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Selecting highly sensitive non-obese diabetic mice for improving the study of Sjögren’s syndrome

  • Basic Science
  • Published:
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Abstract

Background

Non-obese diabetic (NOD) mice are a commonly used murine model for the study of Sjögren’s syndrome. However, variations in susceptibility to the disease among the mice has often yielded less stable results. Based on the correlation between the pathological changes and the tear tests, we attempt to establish a simple screening procedure to assure the validity of experimental results by excluding those mice with poor susceptibility to dry eyes.

Methods

Seventy male NOD mice were recruited. The tear film break-up test (BUT) and the phenol red cotton thread test (CTT) were implemented while the mice were under anesthesia. The mice were divided into four groups (grades 1 to 4) based on their BUT readings, and four similar groups based on CTT measurements. Tear samples in each grade were collected for IL-1β detection with ELISA. The lacrimal glands and conjunctiva of the mice were used to detect the levels of leucocyte common antigen (LCA). LCA-Positive staining was considered as the “gold standard” in the receiver operating characteristic curve (ROC curve) analysis. C57BL/6 mice were used as wild-type controls.

Results

There were 13 (18.57%), 43 (61.43%), 10 (14.29%) and 4 (5.71%) mice in grades 1, 2, 3 and 4 by BUT test, and 34 (48.57%), 15 (21.43%), 14 (20.00%) and 7 (10.00%) in grades 1, 2, 3 and 4 by CTT test respectively. Fifty-one out of the 70 mice (72.86%) were detected LCA-positive, and they were mainly in grades 1 and 2 of both the BUT and CCT grading systems. ELISA showed significant variances of IL-β levels among the four groups (p < 0.01), with much lower IL-β levels in group 3 and 4 when both BUT and CTT were used for grouping. The tear IL-β level in the wild-type mice was similar to those of the grade 4 mice, using either BUT or CTT for grouping. The ROC curve analysis provided optimal cutting lines, which were 2 seconds in BUT readings and 4 mm/min in CTT measurements respectively.

Conclusion

BUT and CTT tests are useful methods in screening high susceptible NOD mice. Cutting lines at BUT ≤2 seconds and CTT ≤4 mm/min provide a good balance between the assurance of susceptibility and the maximization of use of NOD mice for the study of Sjögren’s syndrome.

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Authors and Affiliations

  1. Department of Ophthalmology, Huashan Hospital, School of Medicine, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China

    Weibao Xiao & Wen Ye

  2. Laboratory of Clinical Visual Sciences, Institute of the Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai JiaoTong University School of Medicine, 225 South Chongqing Road, Shanghai, 200025, China

    Yalan Wu, Jingfa Zhang & Guo-Tong Xu

  3. Laboratory of Clinical Visual Sciences, Tongji Eye Institute, Shanghai, 200092, China

    Guo-Tong Xu

  4. Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200092, China

    Guo-Tong Xu

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  1. Weibao Xiao
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  2. Yalan Wu
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  3. Jingfa Zhang
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  4. Wen Ye
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Correspondence to Wen Ye or Guo-Tong Xu.

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Xiao, W., Wu, Y., Zhang, J. et al. Selecting highly sensitive non-obese diabetic mice for improving the study of Sjögren’s syndrome. Graefes Arch Clin Exp Ophthalmol 247, 59–66 (2009). https://doi.org/10.1007/s00417-008-0941-1

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  • DOI: https://doi.org/10.1007/s00417-008-0941-1

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