two chapters of this book, it is convenient to briefly review it here regarding the development of transgenic mice.

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 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

  1. Kumar RK. Experimental models in pulmonary pathology. Pathology 1995;27(2):130–132.

    Article  CAS  PubMed  Google Scholar 

  2. Argmann C, Dierich A, Auwrex J. Current Protocols in Molecular Biology. John Wiley & Sons; 2006.

    Google Scholar 

  3. Brusselle GG, Bracke KR, Maes AI, et al. Murine models of COPD. Pulm Pharmacol Ther 2006;19:155–165.

    Article  CAS  PubMed  Google Scholar 

  4. Paigen K. A miracle enough: the power of mice. Nat Med 1995;1(3):215–220.

    Article  CAS  PubMed  Google Scholar 

  5. Glasser SW, Korfhagen TR, Wert SE, Whitsett JA. Transgenic models for study of pulmonary development and disease. Am J Physiol 1994;267(5 Pt 1):L489–L497.

    CAS  PubMed  Google Scholar 

  6. Ho YS. Transgenic models for the study of lung biology and disease. Am J Physiol 1994;266(4 Pt 1):L319–L353.

    CAS  PubMed  Google Scholar 

  7. Shapiro SD. Animal models for COPD. Chest 2000;117(5 Suppl 1):223S–227S.

    Article  CAS  PubMed  Google Scholar 

  8. Shapiro SD. Animal models for chronic obstructive pulmonary disease: age of klotho and Marlboro mice. Am J Respir Cell Mol Biol 2000;22(1):4–7.

    CAS  PubMed  Google Scholar 

  9. Lucey EC. Experimental emphysema. Clin Chest Med 1983;4(3):389–403.

    CAS  PubMed  Google Scholar 

  10. Snider GL, Lucey EC, Stone PJ. Animal models of emphysema. Am Rev Respir Dis 1986;133(1):149–169.

    CAS  PubMed  Google Scholar 

  11. Guerassimov A, Hoshino Y, Takubo Y, et al. The development of emphysema in cigarette smoke-exposed mice is strain dependent. Am J Respir Crit Care Med 2004;170(9):974–980.

    Article  PubMed  Google Scholar 

  12. Bartalesi B, Cavarra E, Fineschi S, et al. Different lung responses to cigarette smoke in two strains of mice sensitive to oxidants. Eur Respir J 2005;25(1):15–22.

    Article  CAS  PubMed  Google Scholar 

  13. Valentine R, Rucker RB, Chrisp CE, Fisher GL. Morphological and biochemical features of elastase-induced emphysema in strain A/J mice. Toxicol Appl Pharmacol 1983;68(3):451–461.

    Article  CAS  PubMed  Google Scholar 

  14. Gross P, Pfitzer EA, Tolker E, Babyak MA, Kaschak M. Experimental emphysema: its production with papain in normal and silicotic rats. Arch Environ Health 1965;11:50–58.

    CAS  PubMed  Google Scholar 

  15. Shiomi T, Okada Y, Foronjy R, et al. Emphysematous changes are caused by degradation of type III collagen in transgenic mice expressing MMP-1. Exp Lung Res 2003;29(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  16. Foronjy RF, Okada Y, Cole R, D’Armiento J. Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung. Am J Physiol Lung Cell Mol Physiol 2003;284(5):L727–L737.

    CAS  PubMed  Google Scholar 

  17. Zheng T, Zhu Z, Wang Z, et al. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase-and cathepsin-dependent emphysema. J Clin Invest 2000;106(9):1081–93.

    Article  CAS  PubMed  Google Scholar 

  18. Wang Z, Zheng T, Zhu Z, et al. Interferon gamma induction of pulmonary emphysema in the adult murine lung. J Exp Med 2000;192(11):1587–1600.

    Article  CAS  PubMed  Google Scholar 

  19. Elkington PT, Friedland JS. Matrix metalloproteinases in destructive pulmonary pathology. Thorax 2006;61(3):259–266.

    Article  CAS  PubMed  Google Scholar 

  20. Elwood W, Lotvall JO, Barnes PJ, Chung KF. Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats. J Allergy Clin Immunol 1991;88(6):951–960.

    Article  CAS  PubMed  Google Scholar 

  21. Nagai H, Yamaguchi S, Inagaki N, et al. Effect of anti-IL-5 monoclonal antibody on allergic bronchial eosinophilia and airway hyperresponsiveness in mice. Life Sci 1993;53(15):PL243–PL247.

    Article  CAS  PubMed  Google Scholar 

  22. Renz H, Saloga J, Bradley KL, et al. Specific V beta T cell subsets mediate the immediate hypersensitivity response to ragweed allergen. J Immunol 1993;151(4):1907–1917.

    CAS  PubMed  Google Scholar 

  23. Kung TT, Jones H, Adams GK 3rd, et al. Characterization of a murine model of allergic pulmonary inflammation. Int Arch Allergy Immunol 1994;105(1):83–90.

