Phenotypes associated with this allele

• Allele Symbol: Fas^lpr
• Allele Name: lymphoproliferation
• Allele ID: MGI:1856334
• Summary: 86 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fas^lpr/Fas^lpr	AK.MRL-Fas^lpr	MGI:3799204
hm2	Fas^lpr/Fas^lpr	B6.Cg-Apoe^tm1Unc Fas^lpr	MGI:3800214
hm3	Fas^lpr/Fas^lpr	B6.MRL-Fas^lpr	MGI:3798887
hm4	Fas^lpr/Fas^lpr	B6.MRL-Fas^lpr/J	MGI:3707398
hm5	Fas^lpr/Fas^lpr	C3.MRL-Fas^lpr	MGI:3799268
hm6	Fas^lpr/Fas^lpr	C3.MRL-Fas^lpr/J	MGI:3796615
hm7	Fas^lpr/Fas^lpr	involves: 129P2/OlaHsd * MRL	MGI:4944221
hm8	Fas^lpr/Fas^lpr	involves: C3H * MRL/Mp	MGI:3694733
hm9	Fas^lpr/Fas^lpr	involves: C57BL/6 * MRL/Mp	MGI:4361837
hm10	Fas^lpr/Fas^lpr	involves: MRL/Mp	MGI:3851804
hm11	Fas^lpr/Fas^lpr	MRL.Cg-Irf1^tm1Mak Fas^lpr	MGI:3769145
hm12	Fas^lpr/Fas^lpr	MRL.Cg-Tnfrsf9^tm1Byk Fas^lpr	MGI:3800241
hm13	Fas^lpr/Fas^lpr	MRL-Fas^lpr	MGI:3761609
hm14	Fas^lpr/Fas^lpr	MRL/Mp-Agtpbp1^atms Fas^lpr	MGI:3613077
hm15	Fas^lpr/Fas^lpr	MRL/Mp-Fas^lpr	MGI:2450135
hm16	Fas^lpr/Fas^lpr	MRL/MpJ-Fas^lpr	MGI:3799686
hm17	Fas^lpr/Fas^lpr	MRL/MpJ-Fas^lpr/J	MGI:3639605
hm18	Fas^lpr/Fas^lpr	NOD.MRL(B6)-Fas^lpr	MGI:3622771
hm19	Fas^lpr/Fas^lpr	NOD.MRL-Fas^lpr	MGI:3663022
ht20	Fas^lpr/Fas^tm1.1Cgn	involves: C57BL/6 * MRL	MGI:3690618
cn21	Fas^lpr/Fas^lpr Hspa13^tm1.1Smoc/Hspa13^tm1.1Smoc Cd19^tm1(cre)Cgn/Cd19^+	involves: 129P2/OlaHsd * 129S * C57BL/6 * MRL/Mp	MGI:6694199
cn22	Cd19^tm1(cre)Cgn/Cd19^+ Fas^lpr/Fas^tm1Cgn Tg(Cd4-cre)1Cwi/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2 * MRL	MGI:3690553
cn23	Cd19^tm1(cre)Cgn/Cd19^+ Fas^lpr/Fas^tm1Cgn	involves: 129P2/OlaHsd * C57BL/6 * MRL	MGI:3690552
cn24	Fas^lpr/Fas^tm1Cgn Tg(Cd4-cre)1Cwi/0	involves: C57BL/6 * DBA/2 * MRL	MGI:3690551
cx25	Apoe^tm1Unc/Apoe^tm1Unc Fas^lpr/Fas^lpr	B6.Cg-Apoe^tm1Unc Fas^lpr	MGI:3800213
cx26	Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast Fas^lpr/Fas^lpr	B6.Cg-Bcl2l11^tm1.1Ast Fas^lpr	MGI:3800656
cx27	Fas^lpr/Fas^lpr Havcr1^tm1Kuch/Havcr1^tm1Kuch	B6.Cg-Havcr1^tm1Kuch Fas^lpr	MGI:5437713
cx28	Fas^lpr/Fas^lpr Il2ra^tm1Dw/Il2ra^tm1Dw Tg(CD2-Ccdc86)1Hfuj/?	B6.Cg-Il2ra^tm1Dw Fas^lpr Tg(CD2-Ccdc86)1Hfuj	MGI:4356291
cx29	Fas^lpr/Fas^lpr Tlr9^tm1Aki/Tlr9^tm1Aki	B6.Cg-Tlr9^tm1Aki Fas^lpr	MGI:3799744
cx30	Dsg4^hage/Dsg4^hage Fas^lpr/Fas^lpr X/Yaa	EOD-Dsg4^hage	MGI:3812133
cx31	Fas^lpr/Fas^lpr Fasl^tm2.1Bksa/Fasl^tm2.1Bksa	involves: 129 * C57BL/6 * MRL/Mp	MGI:5006703
cx32	Fas^lpr/Fas^lpr Tcra^tm1Mjo/Tcra^tm1Mjo	involves: 129P2/OlaHsd * 129S2/SvPas * MRL	MGI:4947940
cx33	Cd40lg^tm1Flv/Y Fas^lpr/Fas^lpr	involves: 129P2/OlaHsd * 129S2/SvPas * MRL	MGI:4947942
cx34	Cd40lg^tm1Flv/Y Fas^lpr/Fas^lpr Tcra^tm1Mjo/Tcra^tm1Mjo	involves: 129P2/OlaHsd * 129S2/SvPas * MRL	MGI:4947943
cx35	Cd40lg^tm1Flv/Cd40lg^tm1Flv Fas^lpr/Fas^lpr	involves: 129P2/OlaHsd * 129S2/SvPas * MRL	MGI:4947941
cx36	Cd40lg^tm1Flv/Cd40lg^tm1Flv Fas^lpr/Fas^lpr Tcra^tm1Mjo/Tcra^tm1Mjo	involves: 129P2/OlaHsd * 129S2/SvPas * MRL	MGI:4947944
cx37	Fas^lpr/Fas^lpr Il4^tm1Cgn/Il4^tm1Cgn	involves: 129P2/OlaHsd * C57BL/6J * MRL/Mp	MGI:4839051
cx38	Fas^lpr/Fas^lpr Pou2af1^tm1Pmt/Pou2af1^tm1Pmt	involves: 129P2/OlaHsd * C57BL/6 * MRL	MGI:3800140
cx39	Fas^lpr/Fas^lpr Tcra^tm1Mjo/Tcra^tm1Mjo	involves: 129P2/OlaHsd * MRL	MGI:4944220
cx40	Fas^lpr/Fas^lpr Tlr7^tm1Flv/Y	involves: 129S1/Sv * C57BL/6 * MRL/Mp	MGI:5478501
cx41	Fas^lpr/Fas^lpr Ighm^tm1Cgn/Ighm^tm1Cgn	involves: 129S2/SvPas * C57BL/6 * MRL/Mp	MGI:3767451
cx42	Dntt^tm1Gfn/Dntt^tm1Gfn Fas^lpr/Fas^lpr	involves: 129S2/SvPas * C57BL/6 * MRL/MpJ	MGI:3640320
cx43	C3^tm1Crr/C3^tm1Crr Fas^lpr/Fas^lpr	involves: 129S4/SvJae * C57BL/6 * MRL	MGI:3800669
cx44	C4b^tm1Crr/C4b^tm1Crr Fas^lpr/Fas^lpr	involves: 129S4/SvJae * C57BL/6 * MRL	MGI:3800668
cx45	C3^tm1Crr/C3^tm1Crr C4b^tm1Crr/C4b^tm1Crr Fas^lpr/Fas^lpr	involves: 129S4/SvJae * C57BL/6 * MRL	MGI:3800670
cx46	Fas^lpr/Fas^lpr Itfg2^Gt(OST215121)Lex/Itfg2^Gt(OST215121)Lex	involves: 129S5/SvEvBrd * C57BL/6J * MRL/Mp	MGI:5552962
cx47	Fas^lpr/Fas^lpr Spp1^tm1Rit/Spp1^tm1Rit	involves: 129S7/SvEvBrd * C57BL/6 * MRL/Mp	MGI:4361838
cx48	Fas^lpr/Fas^lpr Ifng^tm1Ts/Ifng^tm1Ts	involves: 129S7/SvEvBrd * DBA/1 * MRL/Mp	MGI:4839049
cx49	Fas^lpr/Fas^lpr Nos2^tm1Mrl/Nos2^tm1Mrl	involves: 129S7/SvEvBrd * MRL	MGI:4837859
cx50	Fas^lpr/Fas^lpr Tnfrsf1a^tm1.1Gkl/Tnfrsf1a^tm1.1Gkl	involves: 129/Sv * C57BL/6	MGI:3053737
cx51	Fas^lpr/Fas^lpr Raf1^tm1Bacc/Raf1^tm1Bacc	involves: 129/SvHsd * 129P2/OlaHsd * C57BL/6 * MRL	MGI:3799535
cx52	Fas^lpr/Fas^+ Raf1^tm1Bacc/Raf1^+	involves: 129/SvHsd * 129P2/OlaHsd * C57BL/6 * MRL	MGI:3799536
cx53	Fas^lpr/Fas^+ Raf1^tm1Bacc/Raf1^tm1Bacc	involves: 129/SvHsd * 129P2/OlaHsd * C57BL/6 * MRL	MGI:3799534
cx54	Cd72^b/Cd72^b Fas^lpr/Fas^lpr	involves: C57BL/6 * C57BL/6JJmsSlc * MRL/Mp	MGI:5563354
cx55	Cd72^c/Cd72^c Fas^lpr/Fas^lpr	involves: C57BL/6 * C57BL/6JJmsSlc * MRL/Mp	MGI:5563353
cx56	Fas^lpr/Fas^lpr Tg(H2-K-Cd86)27All/0	involves: C57BL/6 * CBA * MRL/MpJ	MGI:3662636
cx57	Cd72^tm1Tsub/Cd72^tm1Tsub Fas^lpr/Fas^lpr	involves: C57BL/6J * C57BL/6JJmsSlc * MRL/Mp	MGI:5563351
cx58	Fas^lpr/Fas^lpr Kdelr1^m1Btlr/Kdelr1^m1Btlr	involves: C57BL/6J * MRL/Mp	MGI:5689998
cx59	Fas^lpr/Fas^+ Tg(TcraTcrb)1100Mjb/?	involves: C57BL/6 * MRL/Mp	MGI:5292731
cx60	Apoe^tm1Unc/Apoe^tm1Unc Fas^lpr/Fas^lpr	MRL.Cg-Apoe^tm1Unc Fas^lpr	MGI:3799494
cx61	Ccr2^tm1Blck/Ccr2^tm1Blck Fas^lpr/Fas^lpr	MRL.Cg-Ccr2^tm1Blck Fas^lpr	MGI:3665495
cx62	Cd180^tm1Kmiy/Cd180^tm1Kmiy Fas^lpr/Fas^lpr	MRL.Cg-Cd180^tm1Kmiy Fas^lpr	MGI:3799683
cx63	Ebi3^tm1Nkma/Ebi3^tm1Nkma Fas^lpr/Fas^lpr	MRL.Cg-Ebi3^tm1Nkma Fas^lpr	MGI:5312683
cx64	Fas^lpr/Fas^lpr Igh-J^tm2(3H9-VDJ*)Mwg/Igh-J^+	MRL.Cg-Fas^lpr Igh-J^tm2(3H9-VDJ*)Mwg	MGI:3809239
cx65	Fas^lpr/Fas^lpr Tg(CD2-Foxj1)#Stlp/0	MRL.Cg-Fas^lpr Tg(CD2-Foxj1)#Stlp	MGI:3800459
cx66	Fas^lpr/Fas^lpr Fcer1g^tm1Tks/Fcer1g^tm1Tks	MRL.Cg-Fcer1g^tm1Tks Fas^lpr	MGI:4360203
cx67	Fas^lpr/Fas^lpr Ifnar1^tm1Agt/Ifnar1^tm1Agt	MRL.Cg-Ifnar1^tm1Agt Fas^lpr	MGI:4838774
cx68	Fas^lpr/Fas^lpr Ifngr1^tm1Agt/Ifngr1^tm1Agt	MRL.Cg-Ifngr1^tm1Agt Fas^lpr	MGI:4838777
cx69	Fas^lpr/Fas^lpr Ifnar1^tm1Agt/Ifnar1^tm1Agt Ifngr1^tm1Agt/Ifngr1^tm1Agt	MRL.Cg-Ifngr1^tm1Agt Ifnar1^tm1Agt Fas^lpr	MGI:4838775
cx70	Fas^lpr/Fas^lpr Ifng^tm1Ts/Ifng^+	MRL.Cg-Ifng^tm1Ts Fas^lpr	MGI:3801419
cx71	Fas^lpr/Fas^lpr Ifng^tm1Ts/Ifng^tm1Ts	MRL.Cg-Ifng^tm1Ts Fas^lpr	MGI:3801418
cx72	Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra^tm1Mak	MRL.Cg-Il27ra^tm1Mak Fas^lpr	MGI:4943704
cx73	Fas^lpr/Fas^lpr Il4^tm1Cgn/Il4^tm1Cgn	MRL.Cg-Il4^tm1Cgn Fas^lpr	MGI:3799736
cx74	Fas^lpr/Fas^lpr Irf1^tm1Mak/Irf1^tm1Mak	MRL.Cg-Irf1^tm1Mak Fas^lpr	MGI:3769143
cx75	Fas^lpr/Fas^lpr Irf1^tm1Mak/Irf1^+	MRL.Cg-Irf1^tm1Mak Fas^lpr	MGI:3769144
cx76	Fas^lpr/Fas^lpr Selplg^tm1Fur/Selplg^tm1Fur	MRL.Cg-Selplg^tm1Fur Fas^lpr	MGI:3800806
cx77	Fas^lpr/Fas^lpr Selp^tm1Bay/Selp^tm1Bay	MRL.Cg-Selp^tm1Bay Fas^lpr	MGI:3799723
cx78	Fas^lpr/Fas^lpr Tcra^tm1Mjo/Tcra^+	MRL.Cg-Tcra^tm1Mjo Fas^lpr	MGI:4944218
cx79	Fas^lpr/Fas^lpr Tlr9^tm1Aki/Tlr9^tm1Aki	MRL.Cg-Tlr9^tm1Aki Fas^lpr	MGI:5478500
cx80	Fas^lpr/Fas^lpr Tnfrsf13c^Bcmd1/Tnfrsf13c^+	MRL.Cg-Tnfrsf13c^Bcmd1 Fas^lpr	MGI:3800181
cx81	Fas^lpr/Fas^lpr Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk	MRL.Cg-Tnfrsf9^tm1Byk Fas^lpr	MGI:3800222
cx82	Agtpbp1^atms/Agtpbp1^atms Fas^lpr/Fas^lpr	MRL/Mp-Agtpbp1^atms Fas^lpr	MGI:3613073
cx83	Agtpbp1^atms/Agtpbp1^atms Fas^lpr/?	MRL/Mp-Agtpbp1^atms Fas^lpr	MGI:3613075
cx84	Fas^lpr/Fas^lpr Sh2d1a^rpl/Sh2d1a^rpl	MRL/Mp-Fas^lpr Sh2d1a^rpl	MGI:3761613
cx85	Fas^lpr/Fas^lpr Tg(Ins2-Fasl)24Ach/0	NOD.Cg-Fas^lpr Tg(Ins2-Fasl)24Ach	MGI:3663021
cx86	Fas^lpr/Fas^lpr Tg(INS-Il10)#Sar/0	NOD.Cg-Fas^lpr Tg(INS-Il10)#Sar	MGI:3622770

Genotype
MGI:3799204

hm1

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: AK.MRL-Fas^lpr

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

increased immunoglobulin level ( J:7454 )

• IgG and IgM levels are modestly increased in serum at 6 months

enlarged lymph nodes ( J:7454 )

• nodes are 6 times normal size

increased autoantibody level ( J:7454 )

• increase in thymocytotoxic autoantibodies at 6 months is seen

increased anti-nuclear antigen antibody level ( J:7454 )

• mice have significantly increased levels of anti-ssDNA antibodies

increased anti-double stranded DNA antibody level ( J:7454 )

• antibodies are increased relative to controls

glomerulonephritis ( J:7454 )

• Background Sensitivity: immune complex glomerulonephritis develops by 1 year of age but is much milder than in MRL homozygotes

renal/urinary system

abnormal renal glomerulus morphology ( J:7454 )

• nephritic changes consist of focal increase in mesangial substance and mild mesangial proliferation

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

glomerulonephritis ( J:7454 )

• Background Sensitivity: immune complex glomerulonephritis develops by 1 year of age but is much milder than in MRL homozygotes

expanded mesangial matrix ( J:7454 )

• focal increase in mesangial substance

renal glomerular immunoglobulin deposits ( J:7454 )

hematopoietic system

increased immunoglobulin level ( J:7454 )

• IgG and IgM levels are modestly increased in serum at 6 months

cardiovascular system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

cellular

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

Genotype
MGI:3800214

hm2

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: B6.Cg-Apoe^tm1Unc Fas^lpr

cardiovascular system

cardiovascular system phenotype ( J:121671 )

N • at 5 months, mice show no atherosclerotic lesions in the aorta when on a normal chow diet or after 5 weeks of a high-fat diet

Genotype
MGI:3798887

hm3

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: B6.MRL-Fas^lpr

mortality/aging

premature death ( J:6638 , J:7454 , J:135036 )

• median survival is 284 days, compared to 795 days for controls (J:6638)

• 50% mortality is observed at 13.5 months with 90% mortality at 16 months, significantly reduced from wild-type (J:7454)

• 64% survival at 24 weeks (J:135036)

immune system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

enlarged spleen ( J:135036 )

increased double-negative T cell number ( J:135036 )

increased immunoglobulin level ( J:7454 )

• IgG and IgM levels are increased in serum at 6 months

enlarged lymph nodes ( J:6638 , J:7454 , J:135036 )

• by 4 months of age, lymph nodes are increased 10- to 20-fold (J:6638)

• nodes are 13 times normal size (J:7454)

• generalized lymphadenopathy (J:135036)

decreased interleukin-2 secretion ( J:6638 )

• defect in Il2 activity begins during early life and worsens with age; spleen cells show no stimulated Il2 production upon stimulation with concanavalin A

increased autoantibody level ( J:7454 , J:135036 )

• increase in thymocytotoxic autoantibodies at 6 months is seen (J:7454)

• mice have elevated levels of anti-chromatin antibodies compared to double mutants (J:135036)

increased anti-nuclear antigen antibody level ( J:6638 , J:135036 )

• anti-nuclear antibodies are present at 6 months of age (J:6638)

• mice have elevated levels of anti-chromatin (anti-nucleosome) antibodies compared to double mutants (J:135036)

increased anti-double stranded DNA antibody level ( J:7454 )

• antibodies are increased relative to controls

glomerulonephritis ( J:7454 , J:135036 )

• Background Sensitivity: immune complex glomerulonephritis develops by 1 year of age but is much milder than in MRL homozygotes (J:7454)

• interstitial lymphoid infiltration is observed at 6 months; glomerular IgG deposits that are exclusively mesangial are observed (J:135036)

renal/urinary system

abnormal renal glomerulus morphology ( J:7454 )

• nephritic changes consist of focal increase in mesangial substance and mild mesangial proliferation

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

glomerulonephritis ( J:7454 , J:135036 )

• Background Sensitivity: immune complex glomerulonephritis develops by 1 year of age but is much milder than in MRL homozygotes (J:7454)

• interstitial lymphoid infiltration is observed at 6 months; glomerular IgG deposits that are exclusively mesangial are observed (J:135036)

expanded mesangial matrix ( J:7454 )

• focal increase in mesangial substance

renal glomerular immunoglobulin deposits ( J:7454 , J:135036 )

hematopoietic system

enlarged spleen ( J:135036 )

increased double-negative T cell number ( J:135036 )

increased immunoglobulin level ( J:7454 )

• IgG and IgM levels are increased in serum at 6 months

cardiovascular system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

cellular

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

growth/size/body

enlarged spleen ( J:135036 )

Genotype
MGI:3707398

hm4

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: B6.MRL-Fas^lpr/J

immune system

decreased B cell apoptosis ( J:135830 )

• after bile duct ligation (BDL), Peyer's patch B cells do not display evidence of apoptosis

increased immature B cell number ( J:132217 )

• plasmablast numbers in spleen are increased relative to wild-type

increased transitional stage B cell number ( J:132217 )

• higher numbers of T2 B cells in spleen relative to wild-type

increased follicular B cell number ( J:132217 )

• higher in spleen relative to wild-type

increased marginal zone B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

abnormal splenic cell ratio ( J:132217 )

• T1:follicular B cell ratio is higher than wild-type or Bcl2l11-deficient mice

increased splenocyte number ( J:132217 )

• total number of CD19+ splenocytes is higher than wild-type

• total number of splenocytes is increased relative to wild-type

abnormal NK cell physiology ( J:115033 )

• continuous treatment with recombinant murine IL12 results in sustained recruitment of NK cells to the liver

enlarged lymph nodes ( J:119584 )

• mice develop less severe lymphadenopathy at later ages than the double mutant Igh-6/Fas mice

lymph node hyperplasia ( J:132217 )

• total number of cells per lymph node is increased compared to wild-type

increased autoantibody level ( J:132217 )

• total anti-IgM antibody levels are increased compared to wild-type

increased anti-nuclear antigen antibody level ( J:132217 )

• anti-nuclear antibodies are increased compared to wild-type

increased anti-double stranded DNA antibody level ( J:132217 )

• anti-ssDNA IgM and IgG antibodies are increased compared to wild-type

increased anti-histone antibody level ( J:132217 )

• increased compared to wild-type

increased anti-single stranded DNA antibody level ( J:132217 )

• anti-ssDNA IgM and IgG antibodies are increased compared to wild-type

CNS inflammation ( J:120427 )

brain inflammation ( J:120427 )

• by 7 days after TMEV infection, inflammation is present, decreasing slightly by 21 days, but widespread tissue damage is present, similar to controls (B6)

• tissue damage is less frequent at 45 days than in Prf-null mice

increased susceptibility to bacterial infection ( J:136745 )

• mice infected with 500 CFU of S. aureus have drastically elevated number of S. aureus CFU compared to similarly-infected wild-type mice, but lower counts than infected Fasl^gld mice

increased susceptibility to Picornaviridae infection ( J:120427 )

• inflammation and tissue damage in the brain are slightly greater than in control, resistant mice at 45 and 180 days

hematopoietic system

decreased B cell apoptosis ( J:135830 )

• after bile duct ligation (BDL), Peyer's patch B cells do not display evidence of apoptosis

increased immature B cell number ( J:132217 )

• plasmablast numbers in spleen are increased relative to wild-type

increased transitional stage B cell number ( J:132217 )

• higher numbers of T2 B cells in spleen relative to wild-type

increased follicular B cell number ( J:132217 )

• higher in spleen relative to wild-type

increased marginal zone B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

abnormal splenic cell ratio ( J:132217 )

• T1:follicular B cell ratio is higher than wild-type or Bcl2l11-deficient mice

increased splenocyte number ( J:132217 )

• total number of CD19+ splenocytes is higher than wild-type

• total number of splenocytes is increased relative to wild-type

abnormal NK cell physiology ( J:115033 )

• continuous treatment with recombinant murine IL12 results in sustained recruitment of NK cells to the liver

renal/urinary system

increased renal glomerulus apoptosis ( J:132217 )

• higher numbers of apoptotic cells are detected in glomeruli compared to wild-type

abnormal kidney morphology ( J:132217 )

• number of macrophages surrounding glomeruli is increased compared to wild-type which have no macrophage index

abnormal renal glomerulus basement membrane morphology ( J:132217 )

• IgG deposits mainly localized to glomerular basement membrane are increased relative to wild-type

liver/biliary system

focal hepatic necrosis ( J:135830 )

• necroinflammatory foci after BDL are reduced in number compared to controls

abnormal hepatocyte morphology ( J:135830 )

• confluent foci of feathery hepatocyte degeneration due to bile acid cytotoxicity are significantly reduced compared to controls hours after BDL

abnormal liver physiology ( J:120559 , J:135830 )

• when mice are recipients of wild-type hepatitis B surface antigen (HBsAg)-specific Th1 cells after treatment with HBsAg, severe liver injury is induced to similar extent as in wild-type mice (J:120559)

• treatment with Prf1-deficient HBsAg-specific Th1 cells and HBsAg induces liver injury as severe as that induced by wild-type HBsAg-specific Th1 cells (J:120559)

• after BDL, necroinflammatory foci and lymphocytic infiltration are obviously less than in controls (J:135830)

decreased hepatocyte apoptosis ( J:135830 )

• hepatocyte cell death is reduced compared to controls after BDL

nervous system

CNS inflammation ( J:120427 )

brain inflammation ( J:120427 )

• by 7 days after TMEV infection, inflammation is present, decreasing slightly by 21 days, but widespread tissue damage is present, similar to controls (B6)

• tissue damage is less frequent at 45 days than in Prf-null mice

demyelination ( J:120427 )

• by 7 days after TMEV infection, inflammation is present in the meninges and gray matter of spinal cord, but decreases by 21 days, although not as much as in controls (B6)

cellular

decreased B cell apoptosis ( J:135830 )

• after bile duct ligation (BDL), Peyer's patch B cells do not display evidence of apoptosis

increased renal glomerulus apoptosis ( J:132217 )

• higher numbers of apoptotic cells are detected in glomeruli compared to wild-type

decreased hepatocyte apoptosis ( J:135830 )

• hepatocyte cell death is reduced compared to controls after BDL

focal hepatic necrosis ( J:135830 )

• necroinflammatory foci after BDL are reduced in number compared to controls

Genotype
MGI:3799268

hm5

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: C3.MRL-Fas^lpr

homeostasis/metabolism

abnormal interleukin level ( J:8267 )

• stimulation with concanavalin A does not induce cells to produce Il2

immune system

salivary gland inflammation ( J:1028 )

lacrimal gland inflammation ( J:1028 )

• at 2 months, glandular inflammation is neglible; at 5 months, nearly all mice exhibit lacrimal gland inflammation covering a larger area than in mutants at 2 months or controls at 5 months

