Table 2.
Spontaneous mouse models of Sjögren’s Syndrome. Summary of the characteristics, autoantibodies, genetics, and pathogenesis reported in each mouse model.
| Spontaneous Mouse Model | Characteristics | Autoantibodies | Genetics & Pathogenesis | References |
|---|---|---|---|---|
| NOD Mice | - Lymphocytic infiltration of lacrimal, salivary glands and pancreas leading to sialadenitis, dry eye and xerostomia, insulitis and β-islet destruction | - anti-SSA/Ro, anti-SSB/La and anti-muscarinic receptor III | - Insulin-dependent diabetes loci 3 and 5 | 25–33 |
| NOD.B10.H2b Mice | - Lymphocytic infiltration of lacrimal, salivary glands | - dsDNA, ssDNA, and U1-snRNP68 in female mice | - MHC I–Ag7Idd1 susceptibility locus is replaced by the MHC I-Ab locus from C57BL/10 mice | 32,34,35 |
| C57BL/6.NODAec1Aec2 Mice | - Lymphocytic infiltration of salivary glands with decreased salivary flow rate - Dacryoadenitisin males only |
- ANAs - IgM against mM3R-transfected Flp-In CHO cell |
- Aec2 and Aec1 on chromosomes 1 and 3, respectively | 36 |
| NOD.IFN-γ−/− & NOD.IFN-γ R−/− Mice |
- No salivary function loss - Lymphocytic infiltration - Increase in acinar cells apoptosis, or abnormal salivary protein expression by 20 weeks of age |
- IFN-γ | 37 | |
| NOD.IL4−/− Mice | - Lymphocyte infiltration started at week 8 and was more severe at 20 weeks compared to NOD mice | - Absence of M3R autoantibodies | - IL-4 | 38 |
| NOD Igμ−/- Mice | - Salivary and lacrimal gland T cell infiltration at 8 weeks and normal salivary function | - Higher cysteine protease activity in acinar and ductal cells | 39 | |
| NZB/W F1 Mice | - Lymphocyte infiltration of lacrimal and salivary glands at week 16; more severe in lacrimal glands of old female mice | - Absence of autoantibodies, anti–SS–A and anti–SS–B | 40, 41 | |
| MRL/lpr Mice | - A complex of SLE, SS, and RA-like disease. - Lymphocyte infiltration of lacrimal and salivary glands - Submandibular gland is more affected than parotid and sublingual glands |
- Controversial reports of anti-SSA/Ro or anti SSB/La - Absence of anti–SS–A and anti–SS–B |
- IL-1β and TNF-α before and IL-6 after lesion appearance | 41, 42 |
| NFS/s1d Mice | - Spontaneous inflammatory change in the salivary and lacrimal glands in thymectomised mice 3 days after birth. - Females show more severe inflammation. |
- Anti-salivary duct autoantibodies - A 120-kDa autoantigen α-fodrin |
- Lymphocytic infiltration with CD3+ and CD4+ T cells with some CD8+ T cells and B220 B cells - Upregulated IL-1 beta, TNF-α, IL-2, IFN-γ, IL-6, IL-10, IL-12p40, and adhesion molecules, ICAM-1, LFA-1, CD44, Mel-14. |
45–47 |
| Aly/aly Mice | - Mononuclear cell infiltrate; mainly of CD4+ T cells infiltrate periductal areas of salivary and lacrimal glands, pancreas and lungs | - Mononuclear cell infiltrate; mainly of CD4+ T cells | 48 | |
| IQI/Jic Mice | - Lymphocyte infiltration in salivary and lacrimal glands starting at 4 weeks. - 80% of females at all ages showed sialadenitis that worsened after 6 months of age. Females show more severe symptoms compared to males. - At 8 weeks, B cells and CD4+ T cells infiltrate salivary and lacrimal glands, lungs, pancreas and kidneys. |
- MHC II+, CD11c+ and B7-2+ dendritic cells - CD4+ CD25+ Treg cells |
49–53 |