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Table 2 Alterations in disease phenotype observed in association with genetic modification and experimental intervention

From: Sjögren's syndrome: studying the disease in mice

Strain/modification/intervention SS-like phenotypea Remarksa Reference
(NZB/NZW)F1 SG and LG infl. SLE-like disease [19]
   IFA    ↑ SG infl., ↓ SG function, anti-Ro    ↑ DC numbers early in the disease process [22]
   Anti-CD25    ↑ SG infl., anti-Ro    ↑ ANA [23]
   Poly(I:C)    ↓ SG function (transient)    Role of TLR3 engagement [24]
NOD SG and LG infl., ↓ SG and LG function T1D, multiple immune system-related alterations [12]
    scid    No SG infl., ↑ SG function    Abnormal salivary gland physiology remains [60]
    Igμ null    ↑ SG function    Insulitis but no progression to overt T1D [64]
    ll4-/-    ↑ SG function    Absence of anti-M3R IgG1 [77]
    Ifnγ-/-    No SG infl., ↑ SG function, ↑ LG infl.    Retained LG infl. [78]
    IfnγR-/-    No SG infl., ↑ SG function, ↑ LG infl.    Retained LG infl. [78]
   Tnfr1-FcIgG 3 Tg    ↓ SG and LG infl.    Insulitis but no progression to overt T1D [75]
    Ica69-/-    ↓ SG and LG infl.    Unchanged incidence rate of T1D [61]
    Aire-/-    ↑ LG infl., ↓ LG function    Role of OBP1a and central tolerance [63]
   NZW-Ssial3    ↓ SG infl., SG function unchanged    Unchanged insulitis score [55]
    E2f1-/-    ↑ SG infl., ↓ SG function    ↑ T1D, ↓ Tregs [58]
Hsp60    ↓ SG infl., ↑ SG function    Biomarkers in saliva predict treatment success [57]
Hsp60 amino acids 437 to 460    ↓ SG infl., ↑ SG function    Biomarkers in saliva indicate SG function [57]
LTβR-Ig    Arrested progression of SG infl.    Changes in cellular composition of SG infl. [48]
Anti-VCAM1    ↓ LG infl.    LG function, SG infl. and SG function not assessed [76]
Anti-α4-integrin    ↓ LG infl.    LG function, SG infl. and SG function not assessed [76]
Anti-PNAd    ↓ LG infl.    LG function, SG infl. and SG function not assessed [76]
Anti-L-selectin    ↓ LG infl.    LG function, SG infl. and SG function not assessed [76]
Anti-LFA1    ↓ LG infl.    LG function, SG infl. and SG function not assessed [76]
Il10    ↓ SG infl., ↑ SG function    Retrograde gene delivery through SG ducts [96]
Tnfr1-Ig    ↓ SG function    Retrograde gene delivery through SG ducts [74]
NOD-H2b SG and LG infl., ↓ SG and LG function No T1D [42]
    ll4-/-    ↑ SG function    Absence of anti-M3R IgG1 [65]
   C.Stat6-/-    ↑ SG function    Absence of anti-M3R IgG1 [66]
NOD-scid No SG infl., normal SG function Abnormal salivary gland physiology remains [60]
    Ifnγ-/-    No SG and LG infl., ↑ SG function    Improved salivary gland physiology [78]
    E2f1-/-    No SG infl., retained ↓ SG function    Effect of E2F1 deficiency on SG development [59]
C57BL/6.NOD-Aec1Aec2 SG and LG infl. ↓ SG and LG function Increased applicability compared with NOD mice [41]
    C3-/-    No SG and LG infl., ↑ SG function    Assessing the role of C3 [88]
Il17r:Fc    ↓ SG infl., ↑ SG function    Retrograde gene delivery through SG ducts [81]
C57BL/6 May develop SG infl. at an old age Widely used recipient strain  
Il17a    SG infl., ↓ SG function    Retrograde gene delivery through SG ducts [80]
C57BL/6-Il14α Tg SG infl., ↓ SG function High incidence of CD5+ lymphoma, nephritis [101]
    Ltα -/-    ↓ SG infl., ↑ SG function    LTα-dependent disease phenotype [104]
C57BL/6-Id3-/- SG and LG infl., ↓ SG function, anti-Ro and La Exocrine gland dysfunction precedes SG and LG infl. [125]
Anti-CD20    ↓ SG and LG infl., ↑ SG function    Depletion of B cells [127]
C57BL/6-Baff Tg SG and LG infl., ↓ SG function MZ B-cell dominated infl., SLE-like disease [106]
    Ltβ-/-    ↓ SG infl., ↑ SG function    MZ B-cell dependence of the SS-like disease [107]
    Tnfα-/-    Unchanged    Increased incidence of B-cell lymphoma [110]
BALB/c-Act1-/- SG and LG infl., anti-Ro and anti-La MZ B-cell dominated infl., SLE-like disease [115]
    CD40-/-    SG and LG infl. unchanged    Absence of anti-Ro and anti-La [115]
  1. Selection of genetic modifications and specific intervention, which gave insight into the mechanisms underlying either the etiology or the pathogenesis of Sjögren's syndrome (SS)-like disease in the original strain. ↑, increased; ↓, decreased; AIRE, autoimmune regulator; ANA, antinuclear antibodies; DC, dendritic cells; E2F1, E2F transcription factor 1; HSP, heat shock protein; IFA, Freund's incomplete adjuvant; infl., inflammation; LFA, leukocyte function-associated antigen; LG, lacrimal gland; LT, lymphotoxin; M3R, muscarinic acetylcholine type-3 receptor; MZ, marginal zone; NOD, nonobese diabetic mice; OBP1a, odorant binding protein 1a; PNAd, peripheral node addressin; poly(I:C), polyinosinic:polycytidylic acid; scid, severe combined immunodeficiency; SG, salivary gland; SLE, systemic lupus erythematosus; STAT, signal transducer and activator of transcription; T1D, type 1 diabetes; Tg, transgenic; TLR, Toll-like receptor; Treg, regulatory T cell; VCAM, vascular cell adhesion molecule. aFor all modified strains and interventions, listings refer to relative changes compared with the original, not indented, strain listed above.