Skip to main content
SpringerLink
Log in

The BB Rat as a Model of Human Type 1 Diabetes

  • Protocol
  • First Online:
Animal Models in Diabetes Research

Part of the book series: Methods in Molecular Biology ((MIMB,volume 933))

Abstract

The BB rat is an important rodent model of human type 1 diabetes (T1D) and has been used to study mechanisms of diabetes pathogenesis as well as to investigate potential intervention therapies for clinical trials. The Diabetes-Prone BB (BBDP) rat spontaneously develops autoimmune T1D between 50 and 90 days of age. The Diabetes-Resistant BB (BBDR) rat has similar diabetes-susceptible genes as the BBDP, but does not become diabetic in viral antibody-free conditions. However, the BBDR rat can be induced to develop T1D in response to certain treatments such as regulatory T cell (Treg) depletion, toll-like receptor ligation, or virus infection. These diabetes-inducible rats develop hyperglycemia under well-controlled circumstances and within a short, predictable time frame (14–21 days), thus facilitating their utility for investigations of specific stages of diabetes development. Therefore, these rat strains are invaluable models for studying autoimmune diabetes and the role of environmental factors in its development, of particular importance due to the influx of studies associating virus infection and human T1D.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
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 159.00
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

Institutional subscriptions

References

  1. Like AA, Guberski DL, Butler L (1991) Influence of environmental viral agents on frequency and tempo of diabetes mellitus in BB/Wor rats. Diabetes 40:259–262

    Article  PubMed  CAS  Google Scholar 

  2. Colle E (1990) Genetic susceptibility to the development of spontaneous insulin-dependent diabetes mellitus in the rat. Clin Immunol Immunopathol 57:1–9

    Article  PubMed  CAS  Google Scholar 

  3. Fuks A, Ono SJ, Colle E et al (1990) A single dose of the MHC-linked susceptibility determinant associated with the RT1u haplotype is permissive for insulin-dependent diabetes mellitus in the BB rat. Exp Clin Immunogenet 7:162–169

    PubMed  CAS  Google Scholar 

  4. Mordes JP, Bortell R, Blankenhorn EP et al (2004) Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR J 45:278–291

    PubMed  CAS  Google Scholar 

  5. Elder ME, Maclaren NK (1983) Identification of profound peripheral T lymphocyte immunodeficiencies in the spontaneously diabetic BB rat. J Immunol 130:1723–1731

    PubMed  CAS  Google Scholar 

  6. Ramanathan S, Poussier P (2001) BB rat lyp mutation and type 1 diabetes. Immunol Rev 184:161–171

    Article  PubMed  CAS  Google Scholar 

  7. Yale JF, Grose M, Marliss EB (1985) Time course of the lymphopenia in BB rats. Relation to the onset of diabetes. Diabetes 34:955–959

    Article  PubMed  CAS  Google Scholar 

  8. Awata T, Guberski DL, Like AA (1995) Genetics of the BB rat: association of autoimmune disorders (diabetes, insulitis, and thyroiditis) with lymphopenia and major histocompatibility complex class II. Endocrinology 136:5731–5735

    Article  PubMed  CAS  Google Scholar 

  9. Shin JH, Janer M, McNeney B et al (2007) IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5. Genes Immun 8:503–512

    Article  PubMed  CAS  Google Scholar 

  10. Hellquist A, Zucchelli M, Kivinen K et al (2007) The human GIMAP5 gene has a common polyadenylation polymorphism increasing risk to systemic lupus erythematosus. J Med Genet 44:314–321

    Article  PubMed  CAS  Google Scholar 

  11. Hornum L, Romer J, Markholst H (2002) The diabetes-prone BB rat carries a frameshift mutation in Ian4, a positional candidate of Iddm1. Diabetes 51:1972–1979

    Article  PubMed  CAS  Google Scholar 

  12. MacMurray AJ, Moralejo DH, Kwitek AE et al (2002) Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene. Genome Res 12:1029–1039

    Article  PubMed  CAS  Google Scholar 

  13. Wong VW, Saunders AE, Hutchings A et al (2010) The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein. Self Nonself 1:259–268

    PubMed  Google Scholar 

  14. Keita M, Leblanc C, Andrews D et al (2007) GIMAP5 regulates mitochondrial integrity from a distinct subcellular compartment. Biochem Biophys Res Commun 361:481–486

