Langbahn Team – Weltmeisterschaft

NOD mice

Non-obese diabetic or NOD mice, like biobreeding rats, are used as an animal model for type 1 diabetes.[1] Diabetes develops in NOD mice as a result of insulitis, a leukocytic infiltrate of the pancreatic islets.[2] The onset of diabetes is associated with a moderate glycosuria and a non-fasting hyperglycemia. It is recommended to monitor for development of glycosuria from 10 weeks of age; this can be carried out using urine glucose dipsticks. NOD mice will develop spontaneous diabetes when left in a sterile environment.[3] The incidence of spontaneous diabetes in the NOD mouse is 60–80% in females and 20–30% in males. Onset of diabetes also varies between males and females: commonly, onset is delayed in males by several weeks. The mice (as well as C57BL/6 and SJL) are known to carry IgG2c allele.[4][5]

History

Non-obese diabetic (NOD) mice exhibit a susceptibility to spontaneous development of autoimmune insulin dependent diabetes mellitus (IDDM).[6] The NOD strain and related strains were developed at Shionogi Research Laboratories in Aburahi, Japan by Makino and colleagues and first reported in 1980.[7] The group developed the NOD strain by an outbreeding of the cataract-prone strain from JcI:ICR mice.[8]

Susceptibility

The susceptibility to IDDM is polygenic and environment exerts a strong effect on gene penetrances. Environment including housing conditions, health status, and diet all affect development of diabetes in the mice. For instance, NOD mice maintained in different laboratories can have different levels of incidence. The incidence of disease is linked to the microbiome.[9]

NOD mice are also susceptible to developing other autoimmune syndromes, including autoimmunine sialitis, autoimmune thyroiditis, autoimmune peripheral polyneuropathy etc. Diabetes in these mice can be prevented by a single injection of mycobacterial adjuvants such as complete Freund's adjuvant (FCA) or Bacille de Calmette et Guérin (BCG) vaccine.[10][11]

Identifying IDDM susceptibility loci

Genetic Loci associated with susceptibility to IDDM have been identified in the NOD mouse strain through the development of congenic mouse strains, which have identified several insulin dependent diabetes (Idd) loci. The most important is idd1 which is the major histocompatibility complex class II loci I-Ag7.[12]

NOD mice have polymorphisms in the Idd3 locus which are linked to IL-2 production. IL-2 promotes either immunity or tolerance in a concentration dependent fashion by acting on T helper cells, CTL and NK cells. Low amounts of IL-2 may be needed to promote survival of Treg in mice. Loss of IL-2 can thereby contribute to the development of autoimmunity in NOD mice.[13]

NOD mice have a mutation in exon 2 of the CTLA-4 gene, which causes it to be spliced incorrectly. CTLA-4 plays a major role in suppressing the T-cell immune response. Without the proper functioning of CTLA-4, T-cells attack the insulin producing cells. This results in Type 1 Diabetes.[14]

References

  1. ^ "Non-Obese Diabetic (NOD) Mouse BAC Library". National Institute of Allergy and Infectious Diseases. Retrieved 2006-05-15.
  2. ^ Delovitch TL, Singh B (1997). "The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD". Immunity. 7 (6): 727–38. doi:10.1016/s1074-7613(00)80392-1. PMID 9430219.
  3. ^ Eisenbarth GS (2004). "Type 1 diabetes: molecular, cellular and clinical immunology". Adv Exp Med Biol. 552: 306–10. PMID 15622970.
  4. ^ Zhang Z, Goldschmidt T, Salter H (March 2012). "Possible allelic structure of IgG2a and IgG2c in mice". Mol Immunol. 50 (3): 169–71. doi:10.1016/j.molimm.2011.11.006. PMID 22177661.
  5. ^ Fox, James; Anderson, Lynn; Otto, Glen; Corning, Kathleen; Whary, Mark (2015). Laboratory Animal Medicine (3 ed.). Amsterdam: Elsevier Inc (American College of Laboratory Animal Medicine). p. 70. doi:10.1016/B978-0-12-409527-4.00003-1. ISBN 978-0-12-416613-4. OCLC 913513718. S2CID 88753861. ISBN 978-0-12-409527-4.
  6. ^ Kikutani H, Makino S (1992). "The murine autoimmune diabetes model: NOD and related strains". Adv. Immunol. Advances in Immunology. 51: 285–322. doi:10.1016/S0065-2776(08)60490-3. ISBN 9780120224517. PMID 1323922.
  7. ^ Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y (1980). "Breeding of a non-obese, diabetic strain of mice". Jikken Dobutsu. 29 (1): 1–13. doi:10.1538/expanim1978.29.1_1. PMID 6995140.
  8. ^ Leiter, Edward H (1994). "The NOD Mouse: A Model for Analyzing the Interplay Between Heredity and the Environment in the Development of Autoimmune Disease". ILAR Journal. 35 (1): 4–14. doi:10.1093/ilar.35.1.4.
  9. ^ Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV (October 2008). "Innate immunity and intestinal microbiota in the development of Type 1 diabetes". Nature. 455 (7216): 1109–13. doi:10.1038/nature07336. PMC 2574766. PMID 18806780.
  10. ^ Sadelain MW, Qin HY, Lauzon J, Singh B (1990). "Prevention of type I diabetes in NOD mice by adjuvant immunotherapy". Diabetes. 39 (5): 583–9. doi:10.2337/diabetes.39.5.583. PMID 2139617.
  11. ^ Qin HY, Sadelain MW, Hitchon C, Lauzon J, Singh B (1993). "Complete Freund's adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice". J Immunol. 150 (5): 2072–80. doi:10.4049/jimmunol.150.5.2072. PMID 8436836. S2CID 9779509.
  12. ^ Serreze DV, Leiter EH (1994). "Genetic and pathogenic basis of autoimmune diabetes in NOD mice". Curr Opin Immunol. 6 (6): 900–6. doi:10.1016/0952-7915(94)90011-6. PMID 7710714.
  13. ^ Tang Q, Adams JY, Penaranda C, et al. (May 2008). "Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction". Immunity. 28 (5): 687–97. doi:10.1016/j.immuni.2008.03.016. PMC 2394854. PMID 18468463.
  14. ^ Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, et al. (May 2003). "Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease". Nature. 423 (6939): 506–11. doi:10.1038/nature01621. PMID 12724780.
Quelle: https://en.wikipedia.org/wiki/NOD_mice