    Article  CAS  PubMed  Google Scholar 

  24. Chavez J, Young HW, Corry DB, Lieberman MW. Interactions between leukotriene C4 and interleukin 13 signaling pathways in a mouse model of airway disease. Arch Pathol Lab Med 2006;130(4):440–446.

    CAS  PubMed  Google Scholar 

  25. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989;245(4922):1073–1080.

    Article  CAS  PubMed  Google Scholar 

  26. Buchwald M, Tsui LC, Riordan JR. The search for the cystic fibrosis gene. Am J Physiol 1989;257(2 Pt 1):L47–L52.

    CAS  PubMed  Google Scholar 

  27. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989;245(4922):1066–1073.

    Article  CAS  PubMed  Google Scholar 

  28. Rommens JM, Iannuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 1989;245(4922):1059–1065.

    Article  CAS  PubMed  Google Scholar 

  29. Snouwaert JN, Brigman KK, Latour AM, et al. An animal model for cystic fibrosis made by gene targeting. Science 1992;257(5073):1083–1088.

    Article  CAS  PubMed  Google Scholar 

  30. Davidson DJ, Rolfe M. Mouse models of cystic fibrosis. Trends Genet 2001;17(10):S29–S37.

    Article  CAS  PubMed  Google Scholar 

  31. Guilbault C, Saeed Z, Downey GP, Radzioch D. Cystic fibrosis mouse models. Am J Respir Cell Mol Biol 2007;36(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  32. Frizzell RA, Pilewski JM. Finally, mice with CF lung disease. Nat Med 2004;10(5):452–454.

    Article  CAS  PubMed  Google Scholar 

  33. Mall M, Grubb BR, Harkema JR, et al. Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat Med 2004;10(5):487–493.

    Article  CAS  PubMed  Google Scholar 

  34. Fleischman RW, Baker JR, Thompson GR, et al. Bleomycininduced interstitial pneumonia in dogs. Thorax 1971;26(6):675–682.

    Article  CAS  PubMed  Google Scholar 

  35. Adamson IY, Bowden DH. The pathogenesis of bleomycininduced pulmonary fibrosis in mice. Am J Pathol 1974;77(2):185–197.

    CAS  PubMed  Google Scholar 

  36. Adamson IY, Bowden DH. Bleomycin-induced injury and metaplasia of alveolar type 2 cells. Relationship of cellular responses to drug presence in the lung. Am J Pathol 1979;96(2):531–544.

    CAS  PubMed  Google Scholar 

  37. Snider GL, Hayes JA, Korthy AL. Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin: pathology and stereology. Am Rev Respir Dis 1978;117(6):1099–1108.

    CAS  PubMed  Google Scholar 

  38. Borzone G, Moreno R, Urrea R, et al. Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2001;163(7):1648–1653.

    CAS  PubMed  Google Scholar 

  39. Popenoe D. Effects of paraquat aerosol on mouse lung. Arch Pathol Lab Med 1979;103(7):331–334.

    CAS  PubMed  Google Scholar 

  40. Yoshida M, Sakuma J, Hayashi S, et al. A histologically distinctive interstitial pneumonia induced by overexpression of the interleukin 6, transforming growth factor beta 1, or platelet-derived growth factor B gene. Proc Natl Acad Sci USA 1995;92(21):9570–9574.

    Article  CAS  PubMed  Google Scholar 

  41. Katsuma S, Nishi K, Tanigawara K, et al. Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNA microarray-based gene expression profiling. Biochem Biophys Res Commun 2001;288(4):747–751.

    Article  CAS  PubMed  Google Scholar 

  42. Driessens J, Clay A, Vanlerenberghe J, Adenis L. [The urethane-induced experimental pulmonary adenoma in the mouse. I. Histological study.] CR Seances Soc Biol Fil 1962;156:655–657.

    CAS  Google Scholar 

  43. Mirvish SS. The carcinogenic action and metabolism of urethane and N hydroxyurethane. Adv Cancer Res 1968;11:1–42.

    Article  CAS  PubMed  Google Scholar 

  44. Brooks RE. Pulmonary adenoma of strain A mice: an electron microscopic study. J Natl Cancer Inst 1968;41(3):719–742.

    CAS  PubMed  Google Scholar 

  45. Gargus JL, Paynter OE, Reese WH, Jr. Utilization of newborn mice in the bioassay of chemical carcinogens. Toxicol Appl Pharmacol 1969;15(3):552–559.

    Article  CAS  PubMed  Google Scholar 

  46. Shabad LM. Dose-response studies in experimentally induced lung tumours. Environ Res 1971;4(4):305–315.

    Article  CAS  PubMed  Google Scholar 

  47. Snyder C, Malone B, Nettesheim P, Snyder F. Urethaneinduced pulmonary adenoma as a tool for the study of surfactant biosynthesis. Cancer Res 1973;33(10):2437–2443.