    Article  PubMed  CAS  Google Scholar 

  15. Sandal T, Aumo L, Hedin L et al (2003) Irod/Ian5: an inhibitor of gamma-radiation- and okadaic acid-induced apoptosis. Mol Biol Cell 14:3292–3304

    Article  PubMed  CAS  Google Scholar 

  16. Pandarpurkar M, Wilson-Fritch L, Corvera S et al (2003) Ian4 is required for mitochondrial integrity and T cell survival. Proc Natl Acad Sci U S A 100:10382–10387

    Article  PubMed  CAS  Google Scholar 

  17. Pino SC, O’Sullivan-Murphy B, Lidstone EA et al (2009) CHOP mediates endoplasmic reticulum stress-induced apoptosis in Gimap5-deficient T cells. PLoS One 4:e5468

    Article  PubMed  Google Scholar 

  18. Trudeau JD, Dutz JP, Arany E et al (2000) Neonatal beta-cell apoptosis: a trigger for autoimmune diabetes? Diabetes 49:1–7

    Article  PubMed  CAS  Google Scholar 

  19. Kolb H, Worz-Pagenstert U, Kleemann R et al (1996) Cytokine gene expression in the BB rat pancreas: natural course and impact of bacterial vaccines. Diabetologia 39:1448–1454

    Article  PubMed  CAS  Google Scholar 

  20. Zipris D (1996) Evidence that Th1 lymphocytes predominate in islet inflammation and thyroiditis in the BioBreeding (BB) rat. J Autoimmun 9:315–319

    Article  PubMed  CAS  Google Scholar 

  21. Hanenberg H, Kolb-Bachofen V, Kantwerk-Funke G et al (1989) Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of pre-diabetic BB rats. Diabetologia 32:126–134

    Article  PubMed  CAS  Google Scholar 

  22. Jackson RA, Eisenbarth GS (1983) Type I diabetes of man and the BB rat: monoclonal antibody-defined T-cell abnormalities. Diagn Immunol 1:240–244

    PubMed  CAS  Google Scholar 

  23. Marliss EB, Nakhooda AF, Poussier P et al (1982) The diabetic syndrome of the ‘BB’ Wistar rat: possible relevance to type 1 (insulin-dependent) diabetes in man. Diabetologia 22:225–232

    Article  PubMed  CAS  Google Scholar 

  24. Woda BA, Like AA, Padden C et al (1986) Deficiency of phenotypic cytotoxic-suppressor T lymphocytes in the BB/W rat. J Immunol 136:856–859

    PubMed  CAS  Google Scholar 

  25. Ramanathan S, Norwich K, Poussier P (1998) Antigen activation rescues recent thymic emigrants from programmed cell death in the BB rat. J Immunol 160:5757–5764

    PubMed  CAS  Google Scholar 

  26. Greiner DL, Handler ES, Nakano K et al (1986) Absence of the RT-6 T cell subset in diabetes-prone BB/W rats. J Immunol 136:148–151

    PubMed  CAS  Google Scholar 

  27. Bortell R, Kanaitsuka T, Stevens LA et al (1999) The RT6 (Art2) family of ADP-ribosyltransferases in rat and mouse. Mol Cell Biochem 193:61–68

    Article  PubMed  CAS  Google Scholar 

  28. Bortell R, Waite DJ, Whalen BJ et al (2001) Levels of Art2+ cells but not soluble Art2 protein correlate with expression of autoimmune diabetes in the BB rat. Autoimmunity 33:199–211

    Article  Google Scholar 

  29. Gold DP, Bellgrau D (1991) Identification of a limited T-cell receptor beta chain variable region repertoire associated with diabetes in the BB rat. Proc Natl Acad Sci U S A 88:9888–9891

    Article  PubMed  CAS  Google Scholar 

  30. Sommandas V, Rutledge EA, Van Yserloo B et al (2005) Aberrancies in the differentiation and maturation of dendritic cells from bone-marrow precursors are linked to various genes on chromosome 4 and other chromosomes of the BB-DP rat. J Autoimmun 25:1–12

    Article  PubMed  CAS  Google Scholar 

  31. Sommandas V, Rutledge EA, Van Yserloo B et al (2005) Defects in differentiation of bone-marrow derived dendritic cells of the BB rat are partly associated with IDDM2 (the lyp gene) and partly associated with other genes in the BB rat background. J Autoimmun 25:46–56