• inflammation correlates with age, immune complex level and spleen weight; antinuclear antibody level correlation is greater than probability cutoff; controls do not show correlations with these factors and gland inflammation

• inflammatory infiltrates consist of mononuclear cells and occurs in a periductal or perivascular pattern

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

abnormal T cell morphology ( J:8267 )

• lymph node cells (T cell origin) are abnormal; cells are Ly-2^-/L3T4^-/surface Ig^-

abnormal T cell physiology ( J:8267 )

• cells do not generate CTL in response to stimulation with alloantigens

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

abnormal interleukin level ( J:8267 )

• stimulation with concanavalin A does not induce cells to produce Il2

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:1028 )

N • submandibular gland inflammation is observed in most mice at 5 months, but differences compared to wild-type are not significant

N • no parotid gland inflammation is observed and only 1 animal showed sublingual gland inflammation at 5 months

N • in inflamed lacrimal glands, lobular boundaries are preserved with preservation of interlobular septae; lobular atrophy occurs with preservation of ductal epithelium; widely dilated ducts indicate that ductal obstruction is not observed

salivary gland inflammation ( J:1028 )

lacrimal gland atrophy ( J:1028 )

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

lacrimal gland inflammation ( J:1028 )

• at 2 months, glandular inflammation is neglible; at 5 months, nearly all mice exhibit lacrimal gland inflammation covering a larger area than in mutants at 2 months or controls at 5 months

• inflammation correlates with age, immune complex level and spleen weight; antinuclear antibody level correlation is greater than probability cutoff; controls do not show correlations with these factors and gland inflammation

• inflammatory infiltrates consist of mononuclear cells and occurs in a periductal or perivascular pattern

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

hematopoietic system

abnormal T cell morphology ( J:8267 )

• lymph node cells (T cell origin) are abnormal; cells are Ly-2^-/L3T4^-/surface Ig^-

abnormal T cell physiology ( J:8267 )

• cells do not generate CTL in response to stimulation with alloantigens

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

vision/eye

lacrimal gland atrophy ( J:1028 )

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

lacrimal gland inflammation ( J:1028 )

• at 2 months, glandular inflammation is neglible; at 5 months, nearly all mice exhibit lacrimal gland inflammation covering a larger area than in mutants at 2 months or controls at 5 months

• inflammation correlates with age, immune complex level and spleen weight; antinuclear antibody level correlation is greater than probability cutoff; controls do not show correlations with these factors and gland inflammation

• inflammatory infiltrates consist of mononuclear cells and occurs in a periductal or perivascular pattern

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

digestive/alimentary system

salivary gland inflammation ( J:1028 )

cellular

decreased apoptosis ( J:114219 )

• unlike wild-type vaginal cells, vaginal cells derived from mutant mice do not undergo apoptosis after treatment with agonistic anti-mouse Fas antibody or mouse recombinant TNF antibody

decreased neuron apoptosis ( J:124252 )

• neuron viability is comparable to wild-type when grown in absence of Abeta or if treated with KCN which induces necrotic cell death

• very low levels of apoptosis (15%) compared to wild-type (60%) are seen when cortical neurons are treated with Abeta25-35 or Abeta1-40 peptides

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

nervous system

decreased neuron apoptosis ( J:124252 )

• neuron viability is comparable to wild-type when grown in absence of Abeta or if treated with KCN which induces necrotic cell death

• very low levels of apoptosis (15%) compared to wild-type (60%) are seen when cortical neurons are treated with Abeta25-35 or Abeta1-40 peptides

reproductive system

abnormal vagina weight ( J:114219 )

♀ • at 2 days after estrogen deprivation induced by gonadectomy, mutant females show no vaginal regression (measured by a decrease in vaginal organ weight), indicating no Fas-mediated vaginal cell death, in contrast to wild-type females that show >50% decrease in vaginal organ weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:1028

Genotype
MGI:3796615

hm6

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: C3.MRL-Fas^lpr/J

cardiovascular system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

mortality/aging

mortality/aging ( J:120650 )

N • when placed under hyperoxic conditions for >5 days, mice do not show increased survival (resistance to hyperoxia) compared to wild-type mice

premature death ( J:7454 )

• 50% mortality is observed at 11.5 months with 90% mortality at 14 months, significantly reduced from wild-type

hematopoietic system

decreased eosinophil cell number ( J:106288 )

• airway eosinophils are decreased with anti-Il5 teatment compared to contol IgG-teated animals at 96 hours

abnormal T cell morphology ( J:7454 )

• (sIg^-, Ly-5(B220⁺) are present at 4 weeks of age in spleen and by 16-20 weeks, represent 80% of cells

abnormal B cell activation ( J:7454 )

• after 10 weeks of age, there is a 2-fold increase in frequency of immunoglobulin-containing and secreting cells in the spleen; this does not occur until abnormal T cells (Ly-5(B220⁺) cells) are found in the spleen

increased immunoglobulin level ( J:7454 )

• IgG and IgM levels are increased in serum at 6 months

immune system

immune system phenotype ( J:7454 )

N • mice show normal spleen and lymph node cell cytotoxic T cell response to alloantigen

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

decreased eosinophil cell number ( J:106288 )

• airway eosinophils are decreased with anti-Il5 teatment compared to contol IgG-teated animals at 96 hours

abnormal T cell morphology ( J:7454 )

• (sIg^-, Ly-5(B220⁺) are present at 4 weeks of age in spleen and by 16-20 weeks, represent 80% of cells

abnormal B cell activation ( J:7454 )

• after 10 weeks of age, there is a 2-fold increase in frequency of immunoglobulin-containing and secreting cells in the spleen; this does not occur until abnormal T cells (Ly-5(B220⁺) cells) are found in the spleen

increased immunoglobulin level ( J:7454 )

• IgG and IgM levels are increased in serum at 6 months

enlarged lymph nodes ( J:7454 )

• nodes are 29 times normal size

lymph node hyperplasia ( J:7454 )

• after 10 weeks of age, there is a 3- to 4-fold increase in numbers of B lymphocytes, and after 6 weeks of age, there is a 4- to 5-fold increase in number of null cells (sIg^-, Thy-1^-)

decreased interleukin-2 secretion ( J:7454 )

• after 6 weeks of age, spleen cells show significant decrease in ability to produce Il-2 induced by concanavalin A treatment

increased autoantibody level ( J:7454 )

• marked increase in thymocytotoxic autoantibodies at 6 months is seen

increased anti-nuclear antigen antibody level ( J:7454 )

• mice have significantly increased levels of anti-ssDNA antibodies

increased anti-double stranded DNA antibody level ( J:7454 )

• antibodies are increased relative to controls

glomerulonephritis ( J:7454 )

• Background Sensitivity: immune complex glomerulonephritis develops by 1 year of age but is much milder than in MRL homozygotes

renal/urinary system

abnormal renal glomerulus morphology ( J:7454 )

• nephritic changes consist of focal increase in mesangial substance and mild mesangial proliferation

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

glomerulonephritis ( J:7454 )

• Background Sensitivity: immune complex glomerulonephritis develops by 1 year of age but is much milder than in MRL homozygotes

expanded mesangial matrix ( J:7454 )

• focal increase in mesangial substance

renal glomerular immunoglobulin deposits ( J:7454 )

cellular

increased mesangial cell number ( J:7454 )

• mild mesangial proliferation

increased apoptosis ( J:106288 )

• a trend toward increased apoptosis in airways is observed in anti-Il5 treated mutants after IP-IN OVA challenge

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

respiratory system

abnormal airway responsiveness ( J:106288 )

• mice intraperitoneally-injected (IP) with ovalbumin (OVA) and subsequently challenged intranasally (IN) with OVA develop airway hyperresponsiveness (AHR) at 48 hours and is significantly sustained at 96 hours but resolves at 6 days, whereas wild-type mice under same paradigm develop AHR at 48 hours but changes in airway resistance resolve by 96 hours

• treatment with anti-Il5 at 48 hours post-IP-IN challenge significantly attenuates AHR

Genotype
MGI:4944221

hm7

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: involves: 129P2/OlaHsd * MRL

mortality/aging

premature death ( J:26250 )

• about 10% of mice are moribund by 16 weeks of age

immune system

increased double-negative T cell number ( J:26250 )

• develop massive lymphadenopathy due to alpha beta DN T cell accumulation

increased gamma-delta T cell number ( J:26250 )

enlarged lymph nodes ( J:26250 )

• develop massive lymphadenopathy due to alpha beta DN T cell accumulation

kidney inflammation ( J:45448 )

• periglomerular infiltration

glomerulonephritis ( J:45448 )

• focal

homeostasis/metabolism

increased blood urea nitrogen level ( J:45448 )

• significantly elevated

increased urine protein level ( J:45448 )

• compared to age-matched B10.A mice

renal/urinary system

increased urine protein level ( J:45448 )

• compared to age-matched B10.A mice

kidney inflammation ( J:45448 )

• periglomerular infiltration

abnormal kidney morphology ( J:45448 )

abnormal renal glomerulus morphology ( J:45448 )

• glomerular hypercellularity

glomerulonephritis ( J:45448 )

• focal

hematopoietic system

increased double-negative T cell number ( J:26250 )

• develop massive lymphadenopathy due to alpha beta DN T cell accumulation

increased gamma-delta T cell number ( J:26250 )

Genotype
MGI:3694733

hm8

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: involves: C3H * MRL/Mp

immune system

increased spleen weight ( J:34296 )

• at 2 months of age and on

increased susceptibility to type III hypersensitivity reaction ( J:34296 )

• beginning at 4 month of age

autoimmune response ( J:1060 )

• systemic autoimmune disease occurred at 2-3 months of age

• characterized by elevated serum immune complexes, cryoglobulins, and antinuclear antibodies

increased susceptibility to systemic lupus erythematosus ( J:34296 )

• beginning at 4 month of age

increased anti-nuclear antigen antibody level ( J:34296 )

• beginning at 4 month of age

hearing/vestibular/ear

abnormal stria vascularis morphology ( J:1060 , J:34296 )

• degeneration of the stria vascularis was seen starting at 2 month and progressed throughout the lifespan (J:1060)

• early edema of the stria occurred in the apex and progressed basalward (J:1060)

• by 10 months of age, stria vascularis area was smaller (J:1060)

• no degeneration of hair cells was seen at any age (J:1060)

• edematous areas in the stria vascularis primarily in the basal turns due to enlarged extracellular spaces filled with fluid (J:34296)

• all sensorineural elements, inner and outer hair cells and spiral ganglion neurons appeared normal even in the 8-10 month-old mice with significant threshold shifts (J:34296)

abnormal stria vascularis vasculature morphology ( J:34296 )

• the stria capillaries often were larger than normal, and the endothelial cells were occasionally swollen or thickened due to hypertrophy and not hyperplasia

increased or absent threshold for auditory brainstem response ( J:1060 , J:34296 )

• the ABR thresholds of the 10-month-old mutant mice were significantly higher than those of wild-type C3H/HeJ controls (J:1060)

• the 2- and 4-month-old mutant mice had normal auditory thresholds similar to control (J:34296)

• after onset of systemic autoimmune disease at 3-4 months of age, threshold at 6 months were significantly elevated at 24 and 32 kHz (J:34296)

• threshold continued to rise and by 8 months 16 kHz was elevated as well (J:34296)

• threshold at the low frequencies (4 and 8 kHz) did not change with progression of systemic disease (J:34296)

hematopoietic system

increased spleen weight ( J:34296 )

• at 2 months of age and on

cardiovascular system

abnormal stria vascularis vasculature morphology ( J:34296 )

• the stria capillaries often were larger than normal, and the endothelial cells were occasionally swollen or thickened due to hypertrophy and not hyperplasia

growth/size/body

increased spleen weight ( J:34296 )

• at 2 months of age and on

Genotype
MGI:4361837

hm9

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: involves: C57BL/6 * MRL/Mp

immune system

enlarged spleen ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgA level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgG1 level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgG2a level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgG2b level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgG3 level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgM level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

lymph node hyperplasia ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased anti-double stranded DNA antibody level ( J:73396 )

• at day 275

increased anti-single stranded DNA antibody level ( J:73396 )

• at day 275

hematopoietic system

enlarged spleen ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgA level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgG1 level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgG2a level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgG2b level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgG3 level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

increased IgM level ( J:73396 )

• at day 175 and 275 compared with wild-type mice

growth/size/body

enlarged spleen ( J:73396 )

• at day 175 and 275 compared with wild-type mice

Genotype
MGI:3851804

hm10

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: involves: MRL/Mp

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:50903 )

• mice exhibit increased Pseudomonas aerugiosa exotoxin-induced mortality compared with similarly treated wild-type mice

immune system

decreased macrophage apoptosis ( J:154647 )

• macrophages exhibit 60% less cholesterol-induced apoptosis compared with similarly treated wild-type cells

increased susceptibility to bacterial infection ( J:50903 )

• mice exhibit increased Pseudomonas aerugiosa exotoxin-induced mortality compared with similarly treated wild-type mice

cellular

decreased macrophage apoptosis ( J:154647 )

• macrophages exhibit 60% less cholesterol-induced apoptosis compared with similarly treated wild-type cells

hematopoietic system

decreased macrophage apoptosis ( J:154647 )

• macrophages exhibit 60% less cholesterol-induced apoptosis compared with similarly treated wild-type cells

Genotype
MGI:3769145

hm11

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: MRL.Cg-Irf1^tm1Mak Fas^lpr

mortality/aging

premature death ( J:114771 )

• mice typically die by 26 weeks of age from renal failure; 50% of mice are dead by 22 weeks

renal/urinary system

increased urine protein level ( J:114771 )

• by 24 weeks of age, 75% of mice have urine protein levels >200 mg/dl

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show severe glomerulonephritis

renal glomerular immunoglobulin deposits ( J:114771 )

• mice show extensive glomerular deposition/staining of IgG and C3

kidney failure ( J:114771 )

• occurs around 26 weeks, leading to death

immune system

increased anti-double stranded DNA antibody level ( J:114771 )

• at 26 weeks of age, levels are significantly higher relative to Fas^lpr, Irf1-null mice

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show severe glomerulonephritis

homeostasis/metabolism

increased urine protein level ( J:114771 )

• by 24 weeks of age, 75% of mice have urine protein levels >200 mg/dl

integument

epidermal necrosis ( J:114771 )

• by 24 weeks, ear necrosis is observed in some mice

skin lesions ( J:114771 )

abnormal skin condition ( J:114771 )

• mice show characteristic signs of skin disease at 24 weeks of age

cellular

epidermal necrosis ( J:114771 )

• by 24 weeks, ear necrosis is observed in some mice

Genotype
MGI:3800241

hm12

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: MRL.Cg-Tnfrsf9^tm1Byk Fas^lpr

mortality/aging

premature death ( J:127197 )

• by 5 months, 40% mortality is observed

integument

skin lesions ( J:127197 )

• by 5 months, skin lesions develop around tip of nose and around the ears

Genotype
MGI:3761609

hm13

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: MRL-Fas^lpr

immune system

increased spleen weight ( J:126261 )

• mean weight is 0.9 grams

increased immunoglobulin level ( J:6257 )

• splenic cells in culture show four- to sixfold higher frequencies of spontaneous immunoglobulin release than controls

increased IgG level ( J:126261 )

• twice wild-type levels

increased IgM level ( J:126261 )

• about 1.7 fold higher than wild-type levels

abnormal T-helper 2 physiology ( J:6257 )

• enhanced T-helper cell activity is seen in vitro; removal of T cells from splenic cultures resulted in a significant reduction of the frequency of spontaneous immunoglobulin release in both autoimmune and normal spleen cell populations

• T cell-enriched populations from older animals provided twice the help offered by T cells of young syngeneic animals or T cells from young and older normal mice of the same H-2 haplotype

enlarged lymph nodes ( J:126261 )

• mean weight of axillary lymph nodes is 1.3 grams

increased anti-nuclear antigen antibody level ( J:126261 )

• levels are elevated compared to wild-type mice

increased anti-double stranded DNA antibody level ( J:126261 )

• 30 fold higher than in mice without autoimmune disease

glomerulonephritis ( J:126261 )

• lymphocyte infiltration, lobulation, and hyaline deposition noted in kidney

homeostasis/metabolism

increased blood urea nitrogen level ( J:126261 )

• mean levels are 52.4 mg/dl

hematopoietic system

increased spleen weight ( J:126261 )

• mean weight is 0.9 grams

increased immunoglobulin level ( J:6257 )

• splenic cells in culture show four- to sixfold higher frequencies of spontaneous immunoglobulin release than controls

increased IgG level ( J:126261 )

• twice wild-type levels

increased IgM level ( J:126261 )

• about 1.7 fold higher than wild-type levels

abnormal T-helper 2 physiology ( J:6257 )

• enhanced T-helper cell activity is seen in vitro; removal of T cells from splenic cultures resulted in a significant reduction of the frequency of spontaneous immunoglobulin release in both autoimmune and normal spleen cell populations

• T cell-enriched populations from older animals provided twice the help offered by T cells of young syngeneic animals or T cells from young and older normal mice of the same H-2 haplotype

cardiovascular system

vascular inflammation ( J:126261 )

• observed in kidneys with destruction of external elastic lamina common

renal/urinary system

glomerulonephritis ( J:126261 )

• lymphocyte infiltration, lobulation, and hyaline deposition noted in kidney

growth/size/body

increased spleen weight ( J:126261 )

• mean weight is 0.9 grams

Genotype
MGI:3613077

hm14

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: MRL/Mp-Agtpbp1^atms Fas^lpr

growth/size/body

increased body weight ( J:103944 )

• body weight is increased by 3 weeks of age in homozygotes that may or may not be heterozygous for atms

enlarged spleen ( J:103944 )

hematopoietic system

enlarged thymus ( J:103944 )

enlarged spleen ( J:103944 )

immune system

enlarged thymus ( J:103944 )

enlarged spleen ( J:103944 )

enlarged lymph nodes ( J:103944 )

• develop lymphadenopathy

neoplasm

increased tumor incidence ( J:103944 )

• develop subcutaneous tumors

integument

ruffled hair ( J:103944 )

• ruffled hair due to superficial prominent lymphadenopathy

endocrine/exocrine glands

enlarged thymus ( J:103944 )

Genotype
MGI:2450135

hm15

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: MRL/Mp-Fas^lpr

mortality/aging

premature death ( J:13757 , J:27634 , J:28885 )

• mean age of death in females was 17 weeks of age (J:13757)

• mean age of death in males was 22 weeks of age (J:13757)

• 50% mortality is observed at 5 or 5.5 months for females and males with 90% mortality at 7.3 or 8.6 months in females and males (J:27634)

• life span of females is 120+/-4 days (J:28885)

• life span of males is 154+/-32 days (J:28885)

immune system

abnormal B cell morphology ( J:108760 )

• frequency of C3d receptor bearing cells declines with age

abnormal B cell receptor editing ( J:131138 )

• Anti-dsDNA B cells escape receptor editing

abnormal T cell morphology ( J:8267 , J:108760 )

• lymph node cells (T cell origin) are abnormal; cells are Ly-2^-/L3T4^-/surface Ig^- (J:8267)

• increase in T-cell frequencies and absolute numbers with advanced disease; however, the number of Ly123+ and Ly23+ T cells is markedly decreased in older mice compared to young mice (J:108760)

abnormal immune system organ morphology ( J:28885 )

abnormal thymus medulla morphology ( J:28885 )

• increase in thymus weight restricted to the medulla

enlarged thymus ( J:13757 )

• slighlty enlarged

increased thymus weight ( J:28885 )

• doubling of thymus weight

thymus atrophy ( J:27634 )

• thymic atrophy is observed; severity is most severe in the cortex but usually involves the medulla in most animals

• initial lesion is loss of cortical thymocytes, with later degeneration (cystic) of thymocytes of medulla

• in 5-10% of animals, there is medullary or stromal hyperplasia that maintains or increases the size of the thymus

thymus cortex atrophy ( J:13757 , J:28885 )

• atrophic cortex (J:13757)

enlarged spleen ( J:28885 )

• spleen is 7-fold larger than controls

abnormal marginal zone B cell morphology ( J:131138 )

• mice have a larger marginal zone B cell population (10.8% of splenic lymphocytes) compared to BALB/c controls (1.9%)

enlarged Peyer's patches ( J:28885 )

• slight enlargement

abnormal lymph node morphology ( J:27634 )

• in mice with lymph node hyperplasia, larger nodes show extensive hemorrhage and cystic necrosis, which results in clinically observed terminal reduction in size

lymph node necrosis ( J:27634 )

• in mice with lymph node hyperplasia, larger nodes show extensive cystic necrosis

abnormal lymph node cell ratio ( J:6257 )

• mice show 4- to 6-fold higher frequencies of immunoglobulin-secreting cells (IgSC) compared to normal controls

enlarged lymph nodes ( J:13757 , J:27634 , J:28885 , J:108760 )

• enlargement started at 8 weeks of age and progressed until lymph node weights were 100 times control lymph node weight by 16 weeks of age (J:13757)

• node architecture was blurred, with proliferation of lymphocytes with some admixture of plasma cells and histiocytes (J:13757)

• no evidence of malignancy was present, despite enlargement (J:13757)

• all mice begin to develop generalized lymph lymphadenopathy when >3 months of age; in about 33%. lymph nodes shrink markedly 7-10 days before death (J:27634)

lymph node hyperplasia ( J:27634 )

• lymph nodes are up to 100 times normal size

abnormal immune system physiology ( J:28885 )

lymph node hemorrhage ( J:27634 )

• in mice with lymph node hyperplasia, larger nodes show extensive hemorrhage

blood vessel inflammation ( J:28885 )

• arteritis is observed in a number of organs, and is associated with hemorrhage and infarcts in the lymph nodes

salivary gland inflammation ( J:18512 )

• lymphocytic infiltration and lymphocytic foci are observed in mice 3.4-3.7 months of age

• treatment with danazol or Org 4094 sifnificantly lowers number of foci and percentage of lymphocyte infiltration, as well as other immune parameters compared to untreated controls

submandibular gland inflammation ( J:21965 )

• autoimmune sialodenitis with parenchymal destruction is observed in 4-6 month old mice in submandibular salivary glands of female mice

• most infiltrating cells are CD4⁺ and Vbeta8⁺ with a minority being CD4⁺ and Vbeta6⁺

thyroid gland inflammation ( J:28171 )

• animals display thyroid gland infiltration (autoimmune thyroiditis)

lacrimal gland inflammation ( J:18512 )

• adult lacrimal glands show infiltration by lymphocytes

• treatment with steroids alleviates lymphocyte infiltration

increased immunoglobulin level ( J:6257 , J:13757 , J:28885 )

• mice show 4- to 6-fold higher frequencies of immunoglobulin-secreting cells in spleens compared to normal controls (J:6257)

• hypergammaglobulinemia (J:13757)

increased IgA level ( J:28885 )

• 2-fold increase

increased IgG level ( J:27634 )

• at 2-3 months, concentration are up to 5 times control and 8 times control at 5 months

increased IgG1 level ( J:13757 , J:28885 )

• 10-fold increase (J:28885)

increased IgG2a level ( J:13757 , J:28885 )

• 10-fold increase (J:28885)

increased IgG2b level ( J:28885 )

• 2-fold increase

increased IgM level ( J:28885 )

• 2-fold increase

abnormal T cell physiology ( J:8267 )

• cells do not generate CTL in response to stimulation with alloantigens

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

abnormal T-helper 2 physiology ( J:6257 )

• activity of helper T cells is enhanced in older mice relative to younger animals or normal controls

abnormal cytotoxic T cell physiology ( J:7488 )

• 4-6 month old mice exhibit significantly depressed cytotoxic T cell response to alloantigens

abnormal interleukin level ( J:8267 )

• stimulation with concanavalin A does not induce cells to produce Il2

abnormal type III hypersensitivity reaction ( J:28885 )

• perivascular infiltration of lymphocytes, plasma cells, and histiocytes in lung, kidney, salivary gland and liver

• perivascular and peribronchial lymphoproliferation observed in lung reslting in patches of atelectasis and exudate containing patches

decreased interleukin-2 secretion ( J:6638 , J:7488 )

• early in life, mice show reduced Il2 production, that worsens with age, such that almost no Il2 activity is detected in culture supernatants from 2 month old animals; spleen cells show no stimulated Il2 production upon stimulation with concanavalin A (J:6638)

• mice have severe deficiency in Il-2 production (J:7488)

increased susceptibility to autoimmune disorder ( J:108760 )

increased autoantibody level ( J:28885 )

• thymocytoxic autoantibodies are detected with aging

increased anti-erythrocyte antigen antibody level ( J:27634 )

• levels reach 4 and 11% in males and females

increased anti-nuclear antigen antibody level ( J:27634 , J:28885 )

• anti-Sm antibodies are detected in males and females but not in controls (J:27634)

• anti-nuclear antigen antibody (ANA) activity in renal eluate Ig is much higher than activity in serum Ig for anti-ssDNA and anti-dsDNA (J:27634)

• antinuclear antibody titers are detectable at 8 weeks of age and increased rapidly (J:28885)

increased anti-double stranded DNA antibody level ( J:6257 , J:27634 , J:131138 )

• 4-month old mice show around 4-fold higher number of spleen cells secreting autoantibodies to dsDNA compared to 8-month old wild-type controls. (J:6257)

• high levels detected at 4-5 months (J:27634)

• significant levels of IgM and IgG antibodies that bind dsDNA antibodies are detected in mice 6-8 weeks of age (J:131138)

• levels of these auto antibodies rise with age (J:131138)

increased anti-single stranded DNA antibody level ( J:27634 )

• detected at significant levels at 2 months, with very high levels detected at 4-5 months

glomerulonephritis ( J:13757 , J:27634 , J:28885 )

• immune complex glomerulonephritis (J:13757)

• mice show a largely subacute proliferative form of disease; lesions involve proliferation of endothelial and mesangial cells (J:27634)

• glomerular lesions involve proliferation of both endothelial and mesangial cells and basement membrane thickening (J:28885)

• granular deposits of immunoglobulins present in the capillary walls (J:28885)

