Table 1.

Summary of Primary SjS Animal Models

Strain	Strain Background	Sjőgren syndrome-like disease									Remarks	References

		Infiltration			Secretory dysfunction			Autoantibodies
		SG	LG	Other	Saliva	Tear	Onset (weeks)	SSA	SSB	Other
NOD^*	ICR	Y	Y	T1D	Y	Y	12–16	Y	Y	ANA Anti-M3R T1D Ags	T1D model Prominent dacryoadenitis in males & sialadenitis in females	[45, 52–54, 56–58]

*NOD derivatives*

NOD.B10-H2^b	NOD C57BL/10	Y	Y	No T1D	Y	Y	12–16	Y	Y	ANA Anti-M3R	First pSjS model No T1D or insulitis Diabetogenic MHC replaced with H2^b of C57BL/10	[59–64, 67]
C57BL/6. NOD-Aec1Aec2	C57BL/6.NODc3 C57BL/6.NODc1t	Y	Y	No T1D	Y	Y	8–10	Y	Y	ANA Anti-M3R	pSjS in C56BL/6 background Easy to compare with C57BL/6 Lacrymal gland dysfunction only in males	[54, 58, 70, 73, 76, 78, 79, 173]
NOD.IFN-γ^−/−	NOD/Lt	N	Y	No T1D	N	ND	Normal secretion	ND	ND	No ANA No anti-M3R	Lack of autoimmune responses No abnormal glandular homeostasis w/o IFN-γ Infiltration in LG of males	[84]
NOD.Igμ^−/−	NOD/Lt	Y	Y	No T1D	N	N	Normal Secretion	ND	ND	ND	No functional B-cells Infusion of purified serum IgG or F(ab′)2 from NOD inducing secretory dysfunction	[85]
NOD.IL4^−/−	NOD/Lt	Y	Y	No T1D	N	N	Normal secretion	ND	ND	ANA Anti-M3R	Impact of Th2 response on secretory dysfunction Absence of IgG1 anti-M3R ab.	[86]

*Other spontaneous models*

NFS/sld^**	NFS/N	Y	Y	No other organs	Y	ND	18–20 months	Y	Y	Anti-α-fodrin &-salivary duct	Proteolysis of α-fodrin Infiltration starting at 4 weeks Secretion compared with younger mice at 18–20 months	[87–91, 93, 94]
IQI/Jic	ICR	Y	Y	pancreas kidney lungs	ND	ND	ND	N	N	ANA	Sialadenitis at 6 months Dacryoadenitis at 9 months IgG ANA by 15 months	[103–109]
Aly/aly	C57BL/6xAEJ ( H-2b)	Y	Y	liver pancreas lungs	ND	ND	ND	N	N	No ANA	Homozygous autosomal recessive mutation in aly gene	[113, 114, 118]

*Transgenic and knockout mice*

Id3 KO	129/SV-C57BL/6	Y	Y	No other organs	Y	Y	8	Y	Y	ND	Id3 germline KO strain Anti-SSA or -SSB antibodies present after 1 year of age Infiltration after 8 weeks	[119, 120, 125]
Id3^f/f;LckCre	129/SV-C57BL/6	Y	ND	No other organs	Y	ND	ND	N	N	ND	T cell lineage-specific Id3 conditional KO strain	[123]
PI3K KO ( r1ΔT/r2n)	129Sv-C57BL/6-FVB	Y	Y	lungs liver intestines	Y	Y	< 8	Y	Y	ANA	Inflammatory lesions in multiple organs Aberrant T_H cell differentiation	[132]
Ar KO	C57BL/6J/129	Y	ND	kidney	ND	ND	ND	ND	ND	No ANA Anti-α-fodrin	Absence of estrogen due to aromatase gene inactivation Occasional renal failures Infiltration at 12–17 months	[138–141]
RbAp48 Tg	C57BL/6	Y	Y	ND	Y	Y	30	Y	Y	ND	Absence of estrogen Prominent expression of RbAp48	[134, 143, 144]

*Induced models*

Ro immunization	Balb/c and others	Y	ND	ND	Y	N	16	Y	Y	ANA partly	Ro peptide immunization by intraperitoneal injection to Balb/c mice	[152–154, 156, 157]
M3R immunization	C57BL/6 129/SV-C57BL/6	Y	ND	ND	Y	ND	2	ND	ND	Anti-M3R	Adoptive transfer of splenocytes from M3R^−/− mice (immunized with M3R peptides) into Rag^−/− immunodeficient mice	[150, 151]
	NOD/LtJ	W	W	ND	ND	ND	ND	ND	ND	ND	Young female NOD/LtJ immunized with a M3R peptide corresponding to the second extracellular loop of M3R	[158]
CAII immunization	PL/J(H-2^u)	Y	Y	pancreas kidney	ND	ND	ND	ND	ND	ND	Lymphocytic foci & atrophy of surrounding SG acinar cells	[162, 163]

Secondary SjS mouse model;

^**

Only if thymectomized

SG, salivary glands; LG, lacrimal glands; ND, not determined; T1D, type I diabetes; pSjS, primary Sjögren’s syndrome; Saialadenitis, infiltration in the salivary glands; Dacryoadenitis, infiltration in the lacrimal glands; W, weak (improved) infiltration