    Article  PubMed  CAS  Google Scholar 

  32. Todd DJ, Forsberg EM, Greiner DL et al (2004) Deficiencies in gut NK cell number and function precede diabetes onset in BB rats. J Immunol 172:5356–5362

    PubMed  CAS  Google Scholar 

  33. Whalen BJ, Mordes JP, Rossini AA (2001) The BB rat as a model of human insulin-dependent diabetes mellitus. Curr Protoc Immunol Chapter 15:Unit 15.13

    Google Scholar 

  34. Lefebvre DE, Powell KL, Strom A et al (2006) Dietary proteins as environmental modifiers of type 1 diabetes mellitus. Annu Rev Nutr 26:175–202

    Article  PubMed  CAS  Google Scholar 

  35. Wang GS, Kauri LM, Patrick C et al (2010) Enhanced islet expansion by beta-cell proliferation in young diabetes-prone rats fed a protective diet. J Cell Physiol 224:501–508

    Article  PubMed  CAS  Google Scholar 

  36. Olson DE, Paveglio SA, Huey PU et al (2003) Glucose-responsive hepatic insulin gene therapy of spontaneously diabetic BB/Wor rats. Hum Gene Ther 14:1401–1413

    Article  PubMed  CAS  Google Scholar 

  37. Posselt AM, Barker CF, Friedman AL et al (1992) Prevention of autoimmune diabetes in the BB rat by intrathymic islet transplantation at birth. Science 256:1321–1324

    Article  PubMed  CAS  Google Scholar 

  38. Burstein D, Mordes JP, Greiner DL et al (1989) Prevention of diabetes in BB/Wor rat by single transfusion of spleen cells. Parameters that affect degree of protection. Diabetes 38:24–30

    Article  PubMed  CAS  Google Scholar 

  39. Rossini AA, Mordes JP, Pelletier AM et al (1983) Transfusions of whole blood prevent spontaneous diabetes mellitus in the BB/W rat. Science 219:975–977

    Article  PubMed  CAS  Google Scholar 

  40. Ramanathan S, Poussier P (1999) T cell reconstitution of BB/W rats after the initiation of insulitis precipitates the onset of diabetes. J Immunol 162:5134–5142

    PubMed  CAS  Google Scholar 

  41. Laupacis A, Stiller CR, Gardell C et al (1983) Cyclosporin prevents diabetes in BB Wistar rats. Lancet 1:10–12

    Article  PubMed  CAS  Google Scholar 

  42. Like AA, Anthony M, Guberski DL et al (1983) Spontaneous diabetes mellitus in the BB/W rat. Effects of glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes. Diabetes 32:326–330

    Article  PubMed  CAS  Google Scholar 

  43. Dugoni WE Jr, Bartlett ST (1990) Evidence that cyclosporine prevents rejection and recurrent diabetes in pancreatic transplants in the BB rat. Transplantation 49:845–848

    Article  PubMed  CAS  Google Scholar 

  44. Tori M, Ito T, Yumiba T et al (1999) Significant role of intragraft lymphoid tissues in preventing insulin-dependent diabetes mellitus recurrence in whole pancreaticoduodenal transplantation. Microsurgery 19:338–343

    Article  PubMed  CAS  Google Scholar 

  45. Kover KL, Geng Z, Hess DM et al (2000) Anti-CD154 (CD40L) prevents recurrence of diabetes in islet isografts in the DR-BB rat. Diabetes 49:1666–1670

    Article  PubMed  CAS  Google Scholar 

  46. Beaudette-Zlatanova BC, Whalen B, Zipris D et al (2006) Costimulation and autoimmune diabetes in BB rats. Am J Transplant 6:894–902

    Article  PubMed  CAS  Google Scholar 

  47. van den Brandt J, Fischer HJ, Walter L et al (2010) Type 1 diabetes in BioBreeding rats is critically linked to an imbalance between Th17 and regulatory T cells and an altered TCR repertoire. J Immunol 185:2285–2294

    Article  PubMed  Google Scholar 

  48. Castano L, Eisenbarth GS (1990) Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol 8:647–679

    Article  PubMed  CAS  Google Scholar 

  49. Horn GT, Bugawan TL, Long CM et al (1988) Allelic sequence variation of the HLA-DQ loci: relationship to serology and to insulin-dependent diabetes susceptibility. Proc Natl Acad Sci U S A 85:6012–6016