• capsular cell proliferation, tubular damage, and casts were seen in severe lesions (J:28885)

renal/urinary system

abnormal glomerular capillary morphology ( J:28885 )

• granular deposits of immunoglobulins present in the capillary walls

abnormal glomerular capillary endothelium morphology ( J:28885 )

• proliferation of endothelial cells

increased mesangial cell number ( J:28885 )

• proliferation of mesangial cells

increased kidney cell proliferation ( J:27634 )

• glomerular lesions involve proliferation of endothelial and mesangial cells

increased urine protein level ( J:28885 )

• incomplete penetrance, 50% of females tested have a 9-fold increase over controls

glomerulonephritis ( J:13757 , J:27634 , J:28885 )

• immune complex glomerulonephritis (J:13757)

• mice show a largely subacute proliferative form of disease; lesions involve proliferation of endothelial and mesangial cells (J:27634)

• glomerular lesions involve proliferation of both endothelial and mesangial cells and basement membrane thickening (J:28885)

• granular deposits of immunoglobulins present in the capillary walls (J:28885)

• capsular cell proliferation, tubular damage, and casts were seen in severe lesions (J:28885)

increased renal glomerulus basement membrane thickness ( J:28885 )

• glomerular basement membrane thickening

glomerular crescent ( J:28885 )

• capsular cell proliferation is seen in severe glomerular lesions

renal glomerular protein deposits ( J:27634 )

• between 2 and 5 months, granular IgG and C3 deposits increase in capillary wall and mesangium

renal glomerular immunoglobulin deposits ( J:13757 , J:27634 )

renal cast ( J:28885 )

• casts were seen in severe glomerular lesions

homeostasis/metabolism

abnormal circulating protein level ( J:27634 )

• mice have high concentrations of circulating immune complex at 2-3 and 4-5 months

• high levels of cyroglobulins are found in mice at 5 months

increased circulating serum albumin level ( J:28885 )

increased circulating total protein level ( J:28885 )

• total serum protein levels are slightly increased

• 2-fold increase in beta- and 5-fold increase in gamma-globulins

joint swelling ( J:27634 )

• 20-25% of old, diseased mice show joint swelling of the hind feet and lower legs; involving destruction of articular cartilage, proliferation of synovium, pannus formations, and sometimes joint effusions

abnormal interleukin level ( J:8267 )

• stimulation with concanavalin A does not induce cells to produce Il2

increased urine protein level ( J:28885 )

• incomplete penetrance, 50% of females tested have a 9-fold increase over controls

hematopoietic system

abnormal thymus medulla morphology ( J:28885 )

• increase in thymus weight restricted to the medulla

enlarged thymus ( J:13757 )

• slighlty enlarged

increased thymus weight ( J:28885 )

• doubling of thymus weight

thymus atrophy ( J:27634 )

• thymic atrophy is observed; severity is most severe in the cortex but usually involves the medulla in most animals

• initial lesion is loss of cortical thymocytes, with later degeneration (cystic) of thymocytes of medulla

• in 5-10% of animals, there is medullary or stromal hyperplasia that maintains or increases the size of the thymus

thymus cortex atrophy ( J:13757 , J:28885 )

• atrophic cortex (J:13757)

enlarged spleen ( J:28885 )

• spleen is 7-fold larger than controls

abnormal B cell morphology ( J:108760 )

• frequency of C3d receptor bearing cells declines with age

abnormal B cell receptor editing ( J:131138 )

• Anti-dsDNA B cells escape receptor editing

abnormal marginal zone B cell morphology ( J:131138 )

• mice have a larger marginal zone B cell population (10.8% of splenic lymphocytes) compared to BALB/c controls (1.9%)

abnormal T cell morphology ( J:8267 , J:108760 )

• lymph node cells (T cell origin) are abnormal; cells are Ly-2^-/L3T4^-/surface Ig^- (J:8267)

• increase in T-cell frequencies and absolute numbers with advanced disease; however, the number of Ly123+ and Ly23+ T cells is markedly decreased in older mice compared to young mice (J:108760)

increased immunoglobulin level ( J:6257 , J:13757 , J:28885 )

• mice show 4- to 6-fold higher frequencies of immunoglobulin-secreting cells in spleens compared to normal controls (J:6257)

• hypergammaglobulinemia (J:13757)

increased IgA level ( J:28885 )

• 2-fold increase

increased IgG level ( J:27634 )

• at 2-3 months, concentration are up to 5 times control and 8 times control at 5 months

increased IgG1 level ( J:13757 , J:28885 )

• 10-fold increase (J:28885)

increased IgG2a level ( J:13757 , J:28885 )

• 10-fold increase (J:28885)

increased IgG2b level ( J:28885 )

• 2-fold increase

increased IgM level ( J:28885 )

• 2-fold increase

abnormal T cell physiology ( J:8267 )

• cells do not generate CTL in response to stimulation with alloantigens

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

abnormal T-helper 2 physiology ( J:6257 )

• activity of helper T cells is enhanced in older mice relative to younger animals or normal controls

abnormal cytotoxic T cell physiology ( J:7488 )

• 4-6 month old mice exhibit significantly depressed cytotoxic T cell response to alloantigens

cardiovascular system

abnormal coronary artery morphology ( J:27634 )

abnormal glomerular capillary morphology ( J:28885 )

• granular deposits of immunoglobulins present in the capillary walls

abnormal glomerular capillary endothelium morphology ( J:28885 )

• proliferation of endothelial cells

abnormal cardiovascular system physiology ( J:27634 )

• 15-30% of mice suffer old and/or acute myocardial infarction involving either ventricle and judged severe enough to contribute to death

lymph node hemorrhage ( J:27634 )

• in mice with lymph node hyperplasia, larger nodes show extensive hemorrhage

blood vessel inflammation ( J:28885 )

• arteritis is observed in a number of organs, and is associated with hemorrhage and infarcts in the lymph nodes

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:18512 )

N • lymphatic tissues that undergo age-related increase in weight due to lymphocytic accumulation are decreased in weight with cyclophosphamide treatment compared to placebo treated controls

salivary gland inflammation ( J:18512 )

• lymphocytic infiltration and lymphocytic foci are observed in mice 3.4-3.7 months of age

• treatment with danazol or Org 4094 sifnificantly lowers number of foci and percentage of lymphocyte infiltration, as well as other immune parameters compared to untreated controls

submandibular gland inflammation ( J:21965 )

• autoimmune sialodenitis with parenchymal destruction is observed in 4-6 month old mice in submandibular salivary glands of female mice

• most infiltrating cells are CD4⁺ and Vbeta8⁺ with a minority being CD4⁺ and Vbeta6⁺

abnormal gland morphology ( J:18512 )

• dexamethasone treatment increases weight of lacrimal tissue compared to untreated mice; treatment results in a reduction in tear volume

abnormal submandibular gland morphology ( J:18512 )

• treatment with androgens increases gland weight in mutants

• this treatment significantly decreases lymphocytic infiltration into submandibular glands

abnormal thymus medulla morphology ( J:28885 )

• increase in thymus weight restricted to the medulla

enlarged thymus ( J:13757 )

• slighlty enlarged

increased thymus weight ( J:28885 )

• doubling of thymus weight

thymus atrophy ( J:27634 )

• thymic atrophy is observed; severity is most severe in the cortex but usually involves the medulla in most animals

• initial lesion is loss of cortical thymocytes, with later degeneration (cystic) of thymocytes of medulla

• in 5-10% of animals, there is medullary or stromal hyperplasia that maintains or increases the size of the thymus

thymus cortex atrophy ( J:13757 , J:28885 )

• atrophic cortex (J:13757)

abnormal thyroid gland morphology ( J:28171 )

• inflamed tissue has massive infiltration organized into lymphoid follicle centers and extensive interstitially distributed lymphocytes

• fibrosis is minimal, with only 1% of tissue displaying fibroblast growth; when detected, fibrosis is adjacent to atrophic follicles

• functional communication between cells in thyroid cell cultures is dramatically reduced

abnormal thyroid follicle morphology ( J:28171 )

• marked decrease in follicle size is noted proceeding from center of lobe toward periphery

thyroid gland inflammation ( J:28171 )

• animals display thyroid gland infiltration (autoimmune thyroiditis)

lacrimal gland inflammation ( J:18512 )

• adult lacrimal glands show infiltration by lymphocytes

• treatment with steroids alleviates lymphocyte infiltration

skeleton

joint swelling ( J:27634 )

• 20-25% of old, diseased mice show joint swelling of the hind feet and lower legs; involving destruction of articular cartilage, proliferation of synovium, pannus formations, and sometimes joint effusions

digestive/alimentary system

abnormal submandibular gland morphology ( J:18512 )

• treatment with androgens increases gland weight in mutants

• this treatment significantly decreases lymphocytic infiltration into submandibular glands

salivary gland inflammation ( J:18512 )

• lymphocytic infiltration and lymphocytic foci are observed in mice 3.4-3.7 months of age

• treatment with danazol or Org 4094 sifnificantly lowers number of foci and percentage of lymphocyte infiltration, as well as other immune parameters compared to untreated controls

submandibular gland inflammation ( J:21965 )

• autoimmune sialodenitis with parenchymal destruction is observed in 4-6 month old mice in submandibular salivary glands of female mice

• most infiltrating cells are CD4⁺ and Vbeta8⁺ with a minority being CD4⁺ and Vbeta6⁺

vision/eye

lacrimal gland inflammation ( J:18512 )

• adult lacrimal glands show infiltration by lymphocytes

• treatment with steroids alleviates lymphocyte infiltration

integument

skin lesions ( J:28885 )

• lesions accompanied by hair loss and scab formation were common

• erythemateous lesions of the ear often become necrotic

cellular

increased mesangial cell number ( J:28885 )

• proliferation of mesangial cells

lymph node necrosis ( J:27634 )

• in mice with lymph node hyperplasia, larger nodes show extensive cystic necrosis

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

increased kidney cell proliferation ( J:27634 )

• glomerular lesions involve proliferation of endothelial and mesangial cells

growth/size/body

enlarged spleen ( J:28885 )

• spleen is 7-fold larger than controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autoimmune lymphoproliferative syndrome		DOID:6688	OMIM:601859	J:28885
Sjogren's syndrome		DOID:12894	OMIM:270150	J:1028 , J:18512 , J:21965
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:27634 , J:28885 , J:108760 , J:131138

Genotype
MGI:3799686

hm16

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: MRL/MpJ-Fas^lpr

mortality/aging

premature death ( J:125114 , J:137066 )

• animals start to die at 4.5 months, with >50% mortality observed at 7 months (J:125114)

• 50% mortality by 20 weeks; <40% survival beyond 40 weeks (J:137066)

hematopoietic system

abnormal leukocyte adhesion ( J:126009 )

• significantly enhanced at 12 and 16 weeks

impaired leukocyte tethering or rolling ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

enlarged spleen ( J:137066 )

• severe

abnormal leukocyte morphology ( J:126009 )

• 46% of venules display leukocytes adjacent to endothelium, compared to only 145 in controls; in mutants and controls, 60-70% of these cells are mononuclear

increased double-negative T cell number ( J:137066 )

• significantly increased relative to controls

decreased B cell number ( J:137066 )

decreased CD4-positive, alpha-beta T cell number ( J:137066 )

• reduced compared to wild-type MRL animals

decreased CD8-positive, alpha-beta T cell number ( J:137066 )

• reduced compared to wild-type MRL animals

decreased activated T cell number ( J:137066 )

increased immunoglobulin level ( J:125114 )

• mice develop hypergammaglobulinemia

immune system

blood vessel inflammation ( J:137066 )

• mice develop systemic necrotizing arteritis of small- and medium-sized arteries; frequently observed in kidneys

abnormal leukocyte adhesion ( J:126009 )

• significantly enhanced at 12 and 16 weeks

impaired leukocyte tethering or rolling ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

enlarged spleen ( J:137066 )

• severe

abnormal leukocyte morphology ( J:126009 )

• 46% of venules display leukocytes adjacent to endothelium, compared to only 145 in controls; in mutants and controls, 60-70% of these cells are mononuclear

increased double-negative T cell number ( J:137066 )

• significantly increased relative to controls

decreased B cell number ( J:137066 )

decreased CD4-positive, alpha-beta T cell number ( J:137066 )

• reduced compared to wild-type MRL animals

decreased CD8-positive, alpha-beta T cell number ( J:137066 )

• reduced compared to wild-type MRL animals

decreased activated T cell number ( J:137066 )

increased immunoglobulin level ( J:125114 )

• mice develop hypergammaglobulinemia

enlarged lymph nodes ( J:137066 )

• severe

autoimmune response ( J:125114 )

• mice develop anti-nuclear antibodies (ie. anti-dsDNA, anti-ssDNA, etc)

increased autoantibody level ( J:137066 )

• IgG3 anti-IgG2a rheumatoid factor (RF) levels are much higher than wild-type controls

increased anti-nuclear antigen antibody level ( J:137066 )

• levels of anti-dsDNA and anti-chromatin autoantibodies are elevated compared to wild-type

glomerulonephritis ( J:125114 , J:132514 , J:137066 )

• mice show deposition of IgG or C3 in kidneys and inflammation (J:125114)

cardiovascular system

blood vessel inflammation ( J:137066 )

• mice develop systemic necrotizing arteritis of small- and medium-sized arteries; frequently observed in kidneys

renal/urinary system

glomerulonephritis ( J:125114 , J:132514 , J:137066 )

• mice show deposition of IgG or C3 in kidneys and inflammation (J:125114)

renal glomerular immunoglobulin deposits ( J:125114 )

cellular

abnormal leukocyte adhesion ( J:126009 )

• significantly enhanced at 12 and 16 weeks

impaired leukocyte tethering or rolling ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

growth/size/body

enlarged spleen ( J:137066 )

• severe

Genotype
MGI:3639605

hm17

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: MRL/MpJ-Fas^lpr/J

mortality/aging

premature death ( J:7454 )

• 50% mortality is observed at 5 months with 90% mortality at 7.5 months, significantly reduced from wild-type

cellular

increased mesangial cell number ( J:127199 )

• mild increase in mesangial cells is seen at 20 weeks of age

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

immune system

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

lymph node necrosis ( J:7454 )

• larger lymph nodes often show extensive necrosis

salivary gland inflammation ( J:92084 )

decreased immature B cell number ( J:122315 )

• CD19+IgM+ immature B cells are reduced in the spleen

decreased transitional stage B cell number ( J:122315 )

• numbers of the T1 subset of B cells is reduced

increased neutrophil cell number ( J:127199 )

• mild to moderated neutrophil accumulation is observed at 20 weeks

decreased mature B cell number ( J:122315 )

• CD19+ IgD^high IgM^low B cells are severely reduced in the spleen

decreased marginal zone B cell number ( J:122315 )

• numbers of marginal zone (MZ) B cells is reduced

increased plasma cell number ( J:122315 )

• increased B220+IgM+ cells are observed in bone marrow; number of IgG-secreting cells are significantly increased compared to Fas^lpr homozygotes

decreased spleen germinal center number ( J:122315 )

• staining intensity and number of germinal centers (GCs) is reduced 10 days post-challenge with NP-KLH antigen, compared to controls

abnormal immunoglobulin level ( J:122315 )

• in vitro, splenic B cells produce significantly higher amounts of IgG1 in response to LPS and anti-CD40 plus Il4 stimulation, and higher amounts of IgG2a upon LPS stimulation

decreased IgG level ( J:122315 )

• production of anti-NP IgG is impaired in spleen cells

increased immunoglobulin level ( J:7454 , J:122315 )

• IgG and IgM levels are increased in serum at 6 months (J:7454)

• mice display hypergammaglobulinemia; serum levels are comparable to Fas homozygotes (J:122315)

increased IgG level ( J:92084 )

• mice exhibit increased serum IgG levels and IgG deposits in the kidney unlike wild-type mice

enlarged lymph nodes ( J:7454 , J:92084 )

• nodes are 62 times normal size (J:7454)

increased susceptibility to systemic lupus erythematosus ( J:92084 )

• mice exhibit increased serum levels of kappa-chain rheumatoid factor and DNA auto-antibodies, lymphadenopathy, glomerulonephritis, renal immunoglobulin deposits, proteinuria, and end organ disease compared to in wild-type mice

increased autoantibody level ( J:14151 , J:92084 )

• at 16 weeks, levels of anti-cardiolipin antibodies are significantly higher than in wild-type controls; levels are significantly higher at 8 weeks (J:14151)

• mice exhibit increased serum levels of kappa-chain rheumatoid factor compared to in wild-type mice (J:92084)

increased anti-nuclear antigen antibody level ( J:7454 , J:14151 , J:92084 , J:111811 )

• mice have significantly increased levels of anti-ssDNA antibodies (J:7454)

• at 16 weeks, anti-DNA titers are significantly higher than in wild-type controls (J:14151)

• DNA auto-antibodies are increased compared to in wild-type mice at 12 weeks (J:92084)

• by 5-6 months of age, Fas-deficient mice have antinuclear antibody (ANA) levels comparable to >50% of C4b-deficient females (on Igh^b haplotype homozygous background) (J:111811)

increased anti-double stranded DNA antibody level ( J:7454 , J:92084 , J:122315 )

• antibodies are increased relative to controls and other mutant strains with Fas^lpr mutations (J:7454)

• mice produce high titers of IgG1 and IgG2a anti-dsDNA antibodies, comparable to Fas homozygotes (J:122315)

CNS inflammation ( J:14151 )

• at 20 weeks, all mice show mononuclear infiltrates in the choroid plexus; at 10 weeks, all mice display monuclear infiltrates

conjunctivitis ( J:123192 )

glomerulonephritis ( J:7454 , J:92084 , J:122315 , J:127199 )

• Background Sensitivity: severe immune complex glomerulonephritis develops by 6 months (J:7454)

• mice show deposition of IgG or C3 in kidneys and inflammation, similar to Fas homozygotes (J:122315)

• kidney lesions have lower scores than those in double mutants at 20 weeks (J:127199)

muscle

abnormal myocardium layer morphology ( J:14151 )

• myocardium neighboring the heart valves shows mononuclear infiltration of the vessels, but valves are normal

hematopoietic system

decreased immature B cell number ( J:122315 )

• CD19+IgM+ immature B cells are reduced in the spleen

decreased transitional stage B cell number ( J:122315 )

• numbers of the T1 subset of B cells is reduced

increased neutrophil cell number ( J:127199 )

• mild to moderated neutrophil accumulation is observed at 20 weeks

decreased mature B cell number ( J:122315 )

• CD19+ IgD^high IgM^low B cells are severely reduced in the spleen

decreased marginal zone B cell number ( J:122315 )

• numbers of marginal zone (MZ) B cells is reduced

increased plasma cell number ( J:122315 )

• increased B220+IgM+ cells are observed in bone marrow; number of IgG-secreting cells are significantly increased compared to Fas^lpr homozygotes

decreased spleen germinal center number ( J:122315 )

• staining intensity and number of germinal centers (GCs) is reduced 10 days post-challenge with NP-KLH antigen, compared to controls

abnormal immunoglobulin level ( J:122315 )

• in vitro, splenic B cells produce significantly higher amounts of IgG1 in response to LPS and anti-CD40 plus Il4 stimulation, and higher amounts of IgG2a upon LPS stimulation

decreased IgG level ( J:122315 )

• production of anti-NP IgG is impaired in spleen cells

increased immunoglobulin level ( J:7454 , J:122315 )

• IgG and IgM levels are increased in serum at 6 months (J:7454)

• mice display hypergammaglobulinemia; serum levels are comparable to Fas homozygotes (J:122315)

increased IgG level ( J:92084 )

• mice exhibit increased serum IgG levels and IgG deposits in the kidney unlike wild-type mice

renal/urinary system

increased urine protein level ( J:92084 , J:122315 )

albuminuria ( J:122315 )

• mice have excessive urinary albumin compared to wild-type (>10-fold) at 3-4 months

podocyte foot process effacement ( J:127199 )

• foot processes are only focally effaced

dilated renal glomerular capsule ( J:122315 )

• dilated capsules are observed in mice at 3-4 months

abnormal renal glomerulus morphology ( J:7454 , J:127199 )

• abnormalities due to severe glomerulonephritis (J:7454)

• at 20 weeks, lesions show some neutrophil infiltration and hypercellularity (J:127199)

• tuft necrosis, capsular proliferation and fibrosis are less common and less severe than observed in double mutants (J:127199)

increased mesangial cell number ( J:127199 )

• mild increase in mesangial cells is seen at 20 weeks of age

expanded mesangial matrix ( J:127199 )

• mild increase in mesangial matrix is seen at 20 weeks of age

cortical renal glomerulopathies ( J:122315 )

• glomerulonephritic changes such as hypercellularity, lobularity, dilated capsules and crescent formation or enlarged glomeruli are observed in mice at 3-4 months

glomerulonephritis ( J:7454 , J:92084 , J:122315 , J:127199 )

• Background Sensitivity: severe immune complex glomerulonephritis develops by 6 months (J:7454)

• mice show deposition of IgG or C3 in kidneys and inflammation, similar to Fas homozygotes (J:122315)

• kidney lesions have lower scores than those in double mutants at 20 weeks (J:127199)

glomerular crescent ( J:122315 )

• crescent formation is observed in mice at 3-4 months

renal glomerulus hypertrophy ( J:122315 )

• enlarged glomeruli are observed in mice at 3-4 months

abnormal kidney physiology ( J:127199 )

• progressive decline in renal function is observed, during progression to end-stage renal disease

behavior/neurological

abnormal spatial learning ( J:14151 )

• mice show increased latency to locate hidden platform in water maze testing on days 2-5 of testing at 8 weeks of age; at 16 weeks in spatial bias testing, mutants spend less time and travel reduced distances in quadrant of platform's previous location compared to controls

impaired coordination ( J:14151 )

• equilibrium is significantly impaired in mice at 18-20 weeks, as measured by performance in rotarod tests

vision/eye

vision/eye phenotype ( J:123192 )

N

conjunctivitis ( J:123192 )

abnormal conjunctival epithelium morphology ( J:123192 )

cardiovascular system

abnormal myocardium layer morphology ( J:14151 )

• myocardium neighboring the heart valves shows mononuclear infiltration of the vessels, but valves are normal

lymph node hemorrhage ( J:7454 )

• larger lymph nodes often show extensive hemorrhage

vascular inflammation ( J:127199 )

hearing/vestibular/ear

abnormal stria vascularis morphology ( J:3638 )

• widened intercellular space in the stria vascularis

• slight degenerative changes in the stria vascularis of both the apical and basal turns

• the basement membrane of the capillaries in the stria vascularis was thickened

• the basal infolding of strial marginal cells

abnormal strial intermediate cell morphology ( J:3638 )

• thinned intermediate cell layer

increased or absent threshold for auditory brainstem response ( J:3638 )

• the ABR threshold f the 20-week-old mutant mice were significantly higher than those of the 4-week-old mutant mice and the 20-week-old wild-type BALB/c mice

nervous system

CNS inflammation ( J:14151 )

• at 20 weeks, all mice show mononuclear infiltrates in the choroid plexus; at 10 weeks, all mice display monuclear infiltrates

homeostasis/metabolism

increased urine protein level ( J:92084 , J:122315 )

albuminuria ( J:122315 )

• mice have excessive urinary albumin compared to wild-type (>10-fold) at 3-4 months

abnormal enzyme/coenzyme activity ( J:109815 )

• Background Sensitivity: 7-8 week old mice show 2-3 fold induction of Dnase1l3 in macrophages and 4-5 fold induction in splenocytes over C57BL/6; levels in other strains like BXSB/MpJ and (NZB x NZW)F1 are similarly elevated compared to B6

• Background Sensitivity: mice show a dramatic defect (~8-fold decrease) in macrophage-secreted Dnase1l3 barrier to liposomal (BT) activity compared to B6; (NZB x NZW)F1 mice show a similar defect in BT activity

pigmentation

abnormal strial intermediate cell morphology ( J:3638 )

• thinned intermediate cell layer

digestive/alimentary system

salivary gland inflammation ( J:92084 )

endocrine/exocrine glands

salivary gland inflammation ( J:92084 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:123192

Genotype
MGI:3622771

hm18

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: NOD.MRL(B6)-Fas^lpr

immune system

decreased susceptibility to autoimmune diabetes ( J:64051 )

• during the 24 week period, no animals show diabetes or insulitis (mice are considered diabetic after a blood glucose measure of >300 mg/dl)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	type 1 diabetes mellitus	DOID:9744	OMIM:222100	J:64051

Genotype
MGI:3663022

hm19

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: NOD.MRL-Fas^lpr

immune system

decreased susceptibility to autoimmune diabetes ( J:78679 )

• when mice are injected with islet specific CD8+ T cell clones, Fas^lpr mice are resistant to diabetogenic effect of injected T cells; 0/5 of Fas mutants are diabetic within 20 day observation period, while control NOD littermates become diabetic within 6 days

Genotype
MGI:3690618

ht20

• Allelic Composition: Fas^lpr/Fas^tm1.1Cgn
• Genetic Background: involves: C57BL/6 * MRL

hematopoietic system

enlarged spleen ( J:114948 )

immune system

abnormal immune system morphology ( J:114948 )

• develop the typical Fas^lpr homozygous phenotype

enlarged spleen ( J:114948 )

enlarged lymph nodes ( J:114948 )

growth/size/body

enlarged spleen ( J:114948 )

Genotype
MGI:6694199

cn21

• Allelic Composition: Fas^lpr/Fas^lpr; Hspa13^tm1.1Smoc/Hspa13^tm1.1Smoc; Cd19^tm1(cre)Cgn/Cd19⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S * C57BL/6 * MRL/Mp

immune system

decreased susceptibility to systemic lupus erythematosus ( J:303927 )

• mice exhibit reduced increase in autoantibody levels and proteinuria levels compared with control mice

decreased autoantibody level ( J:303927 )

• compared with Fas^lpr homozygotes

renal/urinary system

increased urine protein level ( J:303927 )

• not as severe as in Fas^lpr homozygotes

homeostasis/metabolism

increased urine protein level ( J:303927 )

• not as severe as in Fas^lpr homozygotes

Genotype
MGI:3690553

cn22

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Fas^lpr/Fas^tm1Cgn; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2 * MRL

immune system

enlarged spleen ( J:114948 )

• similar to mice with recombination only in T cells

increased double-negative T cell number ( J:114948 )

• similar to mice with recombination only in T cells

enlarged lymph nodes ( J:114948 )

• similar to mice with recombination only in T cells

hematopoietic system

enlarged spleen ( J:114948 )

• similar to mice with recombination only in T cells

increased double-negative T cell number ( J:114948 )

• similar to mice with recombination only in T cells

growth/size/body

enlarged spleen ( J:114948 )

• similar to mice with recombination only in T cells

Genotype
MGI:3690552

cn23

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Fas^lpr/Fas^tm1Cgn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * MRL

immune system

enlarged spleen ( J:114948 )

• 5-fold enlargement

enlarged lymph nodes ( J:114948 )

• 17-fold enlargement in the lymph nodes

• weight of the enlarged lymph nodes is still 200- to 300-fold less than in Fas^tm1.1Cgn Fas^lpr trans-heterozygous mice

hematopoietic system

enlarged spleen ( J:114948 )

• 5-fold enlargement

growth/size/body

enlarged spleen ( J:114948 )

• 5-fold enlargement

Genotype
MGI:3690551

cn24

• Allelic Composition: Fas^lpr/Fas^tm1Cgn; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: C57BL/6 * DBA/2 * MRL

immune system

enlarged spleen ( J:114948 )

• 4 of 5 mice had 2 fold enlargement

increased double-negative T cell number ( J:114948 )

enlarged lymph nodes ( J:114948 )

• 12-fold enlargement in the lymph nodes

• weight of the enlarged lymph nodes is still 200- to 300-fold less than in Fas^tm1.1Cgn Fas^lpr trans-heterozygous mice

hematopoietic system

enlarged spleen ( J:114948 )

• 4 of 5 mice had 2 fold enlargement

increased double-negative T cell number ( J:114948 )

growth/size/body

enlarged spleen ( J:114948 )

• 4 of 5 mice had 2 fold enlargement

Genotype
MGI:3800213

cx25

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Fas^lpr/Fas^lpr
• Genetic Background: B6.Cg-Apoe^tm1Unc Fas^lpr

hematopoietic system

hematopoietic system phenotype ( J:121671 )

N • at 5 months, there are no significant differences in most leukocyte subsets (NK-cells, monocytes/macrophages, and neutrophils) compared to controls

enlarged thymus ( J:121671 )

enlarged spleen ( J:121671 )

• significantly enlarged compared to Apoe-null, Fas-heterozygous mice or Apoe-wt, Fas-homozygous mice at 5 months

decreased CD4-positive, alpha-beta T cell number ( J:121671 )

• numbers of circulating cells are significantly reduced

decreased CD8-positive, alpha-beta T cell number ( J:121671 )

• numbers of circulating cells are significantly reduced comparted to Apoe-wt, Fas-homozygous mice at 5 months

increased IgG level ( J:121671 )

• serum levels of IgG are significantly higher than in Apoe-null and Apoe-null, Fas-heterozygous mice at 6 weeks and at 5 months

growth/size/body

enlarged spleen ( J:121671 )

• significantly enlarged compared to Apoe-null, Fas-heterozygous mice or Apoe-wt, Fas-homozygous mice at 5 months

immune system

enlarged thymus ( J:121671 )

enlarged spleen ( J:121671 )

• significantly enlarged compared to Apoe-null, Fas-heterozygous mice or Apoe-wt, Fas-homozygous mice at 5 months

decreased CD4-positive, alpha-beta T cell number ( J:121671 )

• numbers of circulating cells are significantly reduced

decreased CD8-positive, alpha-beta T cell number ( J:121671 )

• numbers of circulating cells are significantly reduced comparted to Apoe-wt, Fas-homozygous mice at 5 months

increased IgG level ( J:121671 )

• serum levels of IgG are significantly higher than in Apoe-null and Apoe-null, Fas-heterozygous mice at 6 weeks and at 5 months

enlarged lymph nodes ( J:121671 )

decreased autoantibody level ( J:121671 )

• serum antibodies against oxidized phospholipid (OxPL) are decreased compared to Apoe-wt, Fas-homozygous and Apoe-null, Fas-wt controls

increased autoantibody level ( J:121671 )

• levels of IgG anti-cardiolipin antibodies are increased at 5 months relative to controls

• levels of IgG anti-POVPC and anti-PGPC autoantibodies are significantly higher than in controls at 5 months; IgM anti-POVPC levels are increased also

increased anti-double stranded DNA antibody level ( J:121671 )

• serum levels of IgG anti-dsDNA antibodies are significantly higher than in Apoe-null, Fas-wt controls and Apoe-null, Fas-heterozygous mice at 6 weeks and at 5 months

glomerulonephritis ( J:121671 )

• renal damage is observed, with IgG and C3 deposits present in the mesangium and peripheral capillary loops

renal/urinary system

increased kidney apoptosis ( J:121671 )

• at 5 months, renal sections show an increase in apoptotic cells

increased renal tubule apoptosis ( J:121671 )

• increased apoptotic cells are seen in renal tubules at 5 months

increased urine protein level ( J:121671 )

• proteinuria is increased compared to Fas-homozygous controls; proteinuria is not evident at 1 month of age

glomerulonephritis ( J:121671 )

• renal damage is observed, with IgG and C3 deposits present in the mesangium and peripheral capillary loops

increased renal glomerulus lobularity ( J:121671 )

• proliferation of glomerular cells and lobule formation are observed

renal glomerular immunoglobulin deposits ( J:121671 )

• IgG and C3 deposits present in the mesangium and peripheral capillary loops

renal glomerulus hypertrophy ( J:121671 )

• glomerular tuft areas are enlarged compared to controls

cardiovascular system

abnormal aorta morphology ( J:121671 )

• IgG deposition in thickened aortic intimas is seen at 5 months, but is not observed in controls; neglible complement C3 deposition is observed in double homozygotes

atherosclerotic lesions ( J:121671 )

• increased lesion area at aortic valves in mice on a normal chow diet compared to Apoe-null, Fas-wt controls

abnormal vascular endothelial cell morphology ( J:121671 )

• increase in apoptotic cells in vessel walls of heart (in vascular lesions) is observed at 5 months relative to controls

abnormal heart morphology ( J:121671 )

skeleton

decreased bone mineral density ( J:121671 )

• all limbs of female mutants have lower bone mineral densities (BMD) than male mutants at 5 months of age; ostopenia is similar to Apoe-wt, Fas-null mice at 5 months

• femoral BMD is lower in females than controls at 5 months and 9 months; vertebrae BMD shows a similar trend at 5 months and is lower at 9 months

decreased bone mineral density of vertebrae ( J:121671 )

• at 5 months, vertebrae BMD trends to lower values than controls; at 9 months, BMD is significantly lower

decreased bone mineral density of femur ( J:121671 )

• femoral BMD in females is lower than in Apoe-null, Fas-wt controls at 5 months and at 9 months

abnormal trabecular bone morphology ( J:121671 )

• at 9 months, a progressive decrease in trabecular bones (BV/TV, connectivity density, trabecular number, trabecular thickness) is observed in females compared to female Apoe-null, Fas-wt controls

decreased trabecular bone volume ( J:121671 )

decreased bone trabecula number ( J:121671 )

decreased trabecular bone connectivity density ( J:121671 )

decreased trabecular bone thickness ( J:121671 )

homeostasis/metabolism

decreased circulating cholesterol level ( J:121671 )

• total serum cholesterol and unesterified cholesterol levels are lower than Apoe-null, Fas-wt controls

increased urine protein level ( J:121671 )

• proteinuria is increased compared to Fas-homozygous controls; proteinuria is not evident at 1 month of age

cellular

increased kidney apoptosis ( J:121671 )

• at 5 months, renal sections show an increase in apoptotic cells

increased renal tubule apoptosis ( J:121671 )

• increased apoptotic cells are seen in renal tubules at 5 months

endocrine/exocrine glands

enlarged thymus ( J:121671 )

Genotype
MGI:3800656

cx26

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11^tm1.1Ast; Fas^lpr/Fas^lpr
• Genetic Background: B6.Cg-Bcl2l11^tm1.1Ast Fas^lpr

immune system

enlarged spleen ( J:132217 )

• severely enlarged by 16 weeks

spleen hyperplasia ( J:132217 )

increased dendritic cell number ( J:132217 )

• increased in spleen relative to Fas^lpr homozygotes

decreased B cell number ( J:132217 )

• lower in spleen and lymph node compared to wild-type or single mutants

abnormal T cell number ( J:132217 )

• mice show reduced amount of nae T cells compared to wild-type or Bcl2l11-deficient mice

• no difference in number of regulatory T cells is observed

abnormal T cell subpopulation ratio ( J:132217 )

• T cell subpopulations in the spleen and lymph nodes including single-positive, central memory and effector memory T cells are increased compared to single-deficient mice

increased memory T cell number ( J:132217 )

• increased memory T cell numbers in spleen and lymph nodes relative to single mutant animals

increased leukocyte cell number ( J:132217 )

• number of CD45+ cells is increased 4.6-fold vs wild-type, 3.2-fold vs Fas^lpr homozygotes, and 2.8-fold vs Bcl2l11-deficient mice

increased immature B cell number ( J:132217 )

• plasmablast numbers in spleen are increased 30-fold relative to wild-type, 2-fold relative to Bcl2l11-deficient and 4-fold relative to Fas^lpr homozygous mice

increased transitional stage B cell number ( J:132217 )

• number of T1 and T2 B cells is increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased follicular B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased marginal zone B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased macrophage cell number ( J:132217 )

• increased numbers in spleen and lymph nodes are observed

abnormal effector T cell morphology ( J:132217 )

• increased effector memory T cell numbers in spleen and lymph nodes relative to single mutant animals

decreased spleen red pulp amount ( J:132217 )

• enlargement of spleen is accompanied by alteration of spleen architecture, characterized by decreased red pulp amount

increased spleen white pulp amount ( J:132217 )

• enlargement of spleen is accompanied by alteration of spleen architecture, characterized by increased white pulp amount

abnormal splenic cell ratio ( J:132217 )

• T1:follicular B cell ratio is disturbed; ratio is higher significantly higher than wild-type, Bcl2l11-deficient mice or Fas^lpr homozygotes

• increased B cell number; CD19+ B cells are increased by 4.3-fold over wild-type, 1.8-fold over Bcl2l11-null mice and by 3.6-fold over Fas^lpr mice

abnormal lymph node cell ratio ( J:132217 )

• CD19+ B cells are increased 2.2-fold over wild-type and Bcl2l11-deficient mice

• no difference from B cell number in Fas^lpr mice

enlarged lymph nodes ( J:132217 )

• severely enlarged by 16 weeks

lymph node hyperplasia ( J:132217 )

increased susceptibility to autoimmune disorder ( J:132217 )

• on a normally resistant background, mice develop extreme lymphadenopathy and SLE

increased autoantibody level ( J:132217 )

• total anti-IgM and total anti-IgG antibody levels are increased compared to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice; anti-nuclear, anti-cytoplasmic and anti-glomerular antibodies are increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased anti-nuclear antigen antibody level ( J:132217 )

• anti-nuclear antibodies are increased compared to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased anti-double stranded DNA antibody level ( J:132217 )

• anti-dsDNA IgM and IgG antibodies are increased compared to wild-type and Bcl2l11-deficient mice; anti-dsDNA IgM antibody levels are increased over levels in Fas^lpr homozygotes

increased anti-histone antibody level ( J:132217 )

• increased compared to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased anti-single stranded DNA antibody level ( J:132217 )

• anti-ssDNA IgM and IgG antibodies are increased compared to wild-type and Bcl2l11-deficient mice; anti-ssDNA IgM antibody levels are increased over levels in Fas^lpr homozygotes

hematopoietic system

enlarged spleen ( J:132217 )

• severely enlarged by 16 weeks

spleen hyperplasia ( J:132217 )

increased dendritic cell number ( J:132217 )

• increased in spleen relative to Fas^lpr homozygotes

decreased B cell number ( J:132217 )

• lower in spleen and lymph node compared to wild-type or single mutants

abnormal T cell number ( J:132217 )

• mice show reduced amount of nae T cells compared to wild-type or Bcl2l11-deficient mice

• no difference in number of regulatory T cells is observed

abnormal T cell subpopulation ratio ( J:132217 )

• T cell subpopulations in the spleen and lymph nodes including single-positive, central memory and effector memory T cells are increased compared to single-deficient mice

increased memory T cell number ( J:132217 )

• increased memory T cell numbers in spleen and lymph nodes relative to single mutant animals

increased leukocyte cell number ( J:132217 )

• number of CD45+ cells is increased 4.6-fold vs wild-type, 3.2-fold vs Fas^lpr homozygotes, and 2.8-fold vs Bcl2l11-deficient mice

increased immature B cell number ( J:132217 )

• plasmablast numbers in spleen are increased 30-fold relative to wild-type, 2-fold relative to Bcl2l11-deficient and 4-fold relative to Fas^lpr homozygous mice

increased transitional stage B cell number ( J:132217 )

• number of T1 and T2 B cells is increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased follicular B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased marginal zone B cell number ( J:132217 )

• higher in spleen relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased macrophage cell number ( J:132217 )

• increased numbers in spleen and lymph nodes are observed

abnormal effector T cell morphology ( J:132217 )

• increased effector memory T cell numbers in spleen and lymph nodes relative to single mutant animals

decreased spleen red pulp amount ( J:132217 )

• enlargement of spleen is accompanied by alteration of spleen architecture, characterized by decreased red pulp amount

increased spleen white pulp amount ( J:132217 )

• enlargement of spleen is accompanied by alteration of spleen architecture, characterized by increased white pulp amount

abnormal splenic cell ratio ( J:132217 )

• T1:follicular B cell ratio is disturbed; ratio is higher significantly higher than wild-type, Bcl2l11-deficient mice or Fas^lpr homozygotes

• increased B cell number; CD19+ B cells are increased by 4.3-fold over wild-type, 1.8-fold over Bcl2l11-null mice and by 3.6-fold over Fas^lpr mice

renal/urinary system

increased renal glomerulus apoptosis ( J:132217 )

• higher numbers of apoptotic cells are detected in glomeruli compared to wild-type and single mutant mice

increased kidney cell proliferation ( J:132217 )

• glomerular proliferation is increased

abnormal kidney morphology ( J:132217 )

• significant increase in renal B cells (CD19+) compared to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

• number of macrophages surrounding glomeruli is increased compared to wild-type and Fas^lpr homozygotes; macrophage index is 2.5-fold higher than in Fas homozygotes

abnormal renal glomerulus basement membrane morphology ( J:132217 )

• IgG deposits mainly localized to basement glomerular membrane are increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

increased renal glomerulus basement membrane thickness ( J:132217 )

• glomerular basement membrane thickening

abnormal renal glomerulus morphology ( J:132217 )

• mesangial expansion, basement membrane thickening, increased interstitial infiltration, and loss of open capillary loops are characteristic hallmarks of renal damage observed

• kidney damage pathological scores are increased over wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient glomeruli

• glomerular proliferation is increased

abnormal glomerular capillary morphology ( J:132217 )

• loss of open capillary loops

expanded mesangial matrix ( J:132217 )

• mesangial expansion

renal glomerulus hypertrophy ( J:132217 )

• glomerular size is increased relative to wild-type, Fas^lpr homozygotes, and Bcl2l11-deficient mice

cellular

increased renal glomerulus apoptosis ( J:132217 )

• higher numbers of apoptotic cells are detected in glomeruli compared to wild-type and single mutant mice

increased kidney cell proliferation ( J:132217 )

• glomerular proliferation is increased

cardiovascular system

abnormal glomerular capillary morphology ( J:132217 )

• loss of open capillary loops

growth/size/body

enlarged spleen ( J:132217 )

• severely enlarged by 16 weeks

spleen hyperplasia ( J:132217 )

Genotype
MGI:5437713

cx27

• Allelic Composition: Fas^lpr/Fas^lpr; Havcr1^tm1Kuch/Havcr1^tm1Kuch
• Genetic Background: B6.Cg-Havcr1^tm1Kuch Fas^lpr

immune system

enlarged spleen ( J:186484 )

• more severe in mice over 10 months of age compared to mice homozygous for Fas^lpr alone

increased B cell number ( J:186484 )

• massive accumulation of B cells

increased T cell number ( J:186484 )

• increase in the number of B220+CD3+ T cells in the peripheral lymphoid compartments compared to mice homozygous for Fas^lpr alone

increased double-negative T cell number ( J:186484 )

• massive increase in CD3+B220-CD4-CD8- and CD3+B220+CD4-CD8- T cells

increased CD4-positive, alpha-beta T cell number ( J:186484 )

• massive increase in the accumulation of CD3+B220- CD4+ T cells

• increase in the frequency of IFNG+ cells

increased CD8-positive, alpha-beta T cell number ( J:186484 )

• massive increase in the accumulation of CD3+B220- CD8+ T cells

• increase in the frequency of IFNG+ cells

increased activated T cell number ( J:186484 )

• most T cells have an activated/memory like phenotype

abnormal immunoglobulin level ( J:186484 )

• unlike IgG levels, IgM levels are decreased compared to mice homozygous for Fas^lpr alone

increased IgG1 level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

increased IgG2a level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

increased IgG2b level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

increased IgG3 level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

enlarged lymph nodes ( J:186484 )

• more severe in mice over 10 months of age compared to mice homozygous for Fas^lpr alone

increased susceptibility to systemic lupus erythematosus ( J:186484 )

• more severe autoimmune response compared to mice homozygous for Fas^lpr alone

increased autoantibody level ( J:186484 )

• serum levels of some autoantibodies to lupus associated autoantigens are increased at 14 weeks of age in double mutant mice but not in mice homozygous for Fas^lpr alone

• autoantibodies can be detected as early as 10 weeks of age

increased anti-double stranded DNA antibody level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

hematopoietic system

enlarged spleen ( J:186484 )

• more severe in mice over 10 months of age compared to mice homozygous for Fas^lpr alone

increased B cell number ( J:186484 )

• massive accumulation of B cells

increased T cell number ( J:186484 )

• increase in the number of B220+CD3+ T cells in the peripheral lymphoid compartments compared to mice homozygous for Fas^lpr alone

increased double-negative T cell number ( J:186484 )

• massive increase in CD3+B220-CD4-CD8- and CD3+B220+CD4-CD8- T cells

increased CD4-positive, alpha-beta T cell number ( J:186484 )

• massive increase in the accumulation of CD3+B220- CD4+ T cells

• increase in the frequency of IFNG+ cells

increased CD8-positive, alpha-beta T cell number ( J:186484 )

• massive increase in the accumulation of CD3+B220- CD8+ T cells

• increase in the frequency of IFNG+ cells

increased activated T cell number ( J:186484 )

• most T cells have an activated/memory like phenotype

abnormal immunoglobulin level ( J:186484 )

• unlike IgG levels, IgM levels are decreased compared to mice homozygous for Fas^lpr alone

increased IgG1 level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

increased IgG2a level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

increased IgG2b level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

increased IgG3 level ( J:186484 )

• compared to mice homozygous for Fas^lpr alone

growth/size/body

enlarged spleen ( J:186484 )

• more severe in mice over 10 months of age compared to mice homozygous for Fas^lpr alone

Genotype
MGI:4356291

cx28

• Allelic Composition: Fas^lpr/Fas^lpr; Il2ra^tm1Dw/Il2ra^tm1Dw; Tg(CD2-Ccdc86)1Hfuj/?
• Genetic Background: B6.Cg-Il2ra^tm1Dw Fas^lpr Tg(CD2-Ccdc86)1Hfuj

immune system

enlarged spleen ( J:151722 )

• absence of the Fas receptor prevents the transgene from rescuing the splenomegaly associated with Il2ra^tm1Dw homozygotes

hematopoietic system

enlarged spleen ( J:151722 )

• absence of the Fas receptor prevents the transgene from rescuing the splenomegaly associated with Il2ra^tm1Dw homozygotes

growth/size/body

enlarged spleen ( J:151722 )

• absence of the Fas receptor prevents the transgene from rescuing the splenomegaly associated with Il2ra^tm1Dw homozygotes

Genotype
MGI:3799744

cx29

• Allelic Composition: Fas^lpr/Fas^lpr; Tlr9^tm1Aki/Tlr9^tm1Aki
• Genetic Background: B6.Cg-Tlr9^tm1Aki Fas^lpr

mortality/aging

premature death ( J:135036 )

• 66% survival at 24 weeks

hematopoietic system

enlarged spleen ( J:135036 )

• spleens are 5-fold heavier than in MRL/MpJ-Fas^lpr mice

increased double-negative T cell number ( J:135036 )

• dramatically increased compared to wild-type; increased relative to Tlr9 and Fas mutants

increased IgG level ( J:135036 )

• total levels are higher than wild-type or Fas^lpr mice

decreased IgM level ( J:135036 )

• lower than in Fas^lpr mice

immune system

enlarged spleen ( J:135036 )

• spleens are 5-fold heavier than in MRL/MpJ-Fas^lpr mice

increased double-negative T cell number ( J:135036 )

• dramatically increased compared to wild-type; increased relative to Tlr9 and Fas mutants

increased IgG level ( J:135036 )

• total levels are higher than wild-type or Fas^lpr mice

decreased IgM level ( J:135036 )

• lower than in Fas^lpr mice

enlarged lymph nodes ( J:135036 )

• generalized lymphadenopathy

• axillary and inguinal lymph node weights are greater than in Fas^lpr mice (by >5-fold)

autoimmune response ( J:135036 )

• autoantibodies such as anti-ssDNA, anti-dsDNA, anti-cardiolipin, and anti-IgG are detected, and levels are not different from Fas mutants

glomerulonephritis ( J:135036 )

• interstitial lymphoid infiltration is observed at 13 weeks

• mesangial proliferation is greater than in Fas single mutants

homeostasis/metabolism

increased urine protein level ( J:135036 )

• increased more from 13 to 24 weeks than in Fas single mutants but not significantly so

renal/urinary system

increased urine protein level ( J:135036 )

• increased more from 13 to 24 weeks than in Fas single mutants but not significantly so

glomerulonephritis ( J:135036 )

• interstitial lymphoid infiltration is observed at 13 weeks

• mesangial proliferation is greater than in Fas single mutants

renal glomerular immunoglobulin deposits ( J:135036 )

• glomerular IgG deposits that are exclusively mesangial are more severe than in Fas single mutants

growth/size/body

enlarged spleen ( J:135036 )

• spleens are 5-fold heavier than in MRL/MpJ-Fas^lpr mice

Genotype
MGI:3812133

cx30

• Allelic Composition: Dsg4^hage/Dsg4^hage; Fas^lpr/Fas^lpr; X/Yaa
• Genetic Background: EOD-Dsg4^hage

mortality/aging

extended life span ( J:140028 )

♂ • the mean life span of these male mice is 99 days, which is significantly longer than the 88 day mean lifespan that males from this strain normally live

growth/size/body

decreased body size ( J:140028 )

♂ • mice are generally smaller than controls

immune system

abnormal mast cell morphology ( J:140028 )

♂ • increased mast cell numbers are found in the superficial layer of the epidermis, with about a 3-fold increase over controls

abnormal effector T cell morphology ( J:140028 )

♂ • the characteristic B220⁺Thy1⁺ T cells population found in the spleen of mice carrying the Fas^lps allele is reduced by more than 5-fold in these mice

hematopoietic system

abnormal mast cell morphology ( J:140028 )

♂ • increased mast cell numbers are found in the superficial layer of the epidermis, with about a 3-fold increase over controls

abnormal effector T cell morphology ( J:140028 )

♂ • the characteristic B220⁺Thy1⁺ T cells population found in the spleen of mice carrying the Fas^lps allele is reduced by more than 5-fold in these mice

integument

sparse hair ( J:140028 )

♂ • pups have scanty growth of short hair on the head and back

abnormal hair follicle morphology ( J:140028 )

♂ • the number of hair follicles in a given patch of skin appears to be higher than controls but counting is difficult because of the unusual orientation of the follicles

abnormal hair follicle orientation ( J:140028 )

♂ • axes of hair shafts are randomly oriented, with some being horizontal to the skin layer

absent vibrissae ( J:140028 )

♂ • mice fail to grow vibrissae hairs

thick epidermis ( J:140028 )

♂ • mice have thick skin with hyperplasia of the epidermis that is prone to injury

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypotrichosis 6		DOID:0110703	OMIM:607903	J:140028

Genotype
MGI:5006703

cx31

• Allelic Composition: Fas^lpr/Fas^lpr; Fasl^tm2.1Bksa/Fasl^tm2.1Bksa
• Genetic Background: involves: 129 * C57BL/6 * MRL/Mp

vision/eye

vision/eye phenotype ( J:171440 )

N • TNFalpha-treated mice do not exhibit a decrease in retinal nerve fibers like in similarly treated wild-type mice

abnormal retina ganglion cell morphology ( J:171440 )

• after 1 week, TNFalpha-treated mice fail to exhibit a decrease in retinal ganglion cells unlike in similarly treated wild-type mice

nervous system

abnormal retina ganglion cell morphology ( J:171440 )

• after 1 week, TNFalpha-treated mice fail to exhibit a decrease in retinal ganglion cells unlike in similarly treated wild-type mice

Genotype
MGI:4947940

cx32

• Allelic Composition: Fas^lpr/Fas^lpr; Tcra^tm1Mjo/Tcra^tm1Mjo
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * MRL

mortality/aging

extended life span ( J:38492 )

• relative to mutant mice wild-type for Tcra

immune system

decreased immunoglobulin level ( J:38492 )

• lower titers of immunoglobulins, other than IgE, compared to mutant mice wild-type for Tcra

decreased autoantibody level ( J:38492 )

• lower titers autoantibodies compared to mutant mice wild-type for Tcra

integument

skin lesions ( J:38492 )

• development of skin lesions is delayed (develop by 7 to 8 months of age) compared to mutant mice wild-type by Tcra

renal/urinary system

abnormal kidney morphology ( J:38492 )

• substantial reduction in renal disease compared to mutant mice wild-type for Tcra

hematopoietic system

decreased immunoglobulin level ( J:38492 )

• lower titers of immunoglobulins, other than IgE, compared to mutant mice wild-type for Tcra

Genotype
MGI:4947942

cx33

• Allelic Composition: Cd40lg^tm1Flv/Y; Fas^lpr/Fas^lpr
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * MRL

mortality/aging

extended life span ( J:38492 )

♂ • relative to mutant mice wild-type for Cd40lg

immune system

decreased immunoglobulin level ( J:38492 )

♂ • lower titers of immunoglobulins compared to mutant mice wild-type for Cd40lg

decreased IgG level ( J:38492 )

♂ • lower titers of IgG1, IgG2a dna IgG2b compared to mice homozygous for Fas^lpr and Cd40lg^tm1Flv

decreased autoantibody level ( J:38492 )

♂ • lower titers autoantibodies compared to mutant mice wild-type for Cd40lg

integument

alopecia ( J:38492 )

♂ • develop severe hair loss by 24 weeks of age

skin lesions ( J:38492 )

♂ • develop scabs and purpuric lesions of the dorsal neck and ears by 24 weeks of age

renal/urinary system

abnormal kidney morphology ( J:38492 )

♂ • substantial reduction in renal disease compared to mutant mice wild-type for Cd40lg

hematopoietic system

decreased immunoglobulin level ( J:38492 )

♂ • lower titers of immunoglobulins compared to mutant mice wild-type for Cd40lg

decreased IgG level ( J:38492 )

♂ • lower titers of IgG1, IgG2a dna IgG2b compared to mice homozygous for Fas^lpr and Cd40lg^tm1Flv

Genotype
MGI:4947943

cx34

• Allelic Composition: Cd40lg^tm1Flv/Y; Fas^lpr/Fas^lpr; Tcra^tm1Mjo/Tcra^tm1Mjo
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * MRL

immune system

decreased autoantibody level ( J:38492 )

♂ • lower titers autoantibodies compared to mutant mice wild-type for Cd40lg

♂ • decrease in the anti-snRNP and anti-Ig titers relative to mutant mice compared to mutant mice wild-type for Cd40lg

increased anti-double stranded DNA antibody level ( J:38492 )

♂ • relative to mutant mice wild-type for Tcra

integument

integument phenotype ( J:38492 )

♂N • do not develop the skin lesions seen in mutant mice wild-type for Tcra and/or Cd40lg

renal/urinary system

abnormal kidney morphology ( J:38492 )

♂ • renal disease is decreased compared to mutant mice wild-type Cd40lg but more diseased than mutant mice wild-type for Tcra

Genotype
MGI:4947941

cx35

• Allelic Composition: Cd40lg^tm1Flv/Cd40lg^tm1Flv; Fas^lpr/Fas^lpr
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * MRL

mortality/aging

extended life span ( J:38492 )

♀ • relative to mutant mice wild-type for Cd40lg

immune system

decreased immunoglobulin level ( J:38492 )

♀ • lower titers of immunoglobulins compared to mutant mice wild-type for Cd40lg

decreased IgG level ( J:38492 )

♀ • lower titers of IgG1, IgG2a dna IgG2b compared to mice homozygous for Fas^lpr and Cd40lg^tm1Flv

decreased autoantibody level ( J:38492 )

♀ • lower titers autoantibodies compared to mutant mice wild-type for Cd40lg

integument

alopecia ( J:38492 )

♀ • develop severe hair loss by 24 weeks of age

skin lesions ( J:38492 )

♀ • develop scabs and purpuric lesions of the dorsal neck and ears by 24 weeks of age

renal/urinary system

abnormal kidney morphology ( J:38492 )

♀ • substantial reduction in renal disease compared to mutant mice wild-type for Cd40lg

hematopoietic system

decreased immunoglobulin level ( J:38492 )

♀ • lower titers of immunoglobulins compared to mutant mice wild-type for Cd40lg

decreased IgG level ( J:38492 )

♀ • lower titers of IgG1, IgG2a dna IgG2b compared to mice homozygous for Fas^lpr and Cd40lg^tm1Flv

Genotype
MGI:4947944

cx36

• Allelic Composition: Cd40lg^tm1Flv/Cd40lg^tm1Flv; Fas^lpr/Fas^lpr; Tcra^tm1Mjo/Tcra^tm1Mjo
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * MRL

immune system

decreased autoantibody level ( J:38492 )

♀ • lower titers autoantibodies compared to mutant mice wild-type for Cd40lg

♀ • decrease in the anti-snRNP and anti-Ig titers relative to mutant mice compared to mutant mice wild-type for Cd40lg

increased anti-double stranded DNA antibody level ( J:38492 )

♀ • relative to mutant mice wild-type for Tcra

integument

integument phenotype ( J:38492 )

♀N • do not develop the skin lesions seen in mutant mice wild-type for Tcra and/or Cd40lg

renal/urinary system

abnormal kidney morphology ( J:38492 )

♀ • renal disease is decreased compared to mutant mice wild-type Cd40lg but more diseased than mutant mice wild-type for Tcra

Genotype
MGI:4839051

cx37

• Allelic Composition: Fas^lpr/Fas^lpr; Il4^tm1Cgn/Il4^tm1Cgn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * MRL/Mp

immune system

abnormal spleen size ( J:39600 )

• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Il4

enlarged spleen ( J:39600 )

increased spleen weight ( J:39600 )

• relative to wild-type controls but decreased relative to mice homozygous for Fas^lpr and wild-type for Il4

spleen hyperplasia ( J:39600 )

• relative to wild-type controls but decreased relative to mice homozygous for Fas^lpr and wild-type for Il4

decreased immunoglobulin level ( J:39600 )

decreased IgA level ( J:39600 )

• at 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Il4

decreased IgE level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Il4

decreased IgG1 level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Il4

decreased IgG3 level ( J:39600 )

• at 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Il4

abnormal lymph node size ( J:39600 )

• lympadenopathy (based on lymph node weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Il4

decreased susceptibility to systemic lupus erythematosus ( J:39600 )

• while mice develop the typical autoimmune lesions end organ disease is decreased compared to mice homozygous for Fas^lpr and wild-type for Ifng

• incidence of end organ disease is increased compared to wild-type controls

decreased anti-nuclear antigen antibody level ( J:39600 )

• decrease in the percentage of FANA positive sera compared to controls at 3 months of age

• however, no significant differences in anti-dsDNA or anti-snRNP autoantibody levels are detected

homeostasis/metabolism

decreased circulating creatinine level ( J:39600 )

• levels are lower compared to mice homozygous for Fas^lpr and wild-type for Il4

hematopoietic system

abnormal spleen size ( J:39600 )

• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Il4

enlarged spleen ( J:39600 )

increased spleen weight ( J:39600 )

• relative to wild-type controls but decreased relative to mice homozygous for Fas^lpr and wild-type for Il4

spleen hyperplasia ( J:39600 )

• relative to wild-type controls but decreased relative to mice homozygous for Fas^lpr and wild-type for Il4

decreased immunoglobulin level ( J:39600 )

decreased IgA level ( J:39600 )

• at 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Il4

decreased IgE level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Il4

decreased IgG1 level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Il4

decreased IgG3 level ( J:39600 )

• at 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Il4

growth/size/body

enlarged spleen ( J:39600 )

increased spleen weight ( J:39600 )

• relative to wild-type controls but decreased relative to mice homozygous for Fas^lpr and wild-type for Il4

spleen hyperplasia ( J:39600 )

• relative to wild-type controls but decreased relative to mice homozygous for Fas^lpr and wild-type for Il4

Genotype
MGI:3800140

cx38

• Allelic Composition: Fas^lpr/Fas^lpr; Pou2af1^tm1Pmt/Pou2af1^tm1Pmt
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * MRL

mortality/aging

mortality/aging ( J:125114 )

N • at 7 months, all double mutants are still alive compared to extensive mortality observed in Fas single mutants by this age

immune system

decreased plasma cell number ( J:125114 )

• number of splenic IgG-secreting cells is dramatically lower than in Fas single mutants

• number of bone marrow IgG-secreting cells is dramatically lower than in Fas single mutants

increased B cell number ( J:125114 )

• in bone marrow, numbers of CD19+IgM- and CD19+IgD- B cells is increased

abnormal T cell number ( J:125114 )

• accumulation of B220+CD3+ cells in spleens and lymph nodes is markedly reduced compared to Fas single mutants

decreased immunoglobulin level ( J:125114 )

• serum immunoglobulin levels are significantly reduced compared to Fas single mutants and are similar to Pou2af1-null mice

• serum level of IgA is reduced but not to same extent as IgG

• IgM production is decreased

autoimmune response ( J:125114 )

• mice do not develop autoantibodies (anti-dsDNA or any IgG antinuclear autoantibodies)

hematopoietic system

hematopoietic system phenotype ( J:125114 )

N • splenic immature and mature B cell numbers are not reduced (a slight increase is observed)

decreased plasma cell number ( J:125114 )

• number of splenic IgG-secreting cells is dramatically lower than in Fas single mutants

• number of bone marrow IgG-secreting cells is dramatically lower than in Fas single mutants

increased B cell number ( J:125114 )

• in bone marrow, numbers of CD19+IgM- and CD19+IgD- B cells is increased

abnormal T cell number ( J:125114 )

• accumulation of B220+CD3+ cells in spleens and lymph nodes is markedly reduced compared to Fas single mutants

decreased immunoglobulin level ( J:125114 )

• serum immunoglobulin levels are significantly reduced compared to Fas single mutants and are similar to Pou2af1-null mice

• serum level of IgA is reduced but not to same extent as IgG

• IgM production is decreased

renal/urinary system

abnormal renal glomerulus morphology ( J:125114 )

• no IgG or C3 deposition is observed, but crescent formation and enlargement of glomeruli is observed

• no inflammation is observed

glomerular crescent ( J:125114 )

• crescent formation is observed

renal glomerulus hypertrophy ( J:125114 )

• enlargement of glomeruli is observed

Genotype
MGI:4944220

cx39

• Allelic Composition: Fas^lpr/Fas^lpr; Tcra^tm1Mjo/Tcra^tm1Mjo
• Genetic Background: involves: 129P2/OlaHsd * MRL

immune system

immune system phenotype ( J:26250 )

N • unlike in mutant mice wild-type for Tcra, massive lymphadenopathy is not seen at 16 weeks of age

increased T cell number ( J:26250 )

• 6 fold increase in TCRB+ cells compared to mutant mice wild-type for Fas

• within the TCRB+ cell population the proportion of DN B220+ cells is increased compared mutant mice wild-type for Fas

increased gamma-delta T cell number ( J:26250 )

• 15 fold expansion at 16 weeks of age compared to mutant mice wild-type for Fas

• the majority of these cells express B220 and DN as a result of preferential expansion (300 fold) of this population of cells

increased gamma-delta intraepithelial T cell number ( J:26250 )

• increase in the proportion of T cells in the peripheral lymph nodes expressing the gamma delta variable regions typical of intestinal intraepithelial T cell compared to mutant mice wild-type for Fas

kidney inflammation ( J:45448 )

• periglomerular infiltration and perivasculitis

renal/urinary system

increased urine protein level ( J:45448 )

• compared to age-matched B10.A mice

kidney inflammation ( J:45448 )

• periglomerular infiltration and perivasculitis

abnormal kidney morphology ( J:45448 )

• develop glomerular, interstitial and sometimes perivascular lesions

• lesion development is reduced compared mutant mice wild-type for Tcra

abnormal renal glomerulus morphology ( J:45448 )

• focal glomerular hypercellularity

homeostasis/metabolism

increased blood urea nitrogen level ( J:45448 )

• significantly elevated

increased urine protein level ( J:45448 )

• compared to age-matched B10.A mice

hematopoietic system

increased T cell number ( J:26250 )

• 6 fold increase in TCRB+ cells compared to mutant mice wild-type for Fas

• within the TCRB+ cell population the proportion of DN B220+ cells is increased compared mutant mice wild-type for Fas

increased gamma-delta T cell number ( J:26250 )

• 15 fold expansion at 16 weeks of age compared to mutant mice wild-type for Fas

• the majority of these cells express B220 and DN as a result of preferential expansion (300 fold) of this population of cells

increased gamma-delta intraepithelial T cell number ( J:26250 )

• increase in the proportion of T cells in the peripheral lymph nodes expressing the gamma delta variable regions typical of intestinal intraepithelial T cell compared to mutant mice wild-type for Fas

Genotype
MGI:5478501

cx40

• Allelic Composition: Fas^lpr/Fas^lpr; Tlr7^tm1Flv/Y
• Genetic Background: involves: 129S1/Sv * C57BL/6 * MRL/Mp

immune system

decreased double-negative T cell number ( J:113557 )

♂ • decrease in accumulation of double-negative T cells in the spleen compared to Fas^lpr homozygotes

abnormal CD4-positive, alpha beta T cell morphology ( J:113557 )

♂ • decrease in proportion of CD4+ T cells expressing CD44, both in the lymph node and spleen compared to Fas^lpr homozygotes

decreased spleen weight ( J:113557 )

♂ • spleen weight is decreased compared to Fas^lpr homozygotes

abnormal B cell activation ( J:113557 )

♂ • general B cell activation is inhibited compared to Fas^lpr homozygotes, as indicated by decreased CD44 expression in splenic B cells

decreased IgG2a level ( J:113557 )

♂ • serum IgG2a levels are decreased compared to Fas^lpr homozygotes

decreased IgG3 level ( J:113557 )

♂ • serum IgG3 levels are decreased compared to Fas^lpr homozygotes

abnormal lymph node size ( J:113557 )

♂ • lymph node weight is decreased compared to Fas^lpr homozygotes

abnormal plasmacytoid dendritic cell physiology ( J:113557 )

♂ • plasmacytoid DCs exhibit a more immature phenotype compared to Fas^lpr homozygotes, with decreased expression of MHC class II

decreased susceptibility to systemic lupus erythematosus ( J:113557 )

♂ • renal disease is significantly decreased compared to Fas^lpr homozygotes, with mice showing decreased glomerular protein deposition and preserved glomerular structure

♂ • although skin disease is evident in mutants, it occurs with a very low frequency and very little is seen at 16 weeks of age

decreased autoantibody level ( J:113557 )

♂ • mutants exhibit impaired generation of antibodies to RNA complexes and generation of high-titer Smith antibodies is blocked

increased autoantibody level ( J:113557 )

♂ • DNA autoantibodies are seen in mutants

increased anti-chromatin antibody level ( J:113557 )

♂

hematopoietic system

decreased double-negative T cell number ( J:113557 )

♂ • decrease in accumulation of double-negative T cells in the spleen compared to Fas^lpr homozygotes

abnormal CD4-positive, alpha beta T cell morphology ( J:113557 )

♂ • decrease in proportion of CD4+ T cells expressing CD44, both in the lymph node and spleen compared to Fas^lpr homozygotes

decreased spleen weight ( J:113557 )

♂ • spleen weight is decreased compared to Fas^lpr homozygotes

abnormal B cell activation ( J:113557 )

♂ • general B cell activation is inhibited compared to Fas^lpr homozygotes, as indicated by decreased CD44 expression in splenic B cells

decreased IgG2a level ( J:113557 )

♂ • serum IgG2a levels are decreased compared to Fas^lpr homozygotes

decreased IgG3 level ( J:113557 )

♂ • serum IgG3 levels are decreased compared to Fas^lpr homozygotes

Genotype
MGI:3767451

cx41

• Allelic Composition: Fas^lpr/Fas^lpr; Ighm^tm1Cgn/Ighm^tm1Cgn
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * MRL/Mp

immune system

arrested B cell differentiation ( J:119584 )

• a transitional block in early B cell development in evident in bone marrow; pre-B cells are decreased in number

decreased mature B cell number ( J:119584 )

• number of Ig-positive B cells in spleen are 10- to 20-fold lower than in wild-type or Fas^lpr mice

increased T cell number ( J:119584 )

• cell outgrowth in lymphadenopathy is dominated by Tcrb/B220+ cells

enlarged lymph nodes ( J:119584 )

• at 8-10 weeks of age, mice develop significant lymphadenopathy

abnormal humoral immune response ( J:119584 )

• mice fail to respond to T cell-dependent (OVA) or T cell-independent (dextra) antigenic stimulation and do not produce serum specific antibodies to these antigens

abnormal immunoglobulin level ( J:119584 )

• levels of IgG2a and IgA are elevated compared to wild-type mice; significant levels (up to 10-fold) of serum antibodies have the gamma light chain isotype compared to control

decreased IgM level ( J:119584 )

• levels are much lower than in controls, comparable to Igh-6 single nulls

increased autoantibody level ( J:119584 )

• mice have high titers of chromatin antibodies compared to controls and titer increased with age; anti-cardiolipin antibodies are increased in serum in 40% of double mutants

hematopoietic system

arrested B cell differentiation ( J:119584 )

• a transitional block in early B cell development in evident in bone marrow; pre-B cells are decreased in number

decreased mature B cell number ( J:119584 )

• number of Ig-positive B cells in spleen are 10- to 20-fold lower than in wild-type or Fas^lpr mice

increased T cell number ( J:119584 )

• cell outgrowth in lymphadenopathy is dominated by Tcrb/B220+ cells

abnormal immunoglobulin level ( J:119584 )

• levels of IgG2a and IgA are elevated compared to wild-type mice; significant levels (up to 10-fold) of serum antibodies have the gamma light chain isotype compared to control

decreased IgM level ( J:119584 )

• levels are much lower than in controls, comparable to Igh-6 single nulls

homeostasis/metabolism

increased urine protein level ( J:119584 )

• mice show significant proteinuria

renal/urinary system

increased urine protein level ( J:119584 )

• mice show significant proteinuria

Genotype
MGI:3640320

cx42

• Allelic Composition: Dntt^tm1Gfn/Dntt^tm1Gfn; Fas^lpr/Fas^lpr
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * MRL/MpJ

immune system

decreased autoantibody level ( J:110248 )

• significantly lower sera anti-DNA and rheumatoid factor activity than control

Genotype
MGI:3800669

cx43

• Allelic Composition: C3^tm1Crr/C3^tm1Crr; Fas^lpr/Fas^lpr
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * MRL

immune system

immune system phenotype ( J:127292 )

N • mutant and Fas^lpr spleens and lymph nodes do not significantly differ in weight at 10 or 13 weeks; at 17 weeks, LN mass is elevated but not significantly

N • lack of autoantibodies (ANA, anti-dsDNA) is observed

decreased susceptibility to autoimmune disorder ( J:127292 )

renal/urinary system

abnormal renal glomerulus morphology ( J:127292 )

• pathology score is minimally increased relative to B6.MRL-Fas^lpr mutants, but no IgG deposition is observed in kidneys

Genotype
MGI:3800668

cx44

• Allelic Composition: C4b^tm1Crr/C4b^tm1Crr; Fas^lpr/Fas^lpr
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * MRL

immune system

enlarged spleen ( J:127292 )

• spleen mass is significantly increased relative to C3 /Fas^lpr or single Fas^lpr mutants at 17 weeks of age

enlarged cervical lymph nodes ( J:127292 )

• lymph node mass is increased relative to C3-null, Fas^lpr or single Fas^lpr mutants at 13 and 17 weeks of age

abnormal immune system physiology ( J:127292 )

• frequency of antibody-secreting cells (ASCs) or antibody-forming cells (AFCs) is significantly increased in spleen and bone marrow compared to C3-deficient Fas mutants

increased anti-nuclear antigen antibody level ( J:127292 )

• titers of serum ANA are significantly increased at 10, 13, and 17 weeks

increased anti-double stranded DNA antibody level ( J:127292 )

• anti-dsDNA titers are elevated significantly at 17 weeks

hematopoietic system

enlarged spleen ( J:127292 )

• spleen mass is significantly increased relative to C3 /Fas^lpr or single Fas^lpr mutants at 17 weeks of age

renal/urinary system

abnormal kidney morphology ( J:127292 )

• increased IgG deposition relative to C3/Fas mutants is observed in kidney sections

abnormal renal glomerulus morphology ( J:127292 )

• more severe glomerular abnormalities are observed relative to C3/Fas mutants

growth/size/body

enlarged spleen ( J:127292 )

• spleen mass is significantly increased relative to C3 /Fas^lpr or single Fas^lpr mutants at 17 weeks of age

Genotype
MGI:3800670

cx45

• Allelic Composition: C3^tm1Crr/C3^tm1Crr; C4b^tm1Crr/C4b^tm1Crr; Fas^lpr/Fas^lpr
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * MRL

immune system

enlarged spleen ( J:127292 )

• spleen mass is significantly increased relative to C3-null, Fas^lpr or single Fas^lpr mutants at 17 weeks of age

enlarged cervical lymph nodes ( J:127292 )

• lymph node mass is increased relative to C3-null, Fas^lpr or single Fas^lpr mutants at 10 and 13 weeks of age

abnormal immune system physiology ( J:127292 )

• frequency of antibody-secreting cells (ASCs) or antibody-forming cells (AFCs) is significantly increased in spleen, bone marrow, and lymph nodes compared to C3-deficient Fas mutants or single Fas^lpr mutants

increased anti-nuclear antigen antibody level ( J:127292 )

• titers of serum ANA are significantly increased at 10 and 17 weeks, compared to single-deficient mice

increased anti-double stranded DNA antibody level ( J:127292 )

• anti-dsDNA titers are elevated significantly relative to C4, Fas double mutants

hematopoietic system

enlarged spleen ( J:127292 )

• spleen mass is significantly increased relative to C3-null, Fas^lpr or single Fas^lpr mutants at 17 weeks of age

renal/urinary system

abnormal kidney morphology ( J:127292 )

• increased IgG deposition relative to C3/Fas mutants is observed in kidney sections; deposition is similar to C4/Fas mutants

abnormal renal glomerulus morphology ( J:127292 )

• more severe glomerular abnormalities are observed relative to C3/Fas mutants, and pathology is similar to that of C4/Fas double mutants

growth/size/body

enlarged spleen ( J:127292 )

• spleen mass is significantly increased relative to C3-null, Fas^lpr or single Fas^lpr mutants at 17 weeks of age

Genotype
MGI:5552962

cx46

• Allelic Composition: Fas^lpr/Fas^lpr; Itfg2^{Gt(OST215121)Lex}/Itfg2^{Gt(OST215121)Lex}
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6J * MRL/Mp

immune system

enlarged spleen ( J:205951 )

• worse than in Fas^lpr homozygotes

increased double-negative T cell number ( J:205951 )

• increased faster in the blood and to a higher proportion than in Fas^lpr homozygotes

decreased B cell number ( J:205951 )

• decreased circulating B cells for the first 13 weeks of age compared with Fas^lpr homozygotes

increased IgG2a level ( J:205951 )

• from 19 weeks compared with Fas^lpr homozygotes

increased IgM level ( J:205951 )

• from 19 weeks compared with Fas^lpr homozygotes

enlarged lymph nodes ( J:205951 )

• worse than in Fas^lpr homozygotes

increased susceptibility to systemic lupus erythematosus ( J:205951 )

• more severe autoimmune disease development with inflammatory cell infiltration of the kidney and hypertrophy in the lymphoid organs compared with Fas^lpr homozygotes

increased anti-nuclear antigen antibody level ( J:205951 )

• compared with Fas^lpr homozygotes

increased anti-double stranded DNA antibody level ( J:205951 )

• compared with Fas^lpr homozygotes

homeostasis/metabolism

increased urine protein level ( J:205951 )

• compared with Fas^lpr homozygotes

renal/urinary system

increased urine protein level ( J:205951 )

• compared with Fas^lpr homozygotes

hematopoietic system

enlarged spleen ( J:205951 )

• worse than in Fas^lpr homozygotes

increased double-negative T cell number ( J:205951 )

• increased faster in the blood and to a higher proportion than in Fas^lpr homozygotes

decreased B cell number ( J:205951 )

• decreased circulating B cells for the first 13 weeks of age compared with Fas^lpr homozygotes

increased IgG2a level ( J:205951 )

• from 19 weeks compared with Fas^lpr homozygotes

increased IgM level ( J:205951 )

• from 19 weeks compared with Fas^lpr homozygotes

growth/size/body

enlarged spleen ( J:205951 )

• worse than in Fas^lpr homozygotes

Genotype
MGI:4361838

cx47

• Allelic Composition: Fas^lpr/Fas^lpr; Spp1^tm1Rit/Spp1^tm1Rit
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * MRL/Mp

immune system

enlarged spleen ( J:73396 )

• at day 175 compared with wild-type mice with further increase at day 275 compared with Fas^lpr homozygotes

increased IgA level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgA levels are normal unlike in Fas^lpr homozygotes

increased IgG1 level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG1 levels are normal unlike in Fas^lpr homozygotes

increased IgG2a level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG2a levels are normal unlike in Fas^lpr homozygotes

increased IgG2b level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG2b levels are normal unlike in Fas^lpr homozygotes

increased IgG3 level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG3 levels are normal unlike in Fas^lpr homozygotes

increased IgM level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgM levels are normal unlike in Fas^lpr homozygotes

lymph node hyperplasia ( J:73396 )

• at day 175 compared with wild-type mice with further increase at day 275 compared with Fas^lpr homozygotes

increased anti-double stranded DNA antibody level ( J:73396 )

• at day 275

increased anti-single stranded DNA antibody level ( J:73396 )

• at day 275

kidney inflammation ( J:73396 )

• mice exhibit moderate nephritis that worsens from day 175 to 215 unlike either single homozygote

renal/urinary system

kidney inflammation ( J:73396 )

• mice exhibit moderate nephritis that worsens from day 175 to 215 unlike either single homozygote

hematopoietic system

enlarged spleen ( J:73396 )

• at day 175 compared with wild-type mice with further increase at day 275 compared with Fas^lpr homozygotes

increased IgA level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgA levels are normal unlike in Fas^lpr homozygotes

increased IgG1 level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG1 levels are normal unlike in Fas^lpr homozygotes

increased IgG2a level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG2a levels are normal unlike in Fas^lpr homozygotes

increased IgG2b level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG2b levels are normal unlike in Fas^lpr homozygotes

increased IgG3 level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgG3 levels are normal unlike in Fas^lpr homozygotes

increased IgM level ( J:73396 )

• at day 275 compared with wild-type mice

• however, at day 175 IgM levels are normal unlike in Fas^lpr homozygotes

growth/size/body

enlarged spleen ( J:73396 )

• at day 175 compared with wild-type mice with further increase at day 275 compared with Fas^lpr homozygotes

Genotype
MGI:4839049

cx48

• Allelic Composition: Fas^lpr/Fas^lpr; Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: involves: 129S7/SvEvBrd * DBA/1 * MRL/Mp

immune system

decreased double-negative T cell number ( J:39600 )

• decrease in the number of CD4-CD8-B220+ alpha beta T cells compared to mice homozygous for Fas^lpr and wild-type for Ifng

abnormal spleen size ( J:39600 )

• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Ifng

enlarged spleen ( J:39600 )

• at 7-8 months of age a modest increase in spleen size and cellularity is seen relative to wild-type controls

decreased immunoglobulin level ( J:39600 )

decreased IgA level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgG2a level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgG2b level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgM level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

abnormal lymph node size ( J:39600 )

• lympadenopathy (based on lymph node weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Ifng

• in young animals lymph node size is similar to wild-type controls

enlarged lymph nodes ( J:39600 )

• at 7-8 months of age a modest increase in lymph node size and cellularity is seen relative to wild-type controls

decreased susceptibility to systemic lupus erythematosus ( J:39600 )

• while mice develop the typical autoimmune lesions, end organ disease is decreased compared to mice homozygous for Fas^lpr and wild-type for Ifng

decreased autoantibody level ( J:39600 )

• lower titers of anti-snRNP and anti-rheumatoid factors antibodies relative to mice homozygous for Fas^lpr and wild-type for Ifng at 3 and 7-8 months of age

decreased anti-nuclear antigen antibody level ( J:39600 )

• at 3 and 7-8 months of age

decreased anti-double stranded DNA antibody level ( J:39600 )

• at 3 and 7-8 months of age

homeostasis/metabolism

decreased circulating creatinine level ( J:39600 )

• levels are lower compared to mice homozygous for Fas^lpr and wild-type for Ifng

hematopoietic system

decreased double-negative T cell number ( J:39600 )

• decrease in the number of CD4-CD8-B220+ alpha beta T cells compared to mice homozygous for Fas^lpr and wild-type for Ifng

abnormal spleen size ( J:39600 )

• lympadenopathy (based on spleen weight and cellularity) is reduced compared to mice homozygous for Fas^lpr and wild-type for Ifng

enlarged spleen ( J:39600 )

• at 7-8 months of age a modest increase in spleen size and cellularity is seen relative to wild-type controls

decreased immunoglobulin level ( J:39600 )

decreased IgA level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgG2a level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgG2b level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

decreased IgM level ( J:39600 )

• at 3 and 7-8 months of age relative to mice homozygous for Fas^lpr and wild-type for Ifng

growth/size/body

enlarged spleen ( J:39600 )

• at 7-8 months of age a modest increase in spleen size and cellularity is seen relative to wild-type controls

Genotype
MGI:4837859

cx49

• Allelic Composition: Fas^lpr/Fas^lpr; Nos2^tm1Mrl/Nos2^tm1Mrl
• Genetic Background: involves: 129S7/SvEvBrd * MRL

renal/urinary system

abnormal urine homeostasis ( J:42666 )

• protein excretion less than controls at 20 weeks of age but not significantly

decreased urine nitrite level ( J:42666 )

• excrete very low levels of nitrite/nitrate relative to controls, heterozygotes are intermediate

• serum and urine levels of nitrite/nitrate are similar

homeostasis/metabolism

abnormal blood homeostasis ( J:42666 )

• serum and urine levels of nitrite/nitrate are similar

abnormal urine homeostasis ( J:42666 )

• protein excretion less than controls at 20 weeks of age but not significantly

decreased urine nitrite level ( J:42666 )

• excrete very low levels of nitrite/nitrate relative to controls, heterozygotes are intermediate

• serum and urine levels of nitrite/nitrate are similar

immune system

immune system phenotype ( J:42666 )

N • vasculitis absent in renal vessels, unlike controls

N • anti-DNA levels similar to controls

abnormal immunoglobulin level ( J:42666 )

• IgG1/IgG3 ratio is higher than controls

decreased IgG level ( J:42666 )

• significantly reduced rheumatoid factor specific IgG antibodies

decreased IgM level ( J:42666 )

• significantly reduced rheumatoid factor specific IgM antibodies

hematopoietic system

abnormal immunoglobulin level ( J:42666 )

• IgG1/IgG3 ratio is higher than controls

decreased IgG level ( J:42666 )

• significantly reduced rheumatoid factor specific IgG antibodies

decreased IgM level ( J:42666 )

• significantly reduced rheumatoid factor specific IgM antibodies

Genotype
MGI:3053737

cx50

• Allelic Composition: Fas^lpr/Fas^lpr; Tnfrsf1a^tm1.1Gkl/Tnfrsf1a^tm1.1Gkl
• Genetic Background: involves: 129/Sv * C57BL/6

immune system

liver inflammation ( J:92470 )

• liver inflammation is seen by 3-4 weeks of age and persists throughout adulthood

• no change in the severity of liver inflammation is seen compared to Tnfrsf1a^tm1Gkl in homozygotes

liver/biliary system

liver inflammation ( J:92470 )

• liver inflammation is seen by 3-4 weeks of age and persists throughout adulthood

• no change in the severity of liver inflammation is seen compared to Tnfrsf1a^tm1Gkl in homozygotes

Genotype
MGI:3799535

cx51

• Allelic Composition: Fas^lpr/Fas^lpr; Raf1^tm1Bacc/Raf1^tm1Bacc
• Genetic Background: involves: 129/SvHsd * 129P2/OlaHsd * C57BL/6 * MRL

hematopoietic system

abnormal erythropoiesis ( J:135681 )

• differentiation of erythroblasts is blocked even at 60 hours after induction of differentiation, as measured by cell proliferation, volume decrease, and hemoglobin accumulation

cellular

increased apoptosis ( J:135681 )

• number of apoptotic erthroblasts is increased under 10U/ml of erythropoietin

Genotype
MGI:3799536

cx52

• Allelic Composition: Fas^lpr/Fas⁺; Raf1^tm1Bacc/Raf1⁺
• Genetic Background: involves: 129/SvHsd * 129P2/OlaHsd * C57BL/6 * MRL

hematopoietic system

hematopoietic system phenotype ( J:135681 )

N • differentiation of erythroblasts from double heterozygotes is indistinguishable from wild-type cells

Genotype
MGI:3799534

cx53

• Allelic Composition: Fas^lpr/Fas⁺; Raf1^tm1Bacc/Raf1^tm1Bacc
• Genetic Background: involves: 129/SvHsd * 129P2/OlaHsd * C57BL/6 * MRL

mortality/aging

mortality/aging ( J:135681 )

N • introduction of a Fas^lpr allele onto the Raf1-null background rescues the lethality shown by the homozygous Raf1-null embryos

hematopoietic system

hematopoietic system phenotype ( J:135681 )

N • introduction of a Fas^lpr allele onto the Raf1-null background rescues the anemia observed in homozygous Raf1-null embryos

abnormal erythropoiesis ( J:135681 )

• differentiation of erythroblasts is delayed, restoring differentiation to level of Raf1 heterozygotes; differentiation is slower than observed in Raf1-null cells

Genotype
MGI:5563354

cx54

• Allelic Composition: Cd72^b/Cd72^b; Fas^lpr/Fas^lpr
• Genetic Background: involves: C57BL/6 * C57BL/6JJmsSlc * MRL/Mp

immune system

abnormal B cell number ( J:204782 )

• increased percentage of total B cells in the spleen compared with Fas^lpr homozygotes on a MRL background

abnormal T cell number ( J:204782 )

• reduced percentage of lpr T cells in the spleen compared with Fas^lpr homozygotes on a MRL background

• increased percentage of total T cells in the spleen compared with Fas^lpr homozygotes on a MRL background

decreased spleen weight ( J:204782 )

• compared with Fas^lpr homozygotes on a MRL background

decreased IgG level ( J:204782 )

• compared with Fas^lpr homozygotes on a MRL background

autoimmune response ( J:204782 )

decreased susceptibility to autoimmune disorder ( J:204782 )

• less severe autoimmune disease (reduced spleen weight, reduced percentage of lpr T cells in the spleen, decreased nuclear autoantibodies, reduced glomeruli size, reduced grade of proteinuria and reduced immune complex deposition) compared with Fas^lpr homozygotes on a MRL background

• however, severity of renal disease is the same as in Fas^lpr homozygotes on a MRL background

decreased anti-nuclear antigen antibody level ( J:204782 )

• anti-double- and single-stranded autoantibodies compared with Fas^lpr homozygotes on a MRL background

decreased anti-double stranded DNA antibody level ( J:204782 )

• compared with Fas^lpr homozygotes on a MRL background

renal/urinary system

abnormal urine protein level ( J:204782 )

• reduced proteinuria compared with Fas^lpr homozygotes on a MRL background

abnormal renal glomerulus morphology ( J:204782 )

• decreased size and immune complex deposition compared with Fas^lpr homozygotes on a MRL background

renal glomerular protein deposits ( J:204782 )

homeostasis/metabolism

abnormal urine protein level ( J:204782 )

• reduced proteinuria compared with Fas^lpr homozygotes on a MRL background

hematopoietic system

abnormal B cell number ( J:204782 )

• increased percentage of total B cells in the spleen compared with Fas^lpr homozygotes on a MRL background

abnormal T cell number ( J:204782 )

• reduced percentage of lpr T cells in the spleen compared with Fas^lpr homozygotes on a MRL background

• increased percentage of total T cells in the spleen compared with Fas^lpr homozygotes on a MRL background

decreased spleen weight ( J:204782 )

• compared with Fas^lpr homozygotes on a MRL background

decreased IgG level ( J:204782 )

• compared with Fas^lpr homozygotes on a MRL background

Genotype
MGI:5563353

cx55

• Allelic Composition: Cd72^c/Cd72^c; Fas^lpr/Fas^lpr
• Genetic Background: involves: C57BL/6 * C57BL/6JJmsSlc * MRL/Mp

immune system

increased spleen weight ( J:204782 )

• at 12 months compared with Fas^lpr homozygotes on a C57BL/6 background

abnormal B cell number ( J:204782 )

• reduced percentage compared with Fas^lpr homozygotes on a C57BL/6 background

abnormal T cell number ( J:204782 )

• increased percentage compared with Fas^lpr homozygotes on a C57BL/6 background

• however, the percentage of B220+CD3+ T cells is the same as in Fas^lpr homozygotes on a C57BL/6 background

increased IgG level ( J:204782 )

• compared with Fas^lpr homozygotes on a C57BL/6 background

enlarged lymph nodes ( J:204782 )

• moderate at 12 months compared with Fas^lpr homozygotes on a C57BL/6 background

autoimmune response ( J:204782 )

increased susceptibility to systemic lupus erythematosus ( J:204782 )

• more severe lupus-like disease (greater increase in spleen weight, lymphadenopathy, reduced percentage of B cells, increased percentage of T cells, increased inflammation in the lungs and liver, more severe glomerular lesions and increased nuclear autoantibodies) compared with Fas^lpr homozygotes on a C57BL/6 background

increased anti-chromatin antibody level ( J:204782 )

• at 12 months compared with Fas^lpr homozygotes on a C57BL/6 background

increased anti-double stranded DNA antibody level ( J:204782 )

increased anti-single stranded DNA antibody level ( J:204782 )

• at 12 months compared with Fas^lpr homozygotes on a C57BL/6 background

• however, levels are lower than in Fas^lpr homozygotes on an MRL background

liver inflammation ( J:204782 )

• mice exhibit more severe cell infiltration in the lung and liver compared with Fas^lpr homozygotes on a C57BL/6 background

lung inflammation ( J:204782 )

• mice exhibit more severe cell infiltration in the lung and liver compared with Fas^lpr homozygotes on a C57BL/6 background

renal/urinary system

cortical renal glomerulopathies ( J:204782 )

• more severe glomerular lesions with more prominent immune complex deposition compared with Fas^lpr homozygotes on a C57BL/6 background

liver/biliary system

liver inflammation ( J:204782 )

• mice exhibit more severe cell infiltration in the lung and liver compared with Fas^lpr homozygotes on a C57BL/6 background

respiratory system

lung inflammation ( J:204782 )

• mice exhibit more severe cell infiltration in the lung and liver compared with Fas^lpr homozygotes on a C57BL/6 background

hematopoietic system

increased spleen weight ( J:204782 )

• at 12 months compared with Fas^lpr homozygotes on a C57BL/6 background

abnormal B cell number ( J:204782 )

• reduced percentage compared with Fas^lpr homozygotes on a C57BL/6 background

abnormal T cell number ( J:204782 )

• increased percentage compared with Fas^lpr homozygotes on a C57BL/6 background

• however, the percentage of B220+CD3+ T cells is the same as in Fas^lpr homozygotes on a C57BL/6 background

increased IgG level ( J:204782 )

• compared with Fas^lpr homozygotes on a C57BL/6 background

growth/size/body

increased spleen weight ( J:204782 )

• at 12 months compared with Fas^lpr homozygotes on a C57BL/6 background

Genotype
MGI:3662636

cx56

• Allelic Composition: Fas^lpr/Fas^lpr; Tg(H2-K-Cd86)27All/0
• Genetic Background: involves: C57BL/6 * CBA * MRL/MpJ

hematopoietic system

decreased B cell number ( J:112475 )

• frequency and absolute number of B lymphocytes in primary and secondary lymphoid organs are very low

immune system

decreased B cell number ( J:112475 )

• frequency and absolute number of B lymphocytes in primary and secondary lymphoid organs are very low

Genotype
MGI:5563351

cx57

• Allelic Composition: Cd72^tm1Tsub/Cd72^tm1Tsub; Fas^lpr/Fas^lpr
• Genetic Background: involves: C57BL/6J * C57BL/6JJmsSlc * MRL/Mp

immune system

increased spleen weight ( J:204782 )

• severe at 6 months

abnormal B cell number ( J:204782 )

• reduced percentage total B cells

abnormal T cell number ( J:204782 )

• marked increased percentage of lpr T cells in the spleen, lymph nodes and peritoneal cavity

• increased percentage of total T cells

enlarged lymph nodes ( J:204782 )

• severe at 6 months

autoimmune response ( J:204782 )

increased anti-chromatin antibody level ( J:204782 )

increased anti-double stranded DNA antibody level ( J:204782 )

• more so than in Cd72^tm1Tsub homozygotes

increased anti-single stranded DNA antibody level ( J:204782 )

• more so than in Cd72^tm1Tsub homozygotes

liver inflammation ( J:204782 )

• more so than in either single homozygotes

glomerulonephritis ( J:204782 )

• with immune complex deposition, more so than in either single homozygotes

lung inflammation ( J:204782 )

• more so than in either single homozygotes

renal/urinary system

glomerulonephritis ( J:204782 )

• with immune complex deposition, more so than in either single homozygotes

renal glomerular immunoglobulin deposits ( J:204782 )

liver/biliary system

liver inflammation ( J:204782 )

• more so than in either single homozygotes

respiratory system

lung inflammation ( J:204782 )

• more so than in either single homozygotes

hematopoietic system

increased spleen weight ( J:204782 )

• severe at 6 months

abnormal B cell number ( J:204782 )

• reduced percentage total B cells

abnormal T cell number ( J:204782 )

• marked increased percentage of lpr T cells in the spleen, lymph nodes and peritoneal cavity

• increased percentage of total T cells

growth/size/body

increased spleen weight ( J:204782 )

• severe at 6 months

Genotype
MGI:5689998

cx58

• Allelic Composition: Fas^lpr/Fas^lpr; Kdelr1^m1Btlr/Kdelr1^m1Btlr
• Genetic Background: involves: C57BL/6J * MRL/Mp

immune system

immune system phenotype ( J:224970 )

N • T cell numbers are restored compared to in Kdelr1^m1Btlr homozygotes

Genotype
MGI:5292731

cx59

• Allelic Composition: Fas^lpr/Fas⁺; Tg(TcraTcrb)1100Mjb/?
• Genetic Background: involves: C57BL/6 * MRL/Mp

mortality/aging

mortality/aging ( J:72817 )

N • after administration of OVA peptide 257-264 has no affect on mortality

liver/biliary system

liver/biliary system phenotype ( J:72817 )

N • no morphological abnormalities or increased apoptosis after administration of OVA peptide 257-264

liver inflammation ( J:72817 )

• extensive infiltration of Valpha2⁺ CD8⁺ lymphocytes after administration of OVA peptide 257-264

immune system

liver inflammation ( J:72817 )

• extensive infiltration of Valpha2⁺ CD8⁺ lymphocytes after administration of OVA peptide 257-264

Genotype
MGI:3799494

cx60

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Fas^lpr/Fas^lpr
• Genetic Background: MRL.Cg-Apoe^tm1Unc Fas^lpr

immune system

increased immunoglobulin level ( J:133606 )

• mice display greatly increased levels compared to wild-type controls or Apoe-null mice

increased susceptibility to systemic lupus erythematosus ( J:133606 )

increased autoantibody level ( J:133606 )

• IgG and IgM anti-oxidized LDL and anti-cardiolipin antibodies are increased compared to controls

increased anti-nuclear antigen antibody level ( J:133606 )

• mice display greatly increased levels compared to wild-type controls or Apoe-null mice

increased anti-double stranded DNA antibody level ( J:133606 )

• mice display greatly increased levels compared to wild-type controls or Apoe-null mice

homeostasis/metabolism

increased circulating cholesterol level ( J:133606 )

• significantly increased relative to wild-type controls at 24 weeks of age or Fas-single mutants

cardiovascular system

increased susceptibility to atherosclerosis ( J:133606 )

• modest increase in total area of lipid deposits in aorta compared to Apoe-null mice

hematopoietic system

increased immunoglobulin level ( J:133606 )

• mice display greatly increased levels compared to wild-type controls or Apoe-null mice

Genotype
MGI:3665495

cx61

• Allelic Composition: Ccr2^tm1Blck/Ccr2^tm1Blck; Fas^lpr/Fas^lpr
• Genetic Background: MRL.Cg-Ccr2^tm1Blck Fas^lpr

mortality/aging

premature death ( J:113343 )

• life span is considerably reduced on average but considerably longer than Fas^lpr controls

immune system

abnormal lymphocyte cell number ( J:113343 )

• frequency of CD4+ T cells in peripheral blood is significantly reduced relative to Fas^lpr controls

• percentage of CD8+ T cells is markedly reduced at 14 and 20 weeks of age relative to Fas^lpr controls

abnormal interferon level ( J:113343 )

• levels significantly reduced relative to Fas^lpr controls

abnormal tumor necrosis factor level ( J:113343 )

• levels significantly reduced relative to Fas^lpr controls

abnormal immune system organ morphology ( J:113343 )

enlarged spleen ( J:113343 )

• enlargement is significantly less at 14 weeks of age than in Fas^lpr controls

• spleen enlargement at 20 weeks equivalent to controls

enlarged lymph nodes ( J:113343 )

• enlargement is significantly less than in Fas^lpr controls

kidney inflammation ( J:113343 )

• less T-cell and macrophage infiltration than in Fas^lpr controls

glomerulonephritis ( J:113343 )

• not as extensive as in Fas^lpr controls

renal/urinary system

albuminuria ( J:113343 )

• significantly less developed at 8 and 14 weeks but comparable to Fas^lpr controls at 20 weeks

kidney inflammation ( J:113343 )

• less T-cell and macrophage infiltration than in Fas^lpr controls

glomerulonephritis ( J:113343 )

• not as extensive as in Fas^lpr controls

abnormal renal glomerulus morphology ( J:113343 )

• abnormalities much less than in Fas^lpr controls

• abnormalities seen at 14 weeks of age include hypercellular glomeruli, increased mesangial matrix, and perivascular lymphoid cell accumulations

expanded mesangial matrix ( J:113343 )

• increased mesangial matrix at 14 weeks of age

glomerulosclerosis ( J:113343 )

• intraglomerular necrosis and sclerosis less developed than in Fas^lpr controls

renal tubule atrophy ( J:113343 )

• tubular damage and atrophy less than in Fas^lpr controls

hematopoietic system

enlarged spleen ( J:113343 )

• enlargement is significantly less at 14 weeks of age than in Fas^lpr controls

• spleen enlargement at 20 weeks equivalent to controls

abnormal lymphocyte cell number ( J:113343 )

• frequency of CD4+ T cells in peripheral blood is significantly reduced relative to Fas^lpr controls

• percentage of CD8+ T cells is markedly reduced at 14 and 20 weeks of age relative to Fas^lpr controls

homeostasis/metabolism

abnormal interferon level ( J:113343 )

• levels significantly reduced relative to Fas^lpr controls

abnormal tumor necrosis factor level ( J:113343 )

• levels significantly reduced relative to Fas^lpr controls

albuminuria ( J:113343 )

• significantly less developed at 8 and 14 weeks but comparable to Fas^lpr controls at 20 weeks

growth/size/body

enlarged spleen ( J:113343 )

• enlargement is significantly less at 14 weeks of age than in Fas^lpr controls

• spleen enlargement at 20 weeks equivalent to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:113343

Genotype
MGI:3799683

cx62

• Allelic Composition: Cd180^tm1Kmiy/Cd180^tm1Kmiy; Fas^lpr/Fas^lpr
• Genetic Background: MRL.Cg-Cd180^tm1Kmiy Fas^lpr

mortality/aging

mortality/aging ( J:137066 )

N • Cd180-deficiency ameliorates mortality in Fas^lpr mice; survival to >40 weeks is significantly greater than Fas^lpr homozygotes

hematopoietic system

hematopoietic system phenotype ( J:137066 )

N • numbers of CD4-positive T cells are rescued relative to MRL/MpJ-Fas^lpr

enlarged spleen ( J:137066 )

• severe in double mutants compared to controls, but reduced significantly from that observed in MRL/MpJ-Fas^lpr homozygotes

increased double-negative T cell number ( J:137066 )

• significantly increased relative to controls, similar to MRL/MpJ-Fas^lpr homozygotes

decreased B cell number ( J:137066 )

• CD44+ and CD69+ B cells in spleen are decreased relative to wild-type controls

decreased CD8-positive, alpha-beta T cell number ( J:137066 )

• reduced compared to wild-type controls, but higher than in MRL/MpJ-Fas^lpr homozygotes

decreased IgG2a level ( J:137066 )

• significantly lower in serum at 20 weeks than in MRL/MpJ-Fas^lpr single mutant mice

decreased IgG3 level ( J:137066 )

• significantly reduced in serum at 20 weeks than in MRL/MpJ-Fas^lpr single mutant mice

cardiovascular system

blood vessel inflammation ( J:137066 )

• necrotizing arteritis of small- and medium-sized arteries in kidneys is observed less frequently than in MRL/MpJ-Fas^lpr mice

renal/urinary system

glomerulonephritis ( J:137066 )

immune system

blood vessel inflammation ( J:137066 )

• necrotizing arteritis of small- and medium-sized arteries in kidneys is observed less frequently than in MRL/MpJ-Fas^lpr mice

enlarged spleen ( J:137066 )

• severe in double mutants compared to controls, but reduced significantly from that observed in MRL/MpJ-Fas^lpr homozygotes

increased double-negative T cell number ( J:137066 )

• significantly increased relative to controls, similar to MRL/MpJ-Fas^lpr homozygotes

decreased B cell number ( J:137066 )

• CD44+ and CD69+ B cells in spleen are decreased relative to wild-type controls

decreased CD8-positive, alpha-beta T cell number ( J:137066 )

• reduced compared to wild-type controls, but higher than in MRL/MpJ-Fas^lpr homozygotes

decreased IgG2a level ( J:137066 )

• significantly lower in serum at 20 weeks than in MRL/MpJ-Fas^lpr single mutant mice

decreased IgG3 level ( J:137066 )

• significantly reduced in serum at 20 weeks than in MRL/MpJ-Fas^lpr single mutant mice

enlarged lymph nodes ( J:137066 )

• severe compared to wild-type controls, but reduced significantly from that observed in MRL/MpJ-Fas^lpr homozygotes with largest difference in node size observed in axillary lymph nodes

increased autoantibody level ( J:137066 )

• autoantibody levels are much higher than wild-type controls but no difference is observed in IgG3 anti-IgG2a rheumatoid factor levels compared to MRL/MpJ-Fas^lpr homozygotes

increased anti-nuclear antigen antibody level ( J:137066 )

• levels of anti-dsDNA and anti-chromatin autoantibodies are elevated compared to wild-type, but are similar to MRL/MpJ-Fas^lpr homozygotes

glomerulonephritis ( J:137066 )

homeostasis/metabolism

abnormal blood urea nitrogen level ( J:137066 )

• levels are decreased with Cd180 deficiency, but are still elevated relative to wild-type controls

growth/size/body

enlarged spleen ( J:137066 )

• severe in double mutants compared to controls, but reduced significantly from that observed in MRL/MpJ-Fas^lpr homozygotes

Genotype
MGI:5312683

cx63

• Allelic Composition: Ebi3^tm1Nkma/Ebi3^tm1Nkma; Fas^lpr/Fas^lpr
• Genetic Background: MRL.Cg-Ebi3^tm1Nkma Fas^lpr

mortality/aging

premature death ( J:181669 )

• 90% survival at 20 weeks compared to 50% survival for MRL/lpr controls

renal/urinary system

abnormal glomerular capillary morphology ( J:181669 )

• generalized thickening of the capillary walls

• widespread discrete granular Ig deposition in the capillary walls, primarily IgG1 rather than IgG2a

increased urine protein level ( J:181669 )

• proteinuria increased relative to MRL/lpr controls

abnormal kidney physiology ( J:181669 )

abnormal renal protein reabsorption ( J:181669 )

• proteinuria increased relative to MRL/lpr controls

homeostasis/metabolism

abnormal blood homeostasis ( J:181669 )

decreased circulating creatine level ( J:181669 )

• suppressed relative to MRL/lpr controls

decreased circulating creatinine level ( J:181669 )

• serum creatinine is suppressed relative to MRL/lpr controls

decreased blood urea nitrogen level ( J:181669 )

• suppressed relative to MRL/lpr controls

abnormal cytokine level ( J:181669 )

decreased circulating interferon-gamma level ( J:181669 )

increased circulating interleukin-4 level ( J:181669 )

abnormal renal protein reabsorption ( J:181669 )

• proteinuria increased relative to MRL/lpr controls

increased urine protein level ( J:181669 )

• proteinuria increased relative to MRL/lpr controls

immune system

increased immunoglobulin level ( J:181669 )

increased IgE level ( J:181669 )

increased IgG level ( J:181669 )

increased IgG1 level ( J:181669 )

abnormal cytokine level ( J:181669 )

decreased circulating interferon-gamma level ( J:181669 )

increased circulating interleukin-4 level ( J:181669 )

cardiovascular system

abnormal glomerular capillary morphology ( J:181669 )

• generalized thickening of the capillary walls

• widespread discrete granular Ig deposition in the capillary walls, primarily IgG1 rather than IgG2a

hematopoietic system

increased immunoglobulin level ( J:181669 )

increased IgE level ( J:181669 )

increased IgG level ( J:181669 )

increased IgG1 level ( J:181669 )

Genotype
MGI:3809239

cx64

• Allelic Composition: Fas^lpr/Fas^lpr; Igh-J^{tm2(3H9-VDJ*)Mwg}/Igh-J⁺
• Genetic Background: MRL.Cg-Fas^lpr Igh-J^{tm2(3H9-VDJ*)Mwg}

immune system

abnormal B cell receptor editing ( J:131138 )

• Anti-dsDNA B cells have their transgenic heavy chains paired with kappa light chains that do not prevent DNA binding

• most anti-dsDNA B cells have also edited the heavy chain transgene suggesting de novo development of anti-DNA binding activity

• there is a decrease in the number of unresponsive B cells that express both lamda and kappa chains compared to transgenic mice on a BALB/c background (7.6% of splenic B cells versus to 19.4% )

abnormal marginal zone B cell morphology ( J:131138 )

• mice have a smaller marginal zone B cell population (3.4% of splenic lymphocytes) compared to MRL/lpr mice without the transgene (10.8%)

increased anti-double stranded DNA antibody level ( J:131138 )

• significant levels of IgM and IgG antibodies that bind dsDNA antibodies are detected in mice 6-8 weeks of age

• levels of these auto antibodies rise with age

• the levels of IgG are higher than in age-matched MRL/lpr mice that do not carry the transgene

hematopoietic system

abnormal B cell receptor editing ( J:131138 )

• Anti-dsDNA B cells have their transgenic heavy chains paired with kappa light chains that do not prevent DNA binding

• most anti-dsDNA B cells have also edited the heavy chain transgene suggesting de novo development of anti-DNA binding activity

• there is a decrease in the number of unresponsive B cells that express both lamda and kappa chains compared to transgenic mice on a BALB/c background (7.6% of splenic B cells versus to 19.4% )

abnormal marginal zone B cell morphology ( J:131138 )

• mice have a smaller marginal zone B cell population (3.4% of splenic lymphocytes) compared to MRL/lpr mice without the transgene (10.8%)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:131138

Genotype
MGI:3800459

cx65

• Allelic Composition: Fas^lpr/Fas^lpr; Tg(CD2-Foxj1)#Stlp/0
• Genetic Background: MRL.Cg-Fas^lpr Tg(CD2-Foxj1)#Stlp

immune system

salivary gland inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

enlarged spleen ( J:122222 )

• reduced lymphadenopathy is observed compared to non-transgenic Fas^lpr mice

increased double-negative T cell number ( J:122222 )

• diminished accumulation of CD3+ CD4- CD8- B220+ double negative T cells is observed in peripheral lymphoid organs

decreased CD4-positive, alpha-beta T cell number ( J:122222 )

• peripheral CD4 counts are 8- to 10-fold reduced

abnormal T cell physiology ( J:122222 )

• increased numbers of mature CD4+ thymocytes show defective migration in response to CCL19 in vitro, suggesting impaired ability to emigrate from the thymus

enlarged lymph nodes ( J:122222 )

• reduced lymphadenopathy is observed compared to non-transgenic Fas^lpr mice

decreased susceptibility to systemic lupus erythematosus ( J:122222 )

• double mutant mice display protection against murine lupus (reduced lymphadenopathy, autoantibody production and end-organ disease)

increased anti-nuclear antigen antibody level ( J:122222 )

• anti-DNA autoantibodies are produced; however, these autoantibodies are not high affinity anti-dsDNA antibodies and likely only low affinity anti-ssDNA antibodies are present

liver inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

kidney inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

lung inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

hematopoietic system

enlarged spleen ( J:122222 )

• reduced lymphadenopathy is observed compared to non-transgenic Fas^lpr mice

increased double-negative T cell number ( J:122222 )

• diminished accumulation of CD3+ CD4- CD8- B220+ double negative T cells is observed in peripheral lymphoid organs

decreased CD4-positive, alpha-beta T cell number ( J:122222 )

• peripheral CD4 counts are 8- to 10-fold reduced

abnormal T cell physiology ( J:122222 )

• increased numbers of mature CD4+ thymocytes show defective migration in response to CCL19 in vitro, suggesting impaired ability to emigrate from the thymus

renal/urinary system

kidney inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

endocrine/exocrine glands

salivary gland inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

digestive/alimentary system

salivary gland inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

liver/biliary system

liver inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

respiratory system

lung inflammation ( J:122222 )

• inflammation observed is reduced compared to non-transgenic Fas^lpr mice

growth/size/body

enlarged spleen ( J:122222 )

• reduced lymphadenopathy is observed compared to non-transgenic Fas^lpr mice

Genotype
MGI:4360203

cx66

• Allelic Composition: Fas^lpr/Fas^lpr; Fcer1g^tm1Tks/Fcer1g^tm1Tks
• Genetic Background: MRL.Cg-Fcer1g^tm1Tks Fas^lpr

mortality/aging

premature death ( J:106188 )

• all mice diet of renal failure by 65 weeks of age with a 50% survival rate at a median age of 32-34 weeks similar to MRL-Fas^lpr mice

immune system

immune system phenotype ( J:106188 )

N • MRL-Fas mice homozygous for the Fcer1g^tm1Tks allele still develop glomerulonephritis in a similar manner as MRL-Fas^lpr mice carrying the wild-type Fcer1g^tm1Tks allele

arteritis ( J:106188 )

• necrotizing vasculitis with mononuclear cell infiltration, vessel wall destruction, and occasional thrombosis are observed in the interlobular arteries of the kidney

• necrotizing vasculitis of the pulmonary arteries, with mononuclear cell infiltration and vessel wall destruction occur

increased spleen weight ( J:106188 )

• spleen weight is 7- to 8-fold greater than C57BL/6 controls but is similar to MRL-Fas^lpr mice

increased double-negative T cell number ( J:106188 )

• a double-negative, B220⁺ T cell population accumulates in the spleen and lymph nodes similar to MRL-Fas^lpr mice

increased IgG level ( J:106188 )

• IgG levels are elevated compared to C57BL/6 controls but are similar to MRL-Fas^lpr mice

decreased susceptibility to type III hypersensitivity reaction ( J:106188 )

• extravasation does not occur in mice as occurs in controls when iv injected with OVA and intradermally injected with rabbit anti-OVA IgG

increased anti-double stranded DNA antibody level ( J:106188 )

• anti-DNA Iglevels are elevated compared to C57BL/6 controls but are similar to MRL-Fas^lpr mice

glomerulonephritis ( J:106188 )

• mice develop diffuse proliferative GN with mononuclear cell infiltration, mesangial and endothelial cell proliferation, and crescent formation after 16 weeks of age similar to MRL-Fas^lpr mice

• proteinuria, followed by renal failure, develops in all mice

renal/urinary system

abnormal glomerular capillary endothelium morphology ( J:106188 )

• endothelial cell proliferation is noted after 16 weeks of age

increased mesangial cell number ( J:106188 )

• mesangial cell proliferation is noted after 16 weeks of age

increased kidney cell proliferation ( J:106188 )

• mesangial and endothelial cell proliferation after 16 weeks of age

increased urine protein level ( J:106188 )

• urinary protein concentrations increase with age similar to MRL-Fas^lpr mice

glomerulonephritis ( J:106188 )

• mice develop diffuse proliferative GN with mononuclear cell infiltration, mesangial and endothelial cell proliferation, and crescent formation after 16 weeks of age similar to MRL-Fas^lpr mice

• proteinuria, followed by renal failure, develops in all mice

glomerular crescent ( J:106188 )

• crescent formation is noted after 16 weeks of age

kidney failure ( J:106188 )

• mice die of renal failure by 65 weeks of age similar to MRL-Fas^lpr mice

homeostasis/metabolism

increased urine protein level ( J:106188 )

• urinary protein concentrations increase with age similar to MRL-Fas^lpr mice

cardiovascular system

abnormal glomerular capillary endothelium morphology ( J:106188 )

• endothelial cell proliferation is noted after 16 weeks of age

vascular inflammation ( J:106188 )

• various forms of medium and small vessel vasculitis occur similar to MRL-Fas^lpr mice

arteritis ( J:106188 )

• necrotizing vasculitis with mononuclear cell infiltration, vessel wall destruction, and occasional thrombosis are observed in the interlobular arteries of the kidney

• necrotizing vasculitis of the pulmonary arteries, with mononuclear cell infiltration and vessel wall destruction occur

hematopoietic system

increased spleen weight ( J:106188 )

• spleen weight is 7- to 8-fold greater than C57BL/6 controls but is similar to MRL-Fas^lpr mice

increased double-negative T cell number ( J:106188 )

• a double-negative, B220⁺ T cell population accumulates in the spleen and lymph nodes similar to MRL-Fas^lpr mice

increased IgG level ( J:106188 )

• IgG levels are elevated compared to C57BL/6 controls but are similar to MRL-Fas^lpr mice

cellular

increased mesangial cell number ( J:106188 )

• mesangial cell proliferation is noted after 16 weeks of age

increased kidney cell proliferation ( J:106188 )

• mesangial and endothelial cell proliferation after 16 weeks of age

growth/size/body

increased spleen weight ( J:106188 )

• spleen weight is 7- to 8-fold greater than C57BL/6 controls but is similar to MRL-Fas^lpr mice

Genotype
MGI:4838774

cx67

• Allelic Composition: Fas^lpr/Fas^lpr; Ifnar1^tm1Agt/Ifnar1^tm1Agt
• Genetic Background: MRL.Cg-Ifnar1^tm1Agt Fas^lpr

immune system

salivary gland inflammation ( J:92084 )

• worse than in Fas^lpr homozygotes

increased IgA level ( J:92084 )

• compared with Fas^lpr homozygotes

increased IgG level ( J:92084 )

• mice exhibit IgG deposits in the kidney unlike wild-type mice

increased IgG2b level ( J:92084 )

• compared with Fas^lpr homozygotes

increased IgG3 level ( J:92084 )

• compared with Fas^lpr homozygotes

increased IgM level ( J:92084 )

• compared with Fas^lpr homozygotes

enlarged lymph nodes ( J:92084 )

increased susceptibility to systemic lupus erythematosus ( J:92084 )

• mice exhibit increased serum levels of kappa-chain rheumatoid factor and DNA auto-antibodies, lymphadenopathy, glomerulonephritis, renal immunoglobulin deposits, proteinuria, and end organ disease compared to in wild-type mice

• some systemic lupus erythematosus symptoms are more severe than Fas^lpr homozygotes

increased autoantibody level ( J:92084 )

• mice exhibit increased serum levels of kappa-chain rheumatoid factor compared to in wild-type mice and Fas^lpr homozygotes

increased anti-nuclear antigen antibody level ( J:92084 )

• DNA auto-antibodies are increased compared to in wild-type mice at 12 weeks

glomerulonephritis ( J:92084 )

renal/urinary system

increased urine protein level ( J:92084 )

glomerulonephritis ( J:92084 )

homeostasis/metabolism

increased urine protein level ( J:92084 )

endocrine/exocrine glands

salivary gland inflammation ( J:92084 )

• worse than in Fas^lpr homozygotes

digestive/alimentary system

salivary gland inflammation ( J:92084 )

• worse than in Fas^lpr homozygotes

hematopoietic system

increased IgA level ( J:92084 )

• compared with Fas^lpr homozygotes

increased IgG level ( J:92084 )

• mice exhibit IgG deposits in the kidney unlike wild-type mice

increased IgG2b level ( J:92084 )

• compared with Fas^lpr homozygotes

increased IgG3 level ( J:92084 )

• compared with Fas^lpr homozygotes

increased IgM level ( J:92084 )

• compared with Fas^lpr homozygotes

Genotype
MGI:4838777

cx68

• Allelic Composition: Fas^lpr/Fas^lpr; Ifngr1^tm1Agt/Ifngr1^tm1Agt
• Genetic Background: MRL.Cg-Ifngr1^tm1Agt Fas^lpr

immune system

decreased IgA level ( J:92084 )

• compared with Fas^lpr homozygotes

decreased IgG2a level ( J:92084 )

• compared with Fas^lpr homozygotes

decreased IgG2b level ( J:92084 )

• compared with Fas^lpr homozygotes

decreased IgG3 level ( J:92084 )

• compared with Fas^lpr homozygotes

increased IgG level ( J:92084 )

• some mice exhibit IgG deposits in the kidney unlike wild-type mice

increased IgG1 level ( J:92084 )

• compared with Fas^lpr homozygotes

decreased IgM level ( J:92084 )

• compared with Fas^lpr homozygotes

small lymph nodes ( J:92084 )

• compared with Fas^lpr homozygotes

decreased susceptibility to systemic lupus erythematosus ( J:92084 )

• mice exhibit reduced serum levels of kappa-chain rheumatoid factor and DNA auto-antibodies, lymphadenopathy, glomerulonephritis, renal immunoglobulin deposits, proteinuria, and end organ disease compared with Fas^lpr homozygotes

decreased autoantibody level ( J:92084 )

• mice exhibit reduced serum levels of kappa-chain rheumatoid factor and DNA auto-antibodies compared to in Ifnar1^tm1Agt homozygotes

decreased anti-nuclear antigen antibody level ( J:92084 )

• DNA auto-antibodies (likely against single stranded DNA) are decreased compared with Fas^lpr homozygotes

glomerulonephritis ( J:92084 )

• in some mice

renal/urinary system

increased urine protein level ( J:92084 )

• in some mice

glomerulonephritis ( J:92084 )

• in some mice

homeostasis/metabolism

increased urine protein level ( J:92084 )

• in some mice

hematopoietic system

decreased IgA level ( J:92084 )

• compared with Fas^lpr homozygotes

decreased IgG2a level ( J:92084 )

• compared with Fas^lpr homozygotes

decreased IgG2b level ( J:92084 )

• compared with Fas^lpr homozygotes

decreased IgG3 level ( J:92084 )

• compared with Fas^lpr homozygotes

increased IgG level ( J:92084 )

• some mice exhibit IgG deposits in the kidney unlike wild-type mice

increased IgG1 level ( J:92084 )

• compared with Fas^lpr homozygotes

decreased IgM level ( J:92084 )

• compared with Fas^lpr homozygotes

Genotype
MGI:4838775

cx69

• Allelic Composition: Fas^lpr/Fas^lpr; Ifnar1^tm1Agt/Ifnar1^tm1Agt; Ifngr1^tm1Agt/Ifngr1^tm1Agt
• Genetic Background: MRL.Cg-Ifngr1^tm1Agt Ifnar1^tm1Agt Fas^lpr

immune system

salivary gland inflammation ( J:92084 )

• mild in some mice

decreased IgG level ( J:92084 )

• modestly compared with Ifngr1^tm1Agt Fas^lpr or Ifnar1^tm1Agt Fas^lpr double homozygotes

increased IgG level ( J:92084 )

• some mice exhibit IgG deposits in the kidney unlike wild-type mice

small lymph nodes ( J:92084 )

• compared with Fas^lpr homozygotes

decreased susceptibility to systemic lupus erythematosus ( J:92084 )

• mice exhibit reduced serum levels of kappa-chain rheumatoid factor and DNA auto-antibodies, lymphadenopathy, glomerulonephritis, renal immunoglobulin deposits, proteinuria, and end organ disease compared with Fas^lpr homozygotes

increased susceptibility to systemic lupus erythematosus ( J:92084 )

• compared with Ifngr1^tm1Agt Fas^lpr double homozygotes

decreased autoantibody level ( J:92084 )

• mice exhibit reduced serum levels of kappa-chain rheumatoid factor and DNA auto-antibodies compared to in Ifngr1^tm1Agt Fas^lpr or Ifnar1^tm1Agt Fas^lpr double homozygotes

decreased anti-nuclear antigen antibody level ( J:92084 )

• compared with Ifngr1^tm1Agt Fas^lpr or Ifnar1^tm1Agt Fas^lpr double homozygotes at 24 weeks

glomerulonephritis ( J:92084 )

• in some mice

renal/urinary system

increased urine protein level ( J:92084 )

• in some mice

glomerulonephritis ( J:92084 )

• in some mice

homeostasis/metabolism

increased urine protein level ( J:92084 )

• in some mice

endocrine/exocrine glands

salivary gland inflammation ( J:92084 )

• mild in some mice

digestive/alimentary system

salivary gland inflammation ( J:92084 )

• mild in some mice

hematopoietic system

decreased IgG level ( J:92084 )

• modestly compared with Ifngr1^tm1Agt Fas^lpr or Ifnar1^tm1Agt Fas^lpr double homozygotes

increased IgG level ( J:92084 )

• some mice exhibit IgG deposits in the kidney unlike wild-type mice

Genotype
MGI:3801419

cx70

• Allelic Composition: Fas^lpr/Fas^lpr; Ifng^tm1Ts/Ifng⁺
• Genetic Background: MRL.Cg-Ifng^tm1Ts Fas^lpr

mortality/aging

premature death ( J:123834 )

• mice become moribund and are sacrificed at 4 months mutants posttransfer of Ifng wild-type F4/80+ macrophages at 2 months while all controls remain alive

immune system

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes

increased autoantibody level ( J:123834 )

• mice develop glomerular autoantibody deposits, but do not develop glomerulonephritis

glomerulonephritis ( J:123834 )

• mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months develop diffuse proliferative glomerulonephritis by 6 months

renal/urinary system

abnormal renal glomerulus morphology ( J:123834 )

• glomeruli are hypercellular in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

• glomerular damage is more severe in mice receiving cell transfer than in control mice not receiving transfers

abnormal glomerular capillary morphology ( J:123834 )

• thickening of capillary walls in glomeruli is observed in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

increased mesangial cell number ( J:123834 )

• mesangial cells are increased in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

glomerulonephritis ( J:123834 )

• mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months develop diffuse proliferative glomerulonephritis by 6 months

homeostasis/metabolism

increased blood urea nitrogen level ( J:123834 )

• BUN levels are elevated at time of death in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

cardiovascular system

abnormal glomerular capillary morphology ( J:123834 )

• thickening of capillary walls in glomeruli is observed in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

cellular

increased mesangial cell number ( J:123834 )

• mesangial cells are increased in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes

hematopoietic system

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes

Genotype
MGI:3801418

cx71

• Allelic Composition: Fas^lpr/Fas^lpr; Ifng^tm1Ts/Ifng^tm1Ts
• Genetic Background: MRL.Cg-Ifng^tm1Ts Fas^lpr

immune system

immune system phenotype ( J:123834 )

N • at 4 months, kidney-infiltrating macrophages are not present; deposits of glomerular immune complexes (ICs) are not observed

N • in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, IC deposition and glomerular proliferation are similar to control mice not receiving transfers

N • in mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months, kidney interstitium remains free of macrophages, T cells, or other lymphocytes (signs of kidney interstitial inflammation) at 2 months post-transfer

N • in mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months, anti-DNA autoantibody production is minimal compared to Ifng-wild-type, Fas^lpr homozygotes; glomerular autoantibody deposits are not observed

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes

• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, migration of macrophages to peritubular and periglomerular areas of kidneys is detected, whereas without transfer, macrophage recruitment to these areas is significantly reduced relative to Fas^lpr homozygotes

kidney inflammation ( J:123834 )

• mice display perivascular infiltrate composed mainly of CD4+ cells

• mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months develop heavy perivascular infiltrates of mainly CD4+ T cells but show no signs of glomerular nephritis, similar to nontransferred controls

• severe multifocal pyogranulomatous nephritis is observed in kidneys of mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months of age, with extensive perivascular and periglomerular accumulation of polymorphonuclear leukocytes and mononuclear cells

lung inflammation ( J:123834 )

• mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months develop diffuse severe acidophilic pneumonia, characterized by intraalveolar accumulation of strongly eosinophilic macrophages with heavy CD3+ cell infiltration; some animals present with peribronchial T cell infiltration

renal/urinary system

kidney inflammation ( J:123834 )

• mice display perivascular infiltrate composed mainly of CD4+ cells

• mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months develop heavy perivascular infiltrates of mainly CD4+ T cells but show no signs of glomerular nephritis, similar to nontransferred controls

• severe multifocal pyogranulomatous nephritis is observed in kidneys of mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages at 2 months of age, with extensive perivascular and periglomerular accumulation of polymorphonuclear leukocytes and mononuclear cells

abnormal renal glomerulus morphology ( J:123834 )

• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, glomerular nephritis is not observed, but severe multifocal pyogranulomatous nephritis in kidneys is observed

respiratory system

lung inflammation ( J:123834 )

• mutants receiving adoptive transfer of Ifng wild-type T cells at 2 months develop diffuse severe acidophilic pneumonia, characterized by intraalveolar accumulation of strongly eosinophilic macrophages with heavy CD3+ cell infiltration; some animals present with peribronchial T cell infiltration

cellular

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes

• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, migration of macrophages to peritubular and periglomerular areas of kidneys is detected, whereas without transfer, macrophage recruitment to these areas is significantly reduced relative to Fas^lpr homozygotes

hematopoietic system

abnormal macrophage chemotaxis ( J:123834 )

• macrophage accumulation is reduced compared to Fas^lpr homozygotes

• in mutants receiving adoptive transfer of Ifng wild-type F4/80+ macrophages, migration of macrophages to peritubular and periglomerular areas of kidneys is detected, whereas without transfer, macrophage recruitment to these areas is significantly reduced relative to Fas^lpr homozygotes

Genotype
MGI:4943704

cx72

• Allelic Composition: Fas^lpr/Fas^lpr; Il27ra^tm1Mak/Il27ra^tm1Mak
• Genetic Background: MRL.Cg-Il27ra^tm1Mak Fas^lpr

mortality/aging

extended life span ( J:122148 )

• 10% of mice die by week 24 compared with 50% of Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

immune system

immune system phenotype ( J:122148 )

N • mice exhibit unaltered lymphocyte compartment compared with Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

increased IgE level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

increased IgG1 level ( J:122148 )

• mice exhibit increased IgG1 depositions in the kidneys compared with Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

• IgG1 serum levels are increased compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

decreased IgG2a level ( J:122148 )

• mice exhibit reduced IgG2a renal deposits and serum levels compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

abnormal T-helper 2 physiology ( J:122148 )

• Th2-type immune response is favored compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

increased circulating interleukin-4 level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

increased circulating interleukin-5 level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

decreased interferon-gamma secretion ( J:122148 )

• 10-fold in stimulated CD4+ T cells compared with similarly treated Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ cells

decreased susceptibility to systemic lupus erythematosus ( J:122148 )

• mice exhibit improved survival, creatinine serum level, blood urea nitrogen serum level, and renal injury compared with Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

decreased anti-double stranded DNA antibody level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

glomerulonephritis ( J:122148 )

• mice develop membranous glomerulonephritis

renal/urinary system

glomerulonephritis ( J:122148 )

• mice develop membranous glomerulonephritis

homeostasis/metabolism

decreased circulating creatinine level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

decreased blood urea nitrogen level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

increased circulating interleukin-4 level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

increased circulating interleukin-5 level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

hematopoietic system

increased IgE level ( J:122148 )

• compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

increased IgG1 level ( J:122148 )

• mice exhibit increased IgG1 depositions in the kidneys compared with Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

• IgG1 serum levels are increased compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

decreased IgG2a level ( J:122148 )

• mice exhibit reduced IgG2a renal deposits and serum levels compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

abnormal T-helper 2 physiology ( J:122148 )

• Th2-type immune response is favored compared to in Fas^lpr/Fas^lpr Il27ra^tm1Mak/Il27ra⁺ mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
membranous glomerulonephritis		DOID:10976		J:122148

Genotype
MGI:3799736

cx73

• Allelic Composition: Fas^lpr/Fas^lpr; Il4^tm1Cgn/Il4^tm1Cgn
• Genetic Background: MRL.Cg-Il4^tm1Cgn Fas^lpr

immune system

lacrimal gland inflammation ( J:132514 )

• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells

• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 16% of infiltrate

• B cells are somewhat less abundant in infiltrates (18%) than in double mutants

glomerulonephritis ( J:132514 )

• less severe than MRL/MpJ-Fas^lpr mice at 3 and 5 months

renal/urinary system

glomerulonephritis ( J:132514 )

• less severe than MRL/MpJ-Fas^lpr mice at 3 and 5 months

vision/eye

lacrimal gland inflammation ( J:132514 )

• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells

• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 16% of infiltrate

• B cells are somewhat less abundant in infiltrates (18%) than in double mutants

endocrine/exocrine glands

lacrimal gland inflammation ( J:132514 )

• dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells

• predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 16% of infiltrate

• B cells are somewhat less abundant in infiltrates (18%) than in double mutants

Genotype
MGI:3769143

cx74

• Allelic Composition: Fas^lpr/Fas^lpr; Irf1^tm1Mak/Irf1^tm1Mak
• Genetic Background: MRL.Cg-Irf1^tm1Mak Fas^lpr

mortality/aging

premature death ( J:114771 )

• 50% of mice die by 45 weeks; survival is increased relative to MRL-Fas^lpr mice

immune system

immune system phenotype ( J:114771 )

N • TNF alpha production is not significantly different from Fas^lpr, Irf1-sufficient mice

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• at 12 weeks, splenic CD4+CD25+ T cells are increased in percentage compared to wild-type MRL-Fas^lpr mice; percentage increases from 27.1% at 8 weeks to 40.3% at 26 weeks in wild-type mice, double mutants have 60.6% at 26 weeks

• 26 week old mice have a percentage of CD4+CD25+CD62L+ T cells (32.2%) compared to wild-type MRL-Fas^lpr mice (13.1%)

abnormal cytokine secretion ( J:114771 )

• mesangial cells from 8- and 26-week old mice show significantly less Il12 production than Fas^lpr, Irf1-sufficient cells upon stimulation with LPS and interferon gamma

decreased anti-double stranded DNA antibody level ( J:114771 )

• levels of anti-dsDNA IgG2a are significantly decreased relative to Fas^lpr, Irf1-sufficient mice

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• at 12 weeks, splenic CD4+CD25+ T cells are increased in percentage compared to wild-type MRL-Fas^lpr mice; percentage increases from 27.1% at 8 weeks to 40.3% at 26 weeks in wild-type mice, double mutants have 60.6% at 26 weeks

• 26 week old mice have a percentage of CD4+CD25+CD62L+ T cells (32.2%) compared to wild-type MRL-Fas^lpr mice (13.1%)

renal/urinary system

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:114771 )

N • only 1 mouse had abnormal urine protein levels (above 200 mg/dl) at 24 weeks of age

cellular

abnormal cell physiology ( J:114771 )

• in response to LPS + IFN gamma stimulation, mesangial cells show significantly lower activation than cells from MRL-Fas^lpr mice

integument

integument phenotype ( J:114771 )

N • mice do not show characteristic signs of skin disease; at 26 weeks of age, 7/10 mice show no skin involvement, while 3 show minimal skin irritation, compared to 8/10 Fas^lpr, Irf1 sufficient mice displaying moderate to severe skin involvement

Genotype
MGI:3769144

cx75

• Allelic Composition: Fas^lpr/Fas^lpr; Irf1^tm1Mak/Irf1⁺
• Genetic Background: MRL.Cg-Irf1^tm1Mak Fas^lpr

mortality/aging

premature death ( J:114771 )

• 50% of mice die by 52 weeks; survival is increased relative to MRL-Fas^lpr mice

renal/urinary system

increased urine protein level ( J:114771 )

• not significantly different from Fas^lpr, Irf1-null mice or Fas^lpr, Irf1-sufficient mice

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• mice display similar T cell population profiles to Fas^lpr, Irf1-null mice

immune system

immune system phenotype ( J:114771 )

N • TNF alpha production is not significantly different Fas^lpr, Irf1-sufficient mice or Fas^lpr, Irf1-null mice

increased CD4-positive, alpha-beta T cell number ( J:114771 )

• mice display similar T cell population profiles to Fas^lpr, Irf1-null mice

increased anti-double stranded DNA antibody level ( J:114771 )

• at 26 weeks of age, levels are significantly higher relative to Fas^lpr, Irf1-null mice

glomerulonephritis ( J:114771 )

• at 26 weeks of age, mice show much less severe renal disease including IgG and C3 glomerular deposition compared to Fas^lpr homozygotes

homeostasis/metabolism

increased urine protein level ( J:114771 )

• not significantly different from Fas^lpr, Irf1-null mice or Fas^lpr, Irf1-sufficient mice

integument

abnormal skin condition ( J:114771 )

• mice display varying severity of skin irritation ranging from little or none to mild or moderate to severe

Genotype
MGI:3800806

cx76

• Allelic Composition: Fas^lpr/Fas^lpr; Selplg^tm1Fur/Selplg^tm1Fur
• Genetic Background: MRL.Cg-Selplg^tm1Fur Fas^lpr

mortality/aging

premature death ( J:127199 )

• overall survival is reduced compared to Fas^lpr homozygotes (median survival is 21 weeks vs 26 weeks for Fas mutants); renal lesions are severe at time of death

immune system

abnormal chemokine level ( J:127199 )

• significant increases are observed at 16 weeks, in contrast to Selp-null, Fas double mutants; levels are significantly higher than control at 20 weeks

glomerulonephritis ( J:127199 )

• at 20 weeks of age, kidneys display higher lesion scores than controls

dermatitis ( J:127199 )

• double mutants show more rapid onset of cutaneous inflammation than Fas^lpr homozygotes

renal/urinary system

glomerulonephritis ( J:127199 )

• at 20 weeks of age, kidneys display higher lesion scores than controls

homeostasis/metabolism

abnormal chemokine level ( J:127199 )

• significant increases are observed at 16 weeks, in contrast to Selp-null, Fas double mutants; levels are significantly higher than control at 20 weeks

integument

dermatitis ( J:127199 )

• double mutants show more rapid onset of cutaneous inflammation than Fas^lpr homozygotes

Genotype
MGI:3799723

cx77

• Allelic Composition: Fas^lpr/Fas^lpr; Selp^tm1Bay/Selp^tm1Bay
• Genetic Background: MRL.Cg-Selp^tm1Bay Fas^lpr

mortality/aging

premature death ( J:127199 )

• overall survival is reduced compared to Fas^lpr homozygotes (median survival is 20 weeks vs 26 weeks for Fas mutants); renal lesions are severe at time of death

immune system

abnormal leukocyte adhesion ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

impaired leukocyte tethering or rolling ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

increased neutrophil cell number ( J:127199 )

• severe neutrophil accumulation at 20 weeks is observed in kidneys

abnormal chemokine secretion ( J:127199 )

• in kidney and cultured primary renal endothelial cells, levels of CCL2 are elevated compared to Fas^lpr controls at 20 weeks; expression levels are increased further upon LPS treatment of cells

glomerulonephritis ( J:127199 )

• at 20 weeks of age, kidneys display higher lesion scores than controls

dermatitis ( J:127199 )

• double mutants show more rapid onset of cutaneous inflammation than Fas^lpr homozygotes

hematopoietic system

abnormal leukocyte adhesion ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

impaired leukocyte tethering or rolling ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

increased neutrophil cell number ( J:127199 )

• severe neutrophil accumulation at 20 weeks is observed in kidneys

renal/urinary system

renal necrosis ( J:127199 )

• at 20 weeks of age, severely affected glomeruli display necrosis of large areas of the tuft

abnormal renal glomerular capsule morphology ( J:127199 )

• at 20 weeks of age, severely affected glomeruli display capsular fibrosis and proliferation of the lining of Bowman's capsule

fused podocyte foot processes ( J:127199 )

• at 20 weeks of age, foot processes are fused

podocyte foot process effacement ( J:127199 )

• at 20 weeks of age, foot processes are diffusely effaced

abnormal renal glomerulus morphology ( J:127199 )

• lesions at 20 weeks are characterized by neutrophil infiltration of the glomerular tuft, proliferation of mesangial and endothelial cells, mild multifocal tubular atrophy, and interstitial mixed inflammatory cell accumulation

• more severely affected glomeruli have necrosis of large areas of the tuft, fibrin deposition, proliferation of lining of Bowman's capsule with fusion of the tuft (synechia), capsular fibrosis, and pericapsular lymphocyte accumulation

• subepithelial and subendothelial electron-dense deposits are detected

abnormal glomerular capillary endothelium morphology ( J:127199 )

• at 20 weeks of age, proliferation of endothelial cells is observed

increased mesangial cell number ( J:127199 )

• at 20 weeks of age, cellularity of mesangium is moderately increased

glomerulonephritis ( J:127199 )

• at 20 weeks of age, kidneys display higher lesion scores than controls

expanded mesangial matrix ( J:127199 )

• at 20 weeks of age, markedly expanded mesangium due to mesangial matrix increase is observed

glomerular crescent ( J:127199 )

• at 20 weeks of age, proliferation of lining of Bowman's capsule is observed

renal glomerular synechia ( J:127199 )

• at 20 weeks of age, proliferation of lining of Bowman's capsule with fusion of the tuft (synechia) is observed

renal glomerulus fibrosis ( J:127199 )

• at 20 weeks of age, severely affected glomeruli exhibit fibrin deposition

renal tubule atrophy ( J:127199 )

• at 20 weeks of age, mild multifocal tubular atrophy is observed

kidney failure ( J:127199 )

• progressive decline in renal function is observed, during progression to end-stage renal disease

cardiovascular system

abnormal glomerular capillary endothelium morphology ( J:127199 )

• at 20 weeks of age, proliferation of endothelial cells is observed

vascular inflammation ( J:127199 )

integument

dermatitis ( J:127199 )

• double mutants show more rapid onset of cutaneous inflammation than Fas^lpr homozygotes

cellular

increased mesangial cell number ( J:127199 )

• at 20 weeks of age, cellularity of mesangium is moderately increased

renal necrosis ( J:127199 )

• at 20 weeks of age, severely affected glomeruli display necrosis of large areas of the tuft

abnormal leukocyte adhesion ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

impaired leukocyte tethering or rolling ( J:126009 )

• rolling is dramatically reduced, but not eliminated, in mutants compared to controls

• in mice chronically treated with anti-E-selectin antibodies, rolling is completely eliminated

Genotype
MGI:4944218

cx78

• Allelic Composition: Fas^lpr/Fas^lpr; Tcra^tm1Mjo/Tcra⁺
• Genetic Background: MRL.Cg-Tcra^tm1Mjo Fas^lpr

immune system

immune system phenotype ( J:108590 )

N • no difference in the susceptibility to systemic lupus erythematosus is detected compared to wild-type controls

Genotype
MGI:5478500

cx79

• Allelic Composition: Fas^lpr/Fas^lpr; Tlr9^tm1Aki/Tlr9^tm1Aki
• Genetic Background: MRL.Cg-Tlr9^tm1Aki Fas^lpr

mortality/aging

premature death ( J:113557 )

• mutants show accelerated mortality relative to Fas^lpr homozygotes, with a median survival of 16.4 weeks compared to 25.1 weeks for Fas^lpr homozygotes

immune system

enlarged spleen ( J:113557 )

• splenomegaly is increased more than in Fas^lpr homozygotes

increased double-negative T cell number ( J:113557 )

• 3-fold increase in the number of CD4- CD8- double-negative T cells in the spleen compared to Fas^lpr homozygotes

increased CD4-positive, alpha-beta T cell number ( J:113557 )

• increase in number of CD4+ helper T cells compared to Fas^lpr homozygotes

abnormal B cell activation ( J:113557 )

• B cells have increased expression of activation markers CD44 and CD69 compared to Fas^lpr homozygotes, indicating increased B cell activation

increased IgG level ( J:113557 )

• increase in concentration of every IgG isotype compared to Fas^lpr homozygotes, with most prominent increases in IgG2a and IgG3

increased IgG2a level ( J:113557 )

• compared to Fas^lpr homozygotes

increased IgG3 level ( J:113557 )

• compared to Fas^lpr homozygotes

increased circulating interferon-alpha level ( J:113557 )

• mice exhibit increased serum IFN-alpha concentration compared to Fas^lpr homozygotes

enlarged lymph nodes ( J:113557 )

• lymphadenopathy is increased more than in Fas^lpr homozygotes

abnormal plasmacytoid dendritic cell physiology ( J:113557 )

• splenic plasmacytoid dendritic cells (pDC) are more activated than those in single Fas^lpr homozygotes based on increased expression of MHC class II

• plasmacytoid DCs have an increased expression of the activation markers CD80 and CD86 compared to Fas^lpr homozygotes

increased susceptibility to systemic lupus erythematosus ( J:113557 )

• mutants exhibit an increase in the incidence and severity of autoimmune skin disease compared to single Fas^lpr homozygous littermates

• mutants develop exacerbated kidney disease (lupus nephritis) compared to single Fas^lpr homozygotes

decreased autoantibody level ( J:113557 )

• mutants show impaired ability to generate antibodies to DNA antigens compared to single Fas^lpr homozygotes, however they do generate antibodies reacting with cytoplasmic antigens that may include RNA

increased autoantibody level ( J:113557 )

• mice exhibit an elevated baseline level of anti-Smith-ribonucleoprotein autoantibodies compared to single Fas^lpr homozygotes

kidney inflammation ( J:113557 )

• mutants develop exacerbated kidney disease (lupus nephritis) compared to Fas^lpr homozygotes

• a trend towards increased severity of interstitial infiltrates compared to Fas^lpr homozygotes

glomerulonephritis ( J:113557 )

• increase in glomerular size, cellularity, and protein deposition in kidneys leading to glomerulonephritis

renal/urinary system

kidney inflammation ( J:113557 )

• mutants develop exacerbated kidney disease (lupus nephritis) compared to Fas^lpr homozygotes

• a trend towards increased severity of interstitial infiltrates compared to Fas^lpr homozygotes

glomerulonephritis ( J:113557 )

• increase in glomerular size, cellularity, and protein deposition in kidneys leading to glomerulonephritis

abnormal renal glomerulus morphology ( J:113557 )

• glomerular size and cellularity are increased compared to Fas^lpr homozygotes

hematopoietic system

enlarged spleen ( J:113557 )

• splenomegaly is increased more than in Fas^lpr homozygotes

increased double-negative T cell number ( J:113557 )

• 3-fold increase in the number of CD4- CD8- double-negative T cells in the spleen compared to Fas^lpr homozygotes

increased CD4-positive, alpha-beta T cell number ( J:113557 )

• increase in number of CD4+ helper T cells compared to Fas^lpr homozygotes

abnormal B cell activation ( J:113557 )

• B cells have increased expression of activation markers CD44 and CD69 compared to Fas^lpr homozygotes, indicating increased B cell activation

increased IgG level ( J:113557 )

• increase in concentration of every IgG isotype compared to Fas^lpr homozygotes, with most prominent increases in IgG2a and IgG3

increased IgG2a level ( J:113557 )

• compared to Fas^lpr homozygotes

increased IgG3 level ( J:113557 )

• compared to Fas^lpr homozygotes

homeostasis/metabolism

increased circulating interferon-alpha level ( J:113557 )

• mice exhibit increased serum IFN-alpha concentration compared to Fas^lpr homozygotes

growth/size/body

enlarged spleen ( J:113557 )

• splenomegaly is increased more than in Fas^lpr homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:113557

Genotype
MGI:3800181

cx80

• Allelic Composition: Fas^lpr/Fas^lpr; Tnfrsf13c^Bcmd1/Tnfrsf13c⁺
• Genetic Background: MRL.Cg-Tnfrsf13c^Bcmd1 Fas^lpr

hematopoietic system

decreased B cell number ( J:122315 )

• numbers are reduced

decreased marginal zone B cell number ( J:122315 )

immune system

decreased B cell number ( J:122315 )

• numbers are reduced

decreased marginal zone B cell number ( J:122315 )

Genotype
MGI:3800222

cx81

• Allelic Composition: Fas^lpr/Fas^lpr; Tnfrsf9^tm1Byk/Tnfrsf9^tm1Byk
• Genetic Background: MRL.Cg-Tnfrsf9^tm1Byk Fas^lpr

cellular

increased lacrimal gland apoptosis ( J:126929 )

• more apoptotic cells are detected relative to wild-type Tnfrsf9, Fas ^lpr controls

mortality/aging

premature death ( J:127197 )

• by 5 months, 80% mortality is observed compared to 40% in Tnfrsf9-sufficient, Fas-null mice; by 4 months, mice become increasingly moribund and display reduced activity

hematopoietic system

hematopoietic system phenotype ( J:127197 )

N • CD8beta+ T cells are not altered in number at any age

enlarged spleen ( J:127197 )

• significant enlargement of axillary lymph nodes is seen at 5 months compared to Tnfrsf9-wt, Fas-null mice

increased double-negative T cell number ( J:126929 , J:127197 )

• in lacrimal glands, DN T cell percentages are about 2-fold greater than in wild-type Tnfrsf9, Fas ^lpr controls; similar increases are seen in spleen and salivary glands (J:126929)

• increased proportion seen in spleen compared to Tnfrsf9-sufficient, Fas-null mice (J:127197)

increased B-1 B cell number ( J:127197 )

• percentages of B-1 (B220+ CD5+) cells are increased significantly in peritoneums and slightly higher in spleens

increased B-2 B cell number ( J:127197 )

• percentages of B-2( B220+ CD5-) cells are increased significantly in peritoneums and slightly higher in spleens

increased CD4-positive, alpha-beta T cell number ( J:126929 , J:127197 )

• 3- and 5-month old mice show elevated CD4+ T cell numbers in lacrimal glands (J:126929)

• mice display early increases in CD4+ T cells in spleen, and numbers keep rising (J:127197)

increased spleen germinal center number ( J:127197 )

• greatly increased germinal center formation is observed compared to Tnfrsf9-sufficient, Fas-null mice

increased immunoglobulin level ( J:127197 )

• circulating titres are elevated compared with compared to Tnfrsf9-sufficient, Fas-null mice

immune system

lacrimal gland inflammation ( J:126929 )

• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas ^lpr homozygotes

• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age

enlarged spleen ( J:127197 )

• significant enlargement of axillary lymph nodes is seen at 5 months compared to Tnfrsf9-wt, Fas-null mice

increased double-negative T cell number ( J:126929 , J:127197 )

• in lacrimal glands, DN T cell percentages are about 2-fold greater than in wild-type Tnfrsf9, Fas ^lpr controls; similar increases are seen in spleen and salivary glands (J:126929)

• increased proportion seen in spleen compared to Tnfrsf9-sufficient, Fas-null mice (J:127197)

increased B-1 B cell number ( J:127197 )

• percentages of B-1 (B220+ CD5+) cells are increased significantly in peritoneums and slightly higher in spleens

increased B-2 B cell number ( J:127197 )

• percentages of B-2( B220+ CD5-) cells are increased significantly in peritoneums and slightly higher in spleens

increased CD4-positive, alpha-beta T cell number ( J:126929 , J:127197 )

• 3- and 5-month old mice show elevated CD4+ T cell numbers in lacrimal glands (J:126929)

• mice display early increases in CD4+ T cells in spleen, and numbers keep rising (J:127197)

increased spleen germinal center number ( J:127197 )

• greatly increased germinal center formation is observed compared to Tnfrsf9-sufficient, Fas-null mice

increased immunoglobulin level ( J:127197 )

• circulating titres are elevated compared with compared to Tnfrsf9-sufficient, Fas-null mice

enlarged lymph nodes ( J:127197 )

• significant enlargement at 5 months compared to Tnfrsf9-wt, Fas-null mice

increased interleukin-4 secretion ( J:126929 )

• in lacrimal glands, increased levels of Il-4 are detected compared to controls

increased susceptibility to systemic lupus erythematosus ( J:127197 )

• phenotypic manifestations are increased relative to Fas^lpr homozygotes

increased anti-nuclear antigen antibody level ( J:127197 )

• serum titres of anti-nuclear IgG1/2a are increased at 3 and 5 months

• anti-DNA antibody production is increased compared to Tnfrsf9-sufficient, Fas-null mice

renal/urinary system

abnormal kidney morphology ( J:126929 )

• increased immunoglobulin deposits are detected in kidneys compared to controls

cortical renal glomerulopathies ( J:127197 )

• mice show exacerbated renal injury, with increased glomerular infiltrates

renal glomerular protein deposits ( J:127197 )

• IgG and C3 depositions in kidneys are increased compared with Tnfrsf9-sufficient, Fas-null mice

craniofacial

abnormal outer ear morphology ( J:127197 )

• from 4 months of age, >60% of mice display progressive erosion of pinnae

hearing/vestibular/ear

abnormal outer ear morphology ( J:127197 )

• from 4 months of age, >60% of mice display progressive erosion of pinnae

endocrine/exocrine glands

increased lacrimal gland apoptosis ( J:126929 )

• more apoptotic cells are detected relative to wild-type Tnfrsf9, Fas ^lpr controls

abnormal lacrimal gland morphology ( J:126929 )

• increased deposits of IgG1, but not IgG2a are detected in lacrimal glands at 3 and 5 months

lacrimal gland inflammation ( J:126929 )

• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas ^lpr homozygotes

• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age

vision/eye

increased lacrimal gland apoptosis ( J:126929 )

• more apoptotic cells are detected relative to wild-type Tnfrsf9, Fas ^lpr controls

abnormal lacrimal gland morphology ( J:126929 )

• increased deposits of IgG1, but not IgG2a are detected in lacrimal glands at 3 and 5 months

lacrimal gland inflammation ( J:126929 )

• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas ^lpr homozygotes

• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age

integument

skin lesions ( J:127197 )

• by 5 months, skin lesions around tip of nose and around ears are more pronounced than in Tnfrsf9-wt, Fas-null mice

growth/size/body

abnormal outer ear morphology ( J:127197 )

• from 4 months of age, >60% of mice display progressive erosion of pinnae

enlarged spleen ( J:127197 )

• significant enlargement of axillary lymph nodes is seen at 5 months compared to Tnfrsf9-wt, Fas-null mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:120559
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:120559

Genotype
MGI:3613073

cx82

• Allelic Composition: Agtpbp1^atms/Agtpbp1^atms; Fas^lpr/Fas^lpr
• Genetic Background: MRL/Mp-Agtpbp1^atms Fas^lpr

behavior/neurological

ataxia ( J:103944 )

immune system

enlarged spleen ( J:103944 )

• spleen is enlarged but to a smaller extent than in single homozygous Fas^lpr mice

enlarged lymph nodes ( J:103944 )

• mild lymphadenopathy that occurs late and slowly compared to homozygous Fas^lpr mice

hematopoietic system

enlarged spleen ( J:103944 )

• spleen is enlarged but to a smaller extent than in single homozygous Fas^lpr mice

integument

integument phenotype ( J:103944 )

N • have a normal smooth fur appearance unlike single homozygous Fas^lpr mice

growth/size/body

enlarged spleen ( J:103944 )

• spleen is enlarged but to a smaller extent than in single homozygous Fas^lpr mice

Genotype
MGI:3613075

cx83

• Allelic Composition: Agtpbp1^atms/Agtpbp1^atms; Fas^lpr/?
• Genetic Background: MRL/Mp-Agtpbp1^atms Fas^lpr

behavior/neurological

ataxia ( J:103945 )

• subtle but abnormal motion of the body swaying laterally is seen at about 21 days of age

• persistent mild to moderate ataxia is noticeable throughout life, however it does not worsen with age

• width of steps is narrower, but do not see widening of the distance between both feet

impaired coordination ( J:103945 )

• cannot stay on the rotarod at all and fall down within the first 2-3 seconds

nervous system

abnormal stellate ganglion morphology ( J:103945 )

• greater density of stellate neurons along with reactive glia

decreased brain weight ( J:103945 )

• low in 4.5 month old mice (389 mg vs. 503 mg in controls)

abnormal cerebellum morphology ( J:103945 )

abnormal cerebellar foliation ( J:103945 )

• incomplete foliation, particularly in the central lobules

decreased Purkinje cell number ( J:103945 )

• 50% loss of Purkinje cells at 3 weeks of age, with cell loss rapidly accelerating so that by 6 weeks of age, almost all are lost, however do not see any severe loss of neural cells in the cerebellum and brainstem

thin cerebellar granule layer ( J:103945 )

• thinning of the granular layer seems to be due to a decrease in the number of granule cells per unit area

thin cerebellar molecular layer ( J:103945 )

• thinner at 4.5 months of age but not at 3 weeks of age, due to loss of Purkinje dendritic trees

small cerebellum ( J:103945 )

• small in 4.5 month old mice

reproductive system

oligozoospermia ( J:103945 )

♂ • mature sperm are seldom seen in the testis, however primary spermatocytes and spermatogonia are observed in the seminiferous tubules

arrest of spermatogenesis ( J:103945 )

♂ • cessation of differentiation mainly at the spermatid stage and degeneration of cells

female infertility ( J:103945 )

♀ • although females are infertile, no pathological change in the ovaries is observed and ova can be fertilized in vitro

male infertility ( J:103945 )

♂

cellular

oligozoospermia ( J:103945 )

♂ • mature sperm are seldom seen in the testis, however primary spermatocytes and spermatogonia are observed in the seminiferous tubules

Genotype
MGI:3761613

cx84

• Allelic Composition: Fas^lpr/Fas^lpr; Sh2d1a^rpl/Sh2d1a^rpl
• Genetic Background: MRL/Mp-Fas^lpr Sh2d1a^rpl

immune system

abnormal immune system physiology ( J:126261 )

♀ • the hypergammaglobulinemia and autoantibody production normally associated with MRL mice are mostly absent in this strain

increased anti-nuclear antigen antibody level ( J:126261 )

♀ • levels are slightly elevated compared to wild-type mice

Genotype
MGI:3663021

cx85

• Allelic Composition: Fas^lpr/Fas^lpr; Tg(Ins2-Fasl)24Ach/0
• Genetic Background: NOD.Cg-Fas^lpr Tg(Ins2-Fasl)24Ach

immune system

decreased susceptibility to autoimmune diabetes ( J:81416 )

• when mice are injected with islet-specific CD8+ T cells, 0/5 transgenic Fas-deficient mice become diabetic whereas 5/5 transgenic Fas-sufficient mice develop diabetes 5 days after transfer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:81416

Genotype
MGI:3622770

cx86

• Allelic Composition: Fas^lpr/Fas^lpr; Tg(INS-Il10)#Sar/0
• Genetic Background: NOD.Cg-Fas^lpr Tg(INS-Il10)#Sar

immune system

insulitis ( J:64051 )

• islets of transgenic mice show extensive leukocytic infiltration compared to Fas-sufficient transgenic mice

increased susceptibility to autoimmune diabetes ( J:64051 )

• mice of the N3-4 and N8-9 NOD backcross develop accelerated diabetes with most developing diabetes by 10 weeks of age while lpr-deficient NOD mice are free from spontaneous insulitis and diabetes

• mice are considered diabetic after a blood glucose measure of >300 mg/dl

endocrine/exocrine glands

insulitis ( J:64051 )

• islets of transgenic mice show extensive leukocytic infiltration compared to Fas-sufficient transgenic mice