    CAS  PubMed  Google Scholar 

  48. Cazorla M, Hernandez L, Fernandez PL, et al. Ki-ras gene mutations and absence of p53 gene mutations in spontaneous and urethane-induced early lung lesions in CBA/J mice. Mol Carcinog 1998;21(4):251–260.

    Article  CAS  PubMed  Google Scholar 

  49. Lin L, Festing MF, Devereux TR, et al. Additional evidence that the K-ras protooncogene is a candidate for the major mouse pulmonary adenoma susceptibility (Pas-1) gene. Exp Lung Res 1998;24(4):481–497.

    Article  CAS  PubMed  Google Scholar 

  50. Avanzo JL, Mesnil M, Hernandez-Blazquez FJ, et al. Altered expression of connexins in urethane-induced mouse lung adenomas. Life Sci 2006;79(23):2202–8.

    Article  CAS  PubMed  Google Scholar 

  51. Umemura T, Kodama Y, Hioki K, et al. Susceptibility to urethane carcinogenesis of transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice) and its modification by butylhydroxytoluene. Cancer Lett 1999;145(1–2):101–106.

    Article  CAS  PubMed  Google Scholar 

  52. Furth PA. SV40 rodent tumour models as paradigms of human disease: transgenic mouse models. Dev Biol Stand 1998;94:281–287.

    CAS  PubMed  Google Scholar 

  53. Wikenheiser KA, Clark JC, Linnoila RI, et al. Simian virus 40 large T antigen directed by transcriptional elements of the human surfactant protein C gene produces pulmonary adenocarcinomas in transgenic mice. Cancer Res 1992;52(19):5342–5352.

    CAS  PubMed  Google Scholar 

  54. Wikenheiser KA, Whitsett JA. Tumor progression and cellular differentiation of pulmonary adenocarcinomas in SV40 large T antigen transgenic mice. Am J Respir Cell Mol Biol 1997;16(6):713–723.

    CAS  PubMed  Google Scholar 

  55. Kwak I, Tsai SY, DeMayo FJ. Genetically engineered mouse models for lung cancer. Annu Rev Physiol 2004;66:647–663.

    Article  CAS  PubMed  Google Scholar 

  56. Zhao B, Magdaleno S, Chua S, et al. Transgenic mouse models for lung cancer. Exp Lung Res 2000;26(8):567–579.

    Article  CAS  PubMed  Google Scholar 

  57. Albanese C, Hulit J, Sakamaki T, Pestell RG. Recent advances in inducible expression in transgenic mice. Semin Cell Dev Biol 2002;13(2):129–141.

    Article  CAS  PubMed  Google Scholar 

  58. Matsuda I, Aiba A. Receptor knock-out and knock-in strategies. Methods Mol Biol 2004;259:379–390.

    CAS  PubMed  Google Scholar 

  59. Sato Y, Endo H, Ajiki T, et al. Establishment of Cre/LoxP recombination system in transgenic rats. Biochem Biophys Res Commun 2004;319(4):1197–1202.

    Article  CAS  PubMed  Google Scholar 

  60. Altomare DA, Vaslet CA, Skele KL, et al. A mouse model recapitulating molecular features of human mesothelioma. Cancer Res 2005;65(18):8090–8095.

    Article  CAS  PubMed  Google Scholar 

  61. Altomare DA, You H, Xiao GH, et al. Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene 2005;24(40):6080–6089.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY

    Roberto Barrios MD (Professor)

  2. Methodist Hospital, Houston, TX, USA

    Roberto Barrios MD (Professor)

Authors
  1. Roberto Barrios MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pathology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA

    Dani S. Zander MD

  2. Institute of Pathology, Laboratories for Molecular Cytogenetics, Medical University of Graz, Graz, Austria

    Helmut H. Popper MD

  3. Department of Pathology, University of Texas Health Science Center, San Antonio, TX, USA

    Jaishree Jagirdar MD

  4. Weill Medical College of Cornell University, New York, NY

    Abida K. Haque MD

  5. Department of Pathology, San Jacinto Methodist Hospital, Baytown, TX, USA

    Abida K. Haque MD

  6. Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY

    Philip T. Cagle MD  & Roberto Barrios MD  & 

  7. The Methodist Hospital, Houston, TX, USA

    Philip T. Cagle MD  & Roberto Barrios MD  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC.

About this chapter

Cite this chapter

Barrios, R. (2008). Animal Models of Lung Disease. In: Zander, D.S., Popper, H.H., Jagirdar, J., Haque, A.K., Cagle, P.T., Barrios, R. (eds) Molecular Pathology of Lung Diseases. Molecular Pathology Library, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72430-0_14

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-72430-0_14

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-72429-4

  • Online ISBN: 978-0-387-72430-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation