Alleles from chromosomes 1 and 3 of NOD mice combine to influence Sjögren's syndrome-like autoimmune exocrinopathy

J Rheumatol. 2000 Aug;27(8):1896-904.


Objective: NOD mice exhibit at least 2 overlapping autoimmune diseases: autoimmune endocrinopathy (Type I, insulin dependent diabetes) and autoimmune exocrinopathy (Sjogren's syndrome, SS). To date, 18 chromosomal regions have been identified that contribute to development of diabetes in NOD mice; however, genetic mapping of similar susceptibility loci for autoimmune exocrinopathy is just beginning. We investigated if these 2 autoimmune diseases share a genetic predisposition.

Methods: Congenic partner strains of NOD and C57BL/6 mice containing defined genetic intervals influencing susceptibility to diabetes (Idd) were screened for histological and biochemical markers for their effect on the development of SS-like disease. Saliva flow rates, protein concentration, amylase activity, and cysteine protease activity were evaluated.

Results: In contrast to the nonsusceptible parental C57BL/6 strain, C57BL/6.NOD Idd5 congenic partner strain, containing a genetic region derived from chromosome 1 of the NOD mouse, exhibited pathophysiological characteristics of autoimmune exocrinopathy. Replacement of individual diabetes susceptibility intervals Idd3, Idd5, Idd13, Idd1, and Idd9, as well as a combination of the Idd3, Idd10, and Idd17 intervals, with resistance alleles had little effect on development of autoimmune exocrinopathy. Conversely, NOD mice, in which the chromosome regions containing both Idd5 and Idd3 have been replaced by intervals derived from C57BL mice, exhibit a reduced pathophysiology associated with SS-like autoimmune exocrinopathy.

Conclusion: Alleles on chromosomes 1 (Idd5) and 3 (Idd3) in combination appear to greatly influence susceptibility and resistance to development of autoimmune exocrinopathy. The association with certain Idd, but not other Idd loci, indicate that genetic overlap is present but probably not inclusive.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles*
  • Amylases / metabolism
  • Animals
  • Chromosomes*
  • Cysteine Endopeptidases / metabolism
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / enzymology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / pathology
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Saliva / enzymology
  • Saliva / metabolism
  • Sjogren's Syndrome / complications
  • Sjogren's Syndrome / enzymology
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / pathology
  • Submandibular Gland / metabolism
  • Submandibular Gland / pathology


  • Amylases
  • Cysteine Endopeptidases