    Article  PubMed  CAS  Google Scholar 

  50. Couper JJ, Steele C, Beresford S et al (1999) Lack of association between duration of breast-feeding or introduction of cow’s milk and development of islet autoimmunity. Diabetes 48:2145–2149

    Article  PubMed  CAS  Google Scholar 

  51. Norris JM, Barriga K, Klingensmith G et al (2003) Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 290:1713–1720

    Article  PubMed  CAS  Google Scholar 

  52. Hviid A, Stellfeld M, Wohlfahrt J et al (2004) Childhood vaccination and type 1 diabetes. N Engl J Med 350:1398–1404

    Article  PubMed  CAS  Google Scholar 

  53. Helgason T, Jonasson MR (1981) Evidence for a food additive as a cause of ketosis-prone diabetes. Lancet 2:716–720

    Article  PubMed  CAS  Google Scholar 

  54. Pietropaolo M, Trucco M (1996) Viral elements in autoimmunity of type I diabetes. Trends Endocrinol Metab 7:139–144

    Article  PubMed  CAS  Google Scholar 

  55. Yoon JW, Jun HS (2004) Viruses in type 1 diabetes: brief review. ILAR J 45:343–348

    PubMed  CAS  Google Scholar 

  56. Laron Z (2002) Interplay between heredity and environment in the recent explosion of type 1 childhood diabetes mellitus. Am J Med Genet 115:4–7

    Article  PubMed  Google Scholar 

  57. Bortell R, Pino SC, Greiner DL et al (2008) Closing the circle between the bedside and the bench: toll-like receptors in models of virally induced diabetes. Ann N Y Acad Sci 1150:112–122

    Article  PubMed  CAS  Google Scholar 

  58. Yeung WC, Rawlinson WD, Craig ME (2011) Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ 342:d35

    Article  PubMed  Google Scholar 

  59. Atkinson MA, Leiter EH (1999) The NOD mouse model of type 1 diabetes: as good as it gets? Nat Med 5:601–604

    Article  PubMed  CAS  Google Scholar 

  60. Seung E, Iwakoshi N, Woda BA et al (2000) Allogeneic hematopoietic chimerism in mice treated with sublethal myeloablation and anti-CD154 antibody: absence of graft-versus-host disease, induction of skin allograft tolerance, and prevention of recurrent autoimmunity in islet-allografted NOD/Lt mice. Blood 95:2175–2182

    PubMed  CAS  Google Scholar 

  61. Gerling IC, Friedman H, Greiner DL et al (1994) Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes. Diabetes 43:433–440

    Article  PubMed  CAS  Google Scholar 

  62. Kruger AJ, Yang C, Lipson KL et al (2011) Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats. Autoimmunity 44:137–148

    Article  PubMed  CAS  Google Scholar 

  63. Greiner DL, Mordes JP, Handler ES et al (1987) Depletion of RT6.1+ T lymphocytes induces diabetes in resistant biobreeding/Worcester (BB/W) rats. J Exp Med 166:461–475

    Article  PubMed  CAS  Google Scholar 

  64. Kukreja A, Cost G, Marker J et al (2002) Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest 109:131–140

    PubMed  CAS  Google Scholar 

  65. Brusko TM, Wasserfall CH, Clare-Salzler MJ et al (2005) Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes. Diabetes 54:1407–1414

    Article  PubMed  CAS  Google Scholar 

  66. Thomas VA, Woda BA, Handler ES et al (1991) Altered expression of diabetes in BB/Wor rats by exposure to viral pathogens. Diabetes 40:255–258

    Article  PubMed  CAS  Google Scholar 

  67. Doukas J, Cutler AH, Mordes JP (1994) Polyinosinic:polycytidylic acid is a potent activator of endothelial cells. Am J Pathol 145:137–147

    PubMed  CAS  Google Scholar 

  68. Sobel DO, Goyal D, Ahvazi B et al (1998) Low dose poly I:C prevents diabetes in the diabetes prone BB rat. J Autoimmun 11:343–352

    Article  PubMed  CAS  Google Scholar 

  69. Ewel CH, Sobel DO, Zeligs BJ et al (1992) Poly I:C accelerates development of diabetes mellitus in diabetes-prone BB rat. Diabetes 41:1016–1021

