Table 2

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

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]

Igμnull

↑ 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-FcIgG3 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]


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.

Delaleu et al. Arthritis Research & Therapy 2011 13:217   doi:10.1186/ar3313