    Article  PubMed  CAS  Google Scholar 

  70. Sobel DO, Azumi N, Creswell K et al (1995) The role of NK cell activity in the pathogenesis of poly I:C accelerated and spontaneous diabetes in the diabetes prone BB rat. J Autoimmun 8:843–857

    Article  PubMed  CAS  Google Scholar 

  71. Alexopoulou L, Holt AC, Medzhitov R et al (2001) Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature 413:732–738

    Article  PubMed  CAS  Google Scholar 

  72. Guberski DL, Thomas VA, Shek WR et al (1991) Induction of type I diabetes by Kilham’s rat virus in diabetes-resistant BB/Wor rats. Science 254:1010–1013

    Article  PubMed  CAS  Google Scholar 

  73. Kruger AJ, Yang C, Tam SW et al (2010) Haptoglobin as an early serum biomarker of virus-induced autoimmune type 1 diabetes in biobreeding diabetes resistant and LEW1.WR1 rats. Exp Biol Med (Maywood) 235:1328–1337

    Article  CAS  Google Scholar 

  74. Zipris D, Lien E, Xie JX et al (2005) TLR activation synergizes with Kilham rat virus infection to induce diabetes in BBDR rats. J Immunol 174:131–142

    PubMed  CAS  Google Scholar 

  75. McKisic MD, Paturzo FX, Gaertner DJ et al (1995) A nonlethal rat parvovirus infection suppresses rat T lymphocyte effector functions. J Immunol 155:3979–3986

    PubMed  CAS  Google Scholar 

  76. Ellerman KE, Richards CA, Guberski DL et al (1996) Kilham rat triggers T-cell-dependent autoimmune diabetes in multiple strains of rat. Diabetes 45:557–562

    Article  PubMed  CAS  Google Scholar 

  77. Zipris D, Hillebrands JL, Welsh RM et al (2003) Infections that induce autoimmune diabetes in BBDR rats modulate CD4  +  CD25+ T cell populations. J Immunol 170:3592–3602

    PubMed  CAS  Google Scholar 

  78. Chung YH, Jun HS, Kang Y et al (1997) Role of macrophages and macrophage-derived cytokines in the pathogenesis of Kilham rat virus-induced autoimmune diabetes in diabetes-resistant BioBreeding rats. J Immunol 159:466–471

    PubMed  CAS  Google Scholar 

  79. Chung YH, Jun HS, Son M et al (2000) Cellular and molecular mechanism for Kilham rat virus-induced autoimmune diabetes in DR-BB rats. J Immunol 165:2866–2876

    PubMed  CAS  Google Scholar 

  80. Nair A, Wolter TR, Meyers AJ et al (2008) Innate immune pathways in virus-induced autoimmune diabetes. Ann N Y Acad Sci 1150:139–142

    Article  PubMed  CAS  Google Scholar 

  81. Zipris D, Lien E, Nair A et al (2007) TLR9-signaling pathways are involved in Kilham rat virus-induced autoimmune diabetes in the biobreeding diabetes-resistant rat. J Immunol 178:693–701

    PubMed  CAS  Google Scholar 

  82. Wolter TR, Wong R, Sarkar SA et al (2009) DNA microarray analysis for the identification of innate immune pathways implicated in virus-induced autoimmune diabetes. Clin Immunol 132:103–115

    Article  PubMed  CAS  Google Scholar 

  83. Heinig M, Petretto E, Wallace C et al (2010) A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. Nature 467:460–464

    Article  PubMed  CAS  Google Scholar 

  84. Yoon JW, Jun HS (2006) Viruses cause type 1 diabetes in animals. Ann N Y Acad Sci 1079:138–146

    Article  PubMed  Google Scholar 

  85. Chen S, Howard O (2004) Images in clinical medicine. Parvovirus B19 infection. N Engl J Med 350:598

    Article  PubMed  CAS  Google Scholar 

  86. Munakata Y, Kodera T, Saito T et al (2005) Rheumatoid arthritis, type 1 diabetes, and Graves’ disease after acute parvovirus B19 infection. Lancet 366:780

    Article  PubMed  Google Scholar 

  87. Mordes JP, Guberski DL, Leif JH et al (2005) LEW.1WR1 rats develop autoimmune diabetes spontaneously and in response to environmental perturbation. Diabetes 54:2727–2733

    Article  PubMed  CAS  Google Scholar 

  88. Kaldunski M, Jia S, Geoffrey R et al (2010) Identification of a serum-induced transcriptional signature associated with type 1 diabetes in the BioBreeding rat. Diabetes 59:2375–2385

    Article  PubMed  CAS  Google Scholar 

  89. Wang X, Jia S, Geoffrey R et al (2008) Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics. J Immunol 180:1929–1937

    PubMed  CAS  Google Scholar 

  90. Gottlieb PA, Handler ES, Appel MC et al (1991) Insulin treatment prevents diabetes mellitus but not thyroiditis in RT6-depleted diabetes resistant BB/Wor rats. Diabetologia 34:296–300

    Article  PubMed  CAS  Google Scholar 

  91. Lefkowith J, Schreiner G, Cormier J et al (1990) Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes. J Exp Med 171:729–743

    Article  PubMed  CAS  Google Scholar 

  92. Mendez I, Chung YH, Jun HS et al (2004) Immunoregulatory role of nitric oxide in Kilham rat virus-induced autoimmune diabetes in DR-BB rats. J Immunol 173:1327–1335

    PubMed  CAS  Google Scholar 

  93. Ugrasbul F, Moore WV, Tong PY et al (2008) Prevention of diabetes: effect of mycophenolate mofetil and anti-CD25 on onset of diabetes in the DRBB rat. Pediatr Diabetes 9:596–601

    Article  PubMed  CAS  Google Scholar 

  94. Popovic J, Kover KL, Moore WV (2004) The effect of immunomodulators on prevention of autoimmune diabetes is stage dependent: FTY720 prevents diabetes at three different stages in the diabetes-resistant biobreeding rat. Pediatr Diabetes 5:3–9

    Article  PubMed  Google Scholar 

  95. Jorns A, Rath KJ, Terbish T et al (2010) Diabetes prevention by immunomodulatory FTY720 treatment in the LEW.1AR1-iddm rat despite immune cell activation. Endocrinology 151:3555–3565

    Article  PubMed  Google Scholar 

  96. Peschke E, Hofmann K, Bahr I et al (2011) The insulin-melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus). Diabetologia 54:1831–1840

    Article  PubMed  CAS  Google Scholar 

  97. Mordes JP, Cort L, Norowski E et al (2009) Analysis of the rat Iddm14 diabetes susceptibility locus in multiple rat strains: identification of a susceptibility haplotype in the Tcrb-V locus. Mamm Genome 20:162–169

    Article  PubMed  CAS  Google Scholar 

  98. Bottazzo GF (1986) Lawrence lecture. Death of a beta cell: homicide or suicide? Diabet Med 3:119–130

    Article  PubMed  CAS  Google Scholar 

  99. Atkinson MA, Bluestone JA, Eisenbarth GS et al (2011) How does type 1 diabetes develop?: the notion of homicide or beta-cell suicide revisited. Diabetes 60:1370–1379

    Article  PubMed  CAS  Google Scholar 

  100. Lipson KL, Fonseca SG, Urano F (2006) Endoplasmic reticulum stress-induced apoptosis and auto-immunity in diabetes. Curr Mol Med 6:71–77

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH grants AI073871 and DK352520, and grants from the Brehm Foundation and the Juvenile Diabetes Research Foundation.

Author information

Authors and Affiliations

  1. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Rita Bortell & Chaoxing Yang

Authors
  1. Rita Bortell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chaoxing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rita Bortell .

Editor information

Editors and Affiliations

  1. , Department of Pharmacology, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany

    Hans-Georg Joost

  2. German Diabetes Centre, Clinical Biochemistry &Pathobiochemistry, Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, Düsseldorf, 40225, Germany

    Hadi Al-Hasani

  3. , Department of Experimental Diabetology, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany

    Annette Schürmann

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Bortell, R., Yang, C. (2012). The BB Rat as a Model of Human Type 1 Diabetes. In: Joost, HG., Al-Hasani, H., Schürmann, A. (eds) Animal Models in Diabetes Research. Methods in Molecular Biology, vol 933. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-068-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-068-7_3

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-067-0

  • Online ISBN: 978-1-62703-068-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation