All Phenotypes Tg(IghelMD4)4Ccg MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Tg(IghelMD4)4Ccg
transgene insertion 4, Christopher C Goodnow
MGI:2384162

Summary

40 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cd19^tm1(cre)Cgn/Cd19⁺ Pten^tm1Hwu/Pten^tm1Hwu Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:5007685
cn2	Dicer1^tm1Mmk/Dicer1^tm1Mmk Tg(IghelMD4)4Ccg/0 Cd79a^tm1(cre)Reth/Cd79a⁺	involves: BALB/c	MGI:3797394
cn3	Cd79a^tm1(cre)Reth/Cd79a⁺ Phf5a^tm1.1Oux/Phf5a^tm1.1Oux Tg(IghelMD4)4Ccg/0	involves: BALB/c * C57BL/6 * C57BL/6J	MGI:7611733
cx4	Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0	C57BL/6-Tg(IghelMD4)4Ccg Tg(KLK4mHEL)6Ccg	MGI:3793443
cx5	Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	C57BL/6-Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg	MGI:3793461
cx6	Tlr4^Lps-d/Tlr4^Lps-d Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0	involves: 129P2/OlaHsd * C3H/HeJ * C57BL/6	MGI:3694809
cx7	Lyn^tm1Ard/Lyn⁺ Ptpn6^me-v/Ptpn6⁺ Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3852087
cx8	Tlr9^tm1Aki/Tlr9^tm1Aki Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3694807
cx9	Myd88^tm1Aki/Myd88^tm1Aki Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3694808
cx10	Prkcd^tm1Qxu/Prkcd^tm1Qxu Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3841844
cx11	Prkcd^tm1Qxu/Prkcd^tm1Qxu Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3841845
cx12	Lyn^tm1Ard/Lyn^tm1Ard Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3852084
cx13	Lyn^tm1Ard/Lyn⁺ Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3852085
cx14	Ptpn6^me-v/Ptpn6⁺ Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3852086
cx15	Cd22^tm1Eac/Cd22⁺ Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3852088
cx16	Cd22^tm1Eac/Cd22⁺ Lyn^tm1Ard/Lyn⁺ Ptpn6^me-v/Ptpn6⁺ Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3852089
cx17	Cd22^tm1Eac/Cd22⁺ Ptpn6^me-v/Ptpn6⁺ Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3852090
cx18	Cd22^tm1Eac/Cd22⁺ Lyn^tm1Ard/Lyn⁺ Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:3852091
cx19	Cd19^tm1(cre)Cgn/Cd19^tm1(cre)Cgn Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:5007683
cx20	Cd19^tm1(cre)Cgn/Cd19^tm1(cre)Cgn Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:5007684
cx21	Card19^tm1Rwen/Card19^tm1Rwen Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6	MGI:7514984
cx22	Card19^tm1Rwen/Card19^tm1Rwen Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JSfd	MGI:7514963
cx23	Fnip1^{Gt(RRM154)Byg}/Fnip1^{Gt(RRM154)Byg} Tg(IghelMD4)4Ccg/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL	MGI:5445166
cx24	Cd79b^tm1Mnz/Cd79b^tm1Mnz Tg(IghelMD4)4Ccg/0 Tg(Rag2-Igb)1Mnz/0	involves: 129S1/Sv * C57BL/6	MGI:4453800
cx25	Cd79b^tm1Mnz/Cd79b^tm1Mnz Tg(BCL2)22Wehi/0 Tg(IghelMD4)4Ccg/0 Tg(Rag2-Igb)1Mnz/0	involves: 129S1/Sv * C57BL/6 * C57BL/6JWehi * SJL/JWehi	MGI:4453802
cx26	Endou^tm1Tft/Endou^tm1Tft Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	involves: 129S/SvEv * C57BL/6 * C57BL/6JSfd	MGI:5582909
cx27	Cr2^{tm2.1(HLA-A)Crr}/Cr2^{tm2.1(HLA-A)Crr} Tg(IghelMD4)4Ccg/?	involves: C57BL/6	MGI:4356056
cx28	Tg(IghelMD4)4Ccg/? Tg(KLK4mHEL)6Ccg/?	involves: C57BL/6	MGI:3799746
cx29	Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	involves: C57BL/6	MGI:3799370
cx30	Atp11c^ambr/Y Tg(IghelMD4)4Ccg/0	involves: C57BL/6 * C57BL/6JApb	MGI:5006965
cx31	Fnip1^tm1.2Baba/Fnip1^tm1.2Baba Tg(IghelMD4)4Ccg/0	involves: C57BL/6 * C57BL/6J * FVB/N * SJL	MGI:5445165
cx32	Bcl6^tm1.1Toka/Bcl6^tm1.1Toka Tg(IghelMD4)4Ccg/0	involves: C57BL/6 * NZB	MGI:5140809
cx33	Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0	NOD.B6-Tg(IghelMD4)4Ccg Tg(KLK4mHEL)6Ccg/Dvs	MGI:3793442
cx34	Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0	NOD.B6-Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg/Dvs	MGI:3793444
cx35	Ighm^tm1Cgn/Ighm^tm1Cgn Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg	NOD.Cg-Ighm^tm1Cgn Tg(IghelMD4)4Ccg/DvsJ	MGI:3793299
tg36	Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg	involves: C57BL/6	MGI:5006966
tg37	Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg	NOD.B6-Tg(IghelMD4)4Ccg/DvsJ	MGI:3793301
tg38	Tg(IghelMD4)4Ccg/0	C57BL/6-Tg(IghelMD4)4Ccg	MGI:3793440
tg39	Tg(IghelMD4)4Ccg/0	involves: C3H/HeJ * C57BL/6	MGI:3694805
tg40	Tg(IghelMD4)4Ccg/0	involves: C57BL/6	MGI:3694806

Allelic Composition	Cd19^tm1(cre)Cgn/Cd19⁺ Pten^tm1Hwu/Pten^tm1Hwu Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0
Genetic Background	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd19^tm1(cre)Cgn mutation (11 available); any Cd19 mutation (60 available)
Pten^tm1Hwu mutation (16 available); any Pten mutation (88 available)
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(ML5sHEL)5Ccg mutation (2 available)

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

immune system

abnormal peripheral B cell anergy ( J:155314 )

• failed tolerance induction resulting in abundant autoantibody production, indicating that B cells are prevented from acquiring an anergic state

• B cells have about 10 fold lower bound HEL than in mutants with intact Pten, suggesting that receptor occupancy is reduced on mutant autoreactive B cells and that less HEL is available in adults for inducing and sustaining anergy

• increasing the concentration of free self-antigen confers an anergic phenotype on mutant B cells, but they remain long-lived

Allelic Composition	Dicer1^tm1Mmk/Dicer1^tm1Mmk Tg(IghelMD4)4Ccg/0 Cd79a^tm1(cre)Reth/Cd79a⁺
Genetic Background	involves: BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd79a^tm1(cre)Reth mutation (3 available); any Cd79a mutation (24 available)
Dicer1^tm1Mmk mutation (0 available); any Dicer1 mutation (96 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

decreased B cell number ( J:135783 )

• while B cell numbers are increased relative to in Cd79a^tm1(cre)Reth/Cd79a⁺ Dicer1^tm1Mmk/Dicer1^tm1Mmk mice, numbers are still lower than in wild-type mice

decreased mature B cell number ( J:135783 )

hematopoietic system

decreased B cell number ( J:135783 )

• while B cell numbers are increased relative to in Cd79a^tm1(cre)Reth/Cd79a⁺ Dicer1^tm1Mmk/Dicer1^tm1Mmk mice, numbers are still lower than in wild-type mice

decreased mature B cell number ( J:135783 )

Allelic Composition	Cd79a^tm1(cre)Reth/Cd79a⁺ Phf5a^tm1.1Oux/Phf5a^tm1.1Oux Tg(IghelMD4)4Ccg/0
Genetic Background	involves: BALB/c * C57BL/6 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd79a^tm1(cre)Reth mutation (3 available); any Cd79a mutation (24 available)
Phf5a^tm1.1Oux mutation (0 available); any Phf5a mutation (19 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

hematopoietic system

abnormal B cell number ( J:345807 )

• addition of a pre-rearranged IgH transgene partially but significantly increases the number of CD19+ B cells

immune system

abnormal B cell number ( J:345807 )

• addition of a pre-rearranged IgH transgene partially but significantly increases the number of CD19+ B cells

Allelic Composition	Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0
Genetic Background	C57BL/6-Tg(IghelMD4)4Ccg Tg(KLK4mHEL)6Ccg

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(KLK4mHEL)6Ccg mutation (2 available)

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

immune system

decreased B cell number ( J:89156 )

• the number of B cells found in the spleen is decreased by more than 6-fold compared to mice carrying just the antibody transgene

• very few of the remaining B cells expresses the transgenic antibody

• the number of B cells expressing the transgenic antibody is 5.9% of that found in singly transgenic NOD mice carrying only the antibody transgene

hematopoietic system

decreased B cell number ( J:89156 )

• the number of B cells found in the spleen is decreased by more than 6-fold compared to mice carrying just the antibody transgene

• very few of the remaining B cells expresses the transgenic antibody

• the number of B cells expressing the transgenic antibody is 5.9% of that found in singly transgenic NOD mice carrying only the antibody transgene

Allelic Composition	Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0
Genetic Background	C57BL/6-Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(ML5sHEL)5Ccg mutation (2 available)

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

immune system

abnormal immature B cell morphology ( J:109923 )

• there are reduced numbers of immature B cells bearing transgenic IgM in the bone marrow

• expression of IgM is 2- to 5- fold lower than on immature B cells found in mice carrying just the Tg(IghelMD4)4Ccg

abnormal pro-B cell morphology ( J:109923 )

• there are reduced numbers of pro-B cells bearing transgenic IgM in the bone marrow

decreased B cell number ( J:89156 )

• almost all of the B cells express the transgenic antibody

• the number of B cells expressing the transgenic antibody is 30% less than found in singly transgenic mice carrying just the antibody transgene

• this demonstrates that partial deletion occurs of B cells that recognize soluble self antigen

abnormal mature B cell morphology ( J:109923 )

• there is an increased percentage of mature B cells in the bone marrow

abnormal germinal center B cell morphology ( J:109923 )

• B cells expressing the transgenic Ig are absent from the germinal center of the spleen and lymph nodes

abnormal plasma cell morphology ( J:109923 )

• plasma cells producing transgenic Ig are found rarely in these mice

abnormal spleen B cell follicle morphology ( J:109923 )

• splenic B cells bearing transgenic Ig are restricted to the follicular mantle zones

decreased IgM level ( J:78308 , J:89156 )

• very little IgM is detectable in the sera despite the presence of soluble antigen for the transgenic antibody (J:89156)

abnormal B cell anergy ( J:78308 , J:89156 )

• B cells expressing the transgenic antibody are anergic as determined by the lack of HEL specific antibody found in the sera (J:89156)

• anergy occurs both centrally (i.e. in the bone marrow) and in the periphery (J:89156)

• this anergy can be reversed by stimulating B cells in vitro (J:89156)

abnormal central B cell anergy ( J:109923 )

• immature B cells in the bone marrow lack reactivity when transferred to irradiated host mice that are immunized with a HEL antigen

hematopoietic system

abnormal immature B cell morphology ( J:109923 )

• there are reduced numbers of immature B cells bearing transgenic IgM in the bone marrow

• expression of IgM is 2- to 5- fold lower than on immature B cells found in mice carrying just the Tg(IghelMD4)4Ccg

abnormal pro-B cell morphology ( J:109923 )

• there are reduced numbers of pro-B cells bearing transgenic IgM in the bone marrow

decreased B cell number ( J:89156 )

• almost all of the B cells express the transgenic antibody

• the number of B cells expressing the transgenic antibody is 30% less than found in singly transgenic mice carrying just the antibody transgene

• this demonstrates that partial deletion occurs of B cells that recognize soluble self antigen

abnormal mature B cell morphology ( J:109923 )

• there is an increased percentage of mature B cells in the bone marrow

abnormal germinal center B cell morphology ( J:109923 )

• B cells expressing the transgenic Ig are absent from the germinal center of the spleen and lymph nodes

abnormal plasma cell morphology ( J:109923 )

• plasma cells producing transgenic Ig are found rarely in these mice

abnormal spleen B cell follicle morphology ( J:109923 )

• splenic B cells bearing transgenic Ig are restricted to the follicular mantle zones

decreased IgM level ( J:78308 , J:89156 )

• very little IgM is detectable in the sera despite the presence of soluble antigen for the transgenic antibody (J:89156)

Allelic Composition	Tlr4^Lps-d/Tlr4^Lps-d Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C3H/HeJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(KLK4mHEL)6Ccg mutation (2 available)
Tlr4^Lps-d mutation (7 available); any Tlr4 mutation (91 available)

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

hematopoietic system

increased B-1 B cell number ( J:115059 )

• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

decreased B cell number ( J:115059 )

• a 35% reduction in number of recirculating mature autoreactive B cells is observed, compared to wild-type

immune system

increased B-1 B cell number ( J:115059 )

• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

decreased B cell number ( J:115059 )

• a 35% reduction in number of recirculating mature autoreactive B cells is observed, compared to wild-type

Allelic Composition	Lyn^tm1Ard/Lyn⁺ Ptpn6^me-v/Ptpn6⁺ Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lyn^tm1Ard mutation (6 available); any Lyn mutation (65 available)
Ptpn6^me-v mutation (3 available); any Ptpn6 mutation (49 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

hematopoietic system

abnormal mature B cell morphology ( J:110531 )

• mature B cells have about 4-fold lower surface IgM levels

immune system

abnormal mature B cell morphology ( J:110531 )

• mature B cells have about 4-fold lower surface IgM levels

Allelic Composition	Tlr9^tm1Aki/Tlr9^tm1Aki Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(KLK4mHEL)6Ccg mutation (2 available)
Tlr9^tm1Aki mutation (7 available); any Tlr9 mutation (66 available)

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

hematopoietic system

decreased mature B cell number ( J:115059 )

• a 37% reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type

increased B-1 B cell number ( J:115059 )

• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

immune system

decreased mature B cell number ( J:115059 )

• a 37% reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type

increased B-1 B cell number ( J:115059 )

• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

Allelic Composition	Myd88^tm1Aki/Myd88^tm1Aki Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Myd88^tm1Aki mutation (9 available); any Myd88 mutation (52 available)
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(KLK4mHEL)6Ccg mutation (2 available)

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

hematopoietic system

decreased mature B cell number ( J:115059 )

• a reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type

increased B-1 B cell number ( J:115059 )

• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

immune system

decreased mature B cell number ( J:115059 )

• a reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type

increased B-1 B cell number ( J:115059 )

• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

Allelic Composition	Prkcd^tm1Qxu/Prkcd^tm1Qxu Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prkcd^tm1Qxu mutation (0 available); any Prkcd mutation (54 available)
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(KLK4mHEL)6Ccg mutation (2 available)

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

immune system

immune system phenotype ( J:76134 )

N	• mice exhibit the same number of B cells as in Tg(IghelMD4)4Ccg mice indicating normal clonal deletion

Allelic Composition	Prkcd^tm1Qxu/Prkcd^tm1Qxu Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

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

immune system

immune system phenotype ( J:76134 )

N	• B cell activation in vitro and in vivo are normal

decreased B cell number ( J:76134 )

• peripheral B cells are reduced compared to in Prkcd^tm1Qxu/Prkcd^tm1Qxu Tg(IghelMD4)4Ccg mice

abnormal spleen primary B follicle morphology ( J:76134 )

• the number of B follicles is increased compared to in Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

increased spleen germinal center number ( J:76134 )

abnormal B cell physiology ( J:76134 )

• surface levels of IgMa are decreased 2-fold compared to in Prkcd^tm1Qxu/Prkcd^tm1Qxu Tg(IghelMD4)4Ccg mice

abnormal B cell proliferation ( J:76134 )

• B cells proliferate vigorously in response to HEL unlike Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

abnormal self tolerance ( J:76134 )

• B cells switch to an autoreactive phenotype and fail to induce tolerance

• B cells proliferate vigorously in response to HEL unlike Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

autoimmune response ( J:76134 )

• mice exhibit an 80-fold increase in HEL-specific antibodies compared to in Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

hematopoietic system

decreased B cell number ( J:76134 )

• peripheral B cells are reduced compared to in Prkcd^tm1Qxu/Prkcd^tm1Qxu Tg(IghelMD4)4Ccg mice

abnormal spleen primary B follicle morphology ( J:76134 )

• the number of B follicles is increased compared to in Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

increased spleen germinal center number ( J:76134 )

abnormal B cell physiology ( J:76134 )

• surface levels of IgMa are decreased 2-fold compared to in Prkcd^tm1Qxu/Prkcd^tm1Qxu Tg(IghelMD4)4Ccg mice

abnormal B cell proliferation ( J:76134 )

• B cells proliferate vigorously in response to HEL unlike Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

cellular

abnormal B cell proliferation ( J:76134 )

• B cells proliferate vigorously in response to HEL unlike Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

Allelic Composition	Lyn^tm1Ard/Lyn^tm1Ard Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lyn^tm1Ard mutation (6 available); any Lyn mutation (65 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal B cell negative selection ( J:110531 )

• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is blocked at the immature B cell stage instead of anergy inducation in mature B cells as occurs with wild-type bone marrow

abnormal mature B cell morphology ( J:110531 )

• mature B cells have 4-5 lower sIgM levels on their surface

absent B-1 B cells ( J:110531 )

• B1 B cells are absent in these mice

abnormal B cell activation ( J:110531 )

• B cells have altered kinetics of calcium fluxing upon BCR engagement with delayed influx but an ultimately higher peak intracellular concentration

increased IgM level ( J:110531 )

• hypersecretion of the transgenic IgM antibody occurs in these mice

hematopoietic system

abnormal B cell negative selection ( J:110531 )

abnormal mature B cell morphology ( J:110531 )

• mature B cells have 4-5 lower sIgM levels on their surface

absent B-1 B cells ( J:110531 )

• B1 B cells are absent in these mice

abnormal B cell activation ( J:110531 )

• B cells have altered kinetics of calcium fluxing upon BCR engagement with delayed influx but an ultimately higher peak intracellular concentration

increased IgM level ( J:110531 )

• hypersecretion of the transgenic IgM antibody occurs in these mice

Allelic Composition	Lyn^tm1Ard/Lyn⁺ Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lyn^tm1Ard mutation (6 available); any Lyn mutation (65 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal mature B cell morphology ( J:110531 )

• mature B cells have about 2-fold lower surface IgM levels

hematopoietic system

abnormal mature B cell morphology ( J:110531 )

• mature B cells have about 2-fold lower surface IgM levels

Allelic Composition	Ptpn6^me-v/Ptpn6⁺ Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptpn6^me-v mutation (3 available); any Ptpn6 mutation (49 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal mature B cell morphology ( J:110531 )

• mature B cells have about 2-fold lower surface IgM levels

hematopoietic system

abnormal mature B cell morphology ( J:110531 )

• mature B cells have about 2-fold lower surface IgM levels

Allelic Composition	Cd22^tm1Eac/Cd22⁺ Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd22^tm1Eac mutation (1 available); any Cd22 mutation (64 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal mature B cell morphology ( J:110531 )

• expression of CD22 on the surface of cells is half that of controls

• surface expression of IgM is about 70-80% of controls

hematopoietic system

abnormal mature B cell morphology ( J:110531 )

• expression of CD22 on the surface of cells is half that of controls

• surface expression of IgM is about 70-80% of controls

Allelic Composition	Cd22^tm1Eac/Cd22⁺ Lyn^tm1Ard/Lyn⁺ Ptpn6^me-v/Ptpn6⁺ Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd22^tm1Eac mutation (1 available); any Cd22 mutation (64 available)
Lyn^tm1Ard mutation (6 available); any Lyn mutation (65 available)
Ptpn6^me-v mutation (3 available); any Ptpn6 mutation (49 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal B cell negative selection ( J:110531 )

• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is almost completely blocked at the immature B cell stage

abnormal mature B cell morphology ( J:110531 )

• surface expression of IgM is only 15% of controls

increased IgM level ( J:110531 )

• half the mice have a 15-fold increase in Hel-specific serum IgM

hematopoietic system

abnormal B cell negative selection ( J:110531 )

• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is almost completely blocked at the immature B cell stage

abnormal mature B cell morphology ( J:110531 )

• surface expression of IgM is only 15% of controls

increased IgM level ( J:110531 )

• half the mice have a 15-fold increase in Hel-specific serum IgM

Allelic Composition	Cd22^tm1Eac/Cd22⁺ Ptpn6^me-v/Ptpn6⁺ Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd22^tm1Eac mutation (1 available); any Cd22 mutation (64 available)
Ptpn6^me-v mutation (3 available); any Ptpn6 mutation (49 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal B cell negative selection ( J:110531 )

• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is partially blocked at the immature B cell stage

abnormal mature B cell morphology ( J:110531 )

• surface expression of IgM is less than half of controls

hematopoietic system

abnormal B cell negative selection ( J:110531 )

• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is partially blocked at the immature B cell stage

abnormal mature B cell morphology ( J:110531 )

• surface expression of IgM is less than half of controls

Allelic Composition	Cd22^tm1Eac/Cd22⁺ Lyn^tm1Ard/Lyn⁺ Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

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

immune system

abnormal B cell negative selection ( J:110531 )

• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is patially blocked at the immature B cell stage

abnormal mature B cell morphology ( J:110531 )

• surface expression of IgM is less than half of controls

hematopoietic system

abnormal B cell negative selection ( J:110531 )

• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is patially blocked at the immature B cell stage

abnormal mature B cell morphology ( J:110531 )

• surface expression of IgM is less than half of controls

Allelic Composition	Cd19^tm1(cre)Cgn/Cd19^tm1(cre)Cgn Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd19^tm1(cre)Cgn mutation (11 available); any Cd19 mutation (60 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

hematopoietic system

decreased B cell number ( J:155314 )

• modest reduction in peripheral B cell numbers

immune system

immune system phenotype ( J:155314 )

N	• tolerance mechanisms to prevent autoantibody production are intact and B cells are able to selectively downregulate IgM

decreased B cell number ( J:155314 )

• modest reduction in peripheral B cell numbers

Allelic Composition	Cd19^tm1(cre)Cgn/Cd19^tm1(cre)Cgn Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd19^tm1(cre)Cgn mutation (11 available); any Cd19 mutation (60 available)
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(ML5sHEL)5Ccg mutation (2 available)

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

hematopoietic system

decreased B cell number ( J:155314 )

• low splenic and lymph node B cell numbers

immune system

immune system phenotype ( J:155314 )

N	• tolerance mechanisms to prevent autoantibody production are intact and B cells are able to selectively downregulate IgM

decreased B cell number ( J:155314 )

• low splenic and lymph node B cell numbers

Allelic Composition	Card19^tm1Rwen/Card19^tm1Rwen Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Card19^tm1Rwen mutation (0 available); any Card19 mutation (13 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

hematopoietic system

abnormal B cell activation ( J:336763 )

• BCR-induced IkappaBalpha phosporylation is increased in B cells

immune system

abnormal B cell activation ( J:336763 )

• BCR-induced IkappaBalpha phosporylation is increased in B cells

Allelic Composition	Card19^tm1Rwen/Card19^tm1Rwen Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JSfd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Card19^tm1Rwen mutation (0 available); any Card19 mutation (13 available)
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(ML5sHEL)5Ccg mutation (2 available)

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

immune system

increased B cell apoptosis ( J:336763 )

• increased apoptosis of B cells in response to self-antigen HEL or anti-IgM stimulation

decreased B cell proliferation ( J:336763 )

• self-reactive B-cells are less proliferative in response to BCR engagement

decreased B cell number ( J:336763 )

• decrease in the B cell population in the spleen indicating enhanced B cell tolerance

increased B cell number ( J:336763 )

• increase in the frequency of gamma L chain positive splenic B cells compared to transgenic mice wild-type for Card19

hematopoietic system

increased B cell apoptosis ( J:336763 )

• increased apoptosis of B cells in response to self-antigen HEL or anti-IgM stimulation

decreased B cell proliferation ( J:336763 )

• self-reactive B-cells are less proliferative in response to BCR engagement

decreased B cell number ( J:336763 )

• decrease in the B cell population in the spleen indicating enhanced B cell tolerance

increased B cell number ( J:336763 )

• increase in the frequency of gamma L chain positive splenic B cells compared to transgenic mice wild-type for Card19

cellular

increased B cell apoptosis ( J:336763 )

• increased apoptosis of B cells in response to self-antigen HEL or anti-IgM stimulation

decreased B cell proliferation ( J:336763 )

• self-reactive B-cells are less proliferative in response to BCR engagement

Allelic Composition	Fnip1^{Gt(RRM154)Byg}/Fnip1^{Gt(RRM154)Byg} Tg(IghelMD4)4Ccg/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fnip1^{Gt(RRM154)Byg} mutation (0 available); any Fnip1 mutation (60 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

increased immature B cell number ( J:189078 )

• in the bone marrow compared with Fnip1^tm1.2Tes or Fnip1^{Gt(RRM154)Byg} homozygotes

decreased B-1 B cell number ( J:189078 )

absent B-2 B cells ( J:189078 )

absent B cells ( J:189078 )

• absence of peripheral B cells

hematopoietic system

increased immature B cell number ( J:189078 )

• in the bone marrow compared with Fnip1^tm1.2Tes or Fnip1^{Gt(RRM154)Byg} homozygotes

decreased B-1 B cell number ( J:189078 )

absent B-2 B cells ( J:189078 )

absent B cells ( J:189078 )

• absence of peripheral B cells

Allelic Composition	Cd79b^tm1Mnz/Cd79b^tm1Mnz Tg(IghelMD4)4Ccg/0 Tg(Rag2-Igb)1Mnz/0
Genetic Background	involves: 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd79b^tm1Mnz mutation (0 available); any Cd79b mutation (36 available)
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(Rag2-Igb)1Mnz mutation (0 available)

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

hematopoietic system

abnormal immature B cell morphology ( J:78601 )

• increase in apoptosis of immature B cells

arrested B cell differentiation ( J:78601 )

• B cells fail to develop beyond the IgM^low immature B cell stage and no mature recirculating CD25^-IgM^high B cells are seen

immune system

abnormal immature B cell morphology ( J:78601 )

• increase in apoptosis of immature B cells

arrested B cell differentiation ( J:78601 )

• B cells fail to develop beyond the IgM^low immature B cell stage and no mature recirculating CD25^-IgM^high B cells are seen

Allelic Composition	Cd79b^tm1Mnz/Cd79b^tm1Mnz Tg(BCL2)22Wehi/0 Tg(IghelMD4)4Ccg/0 Tg(Rag2-Igb)1Mnz/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * C57BL/6JWehi * SJL/JWehi

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd79b^tm1Mnz mutation (0 available); any Cd79b mutation (36 available)
Tg(BCL2)22Wehi mutation (2 available)
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(Rag2-Igb)1Mnz mutation (0 available)

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

hematopoietic system

arrested B cell differentiation ( J:78601 )

• expression of Tg(BCL2)22Wehi rescues immature B cell apoptosis but immature B cell differentiation beyond the IgM^low immature B cell stage is still impaired and no mature recirculating CD25^-IgM^high B cells are seen

immune system

arrested B cell differentiation ( J:78601 )

Allelic Composition	Endou^tm1Tft/Endou^tm1Tft Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0
Genetic Background	involves: 129S/SvEv * C57BL/6 * C57BL/6JSfd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Endou^tm1Tft mutation (0 available); any Endou mutation (29 available)
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(ML5sHEL)5Ccg mutation (2 available)

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

immune system

immune system phenotype ( J:208364 )

N	• B cell phenotypes observed in Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice are normalized

decreased activation-induced B cell apoptosis ( J:208364 )

• absent in high responder mice

increased autoantibody level ( J:208364 )

• increased anti-HEL auto-antibody production compared with control mice

cellular

decreased activation-induced B cell apoptosis ( J:208364 )

• absent in high responder mice

hematopoietic system

decreased activation-induced B cell apoptosis ( J:208364 )

• absent in high responder mice

Allelic Composition	Cr2^{tm2.1(HLA-A)Crr}/Cr2^{tm2.1(HLA-A)Crr} Tg(IghelMD4)4Ccg/?
Genetic Background	involves: C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cr2^{tm2.1(HLA-A)Crr} mutation (0 available); any Cr2 mutation (84 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal B cell activation ( J:151991 )

• B cells fail to react to sub-optimal doses of antigen coated in C3 complement

• B cells are also unresponsive to a suboptimal level of anti-IgM, anti-CD40, and C3d

hematopoietic system

abnormal B cell activation ( J:151991 )

• B cells fail to react to sub-optimal doses of antigen coated in C3 complement

• B cells are also unresponsive to a suboptimal level of anti-IgM, anti-CD40, and C3d

Allelic Composition	Tg(IghelMD4)4Ccg/? Tg(KLK4mHEL)6Ccg/?
Genetic Background	involves: C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(KLK4mHEL)6Ccg mutation (2 available)

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

immune system

increased immature B cell number ( J:78307 )

• a small increase occurs in the number of B220^low immature B cells found in the bone marrow

arrested B cell differentiation ( J:78307 )

• the immature B cells found in the bone marrow have low surface expression of IgM suggesting B cells have encountered antigen but failed to develop to a mature phenotype

decreased mature B cell number ( J:78307 )

• mature B cells are reduced 5- to 20- fold in the bone marrow, spleen and lymph node

• the small number of mature B cells present have B cell receptors encoded by endogenous heavy chain

hematopoietic system

increased immature B cell number ( J:78307 )

• a small increase occurs in the number of B220^low immature B cells found in the bone marrow

arrested B cell differentiation ( J:78307 )

• the immature B cells found in the bone marrow have low surface expression of IgM suggesting B cells have encountered antigen but failed to develop to a mature phenotype

decreased mature B cell number ( J:78307 )

• mature B cells are reduced 5- to 20- fold in the bone marrow, spleen and lymph node

• the small number of mature B cells present have B cell receptors encoded by endogenous heavy chain

Allelic Composition	Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0
Genetic Background	involves: C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(ML5sHEL)5Ccg mutation (2 available)

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

immune system

decreased B cell number ( J:76134 )

• peripheral B cells are reduced compared to in Tg(IghelMD4)4Ccg mice

decreased marginal zone B cell number ( J:132538 )

• very few B cells in the spleen have surface markers indicative of the marginal zone phenotype

abnormal spleen primary B follicle morphology ( J:76134 )

• the number of B follicles is decreased compared to in Tg(IghelMD4)4Ccg mice

abnormal B cell physiology ( J:76134 )

• surface levels of IgMa are decreased 7- to 11-fold compared to in Tg(IghelMD4)4Ccg mice

abnormal B cell anergy ( J:73608 , J:132538 )

• B cells from these mice are unable to activate HEL-specific CD4 T cells from Tg(TcrHEL3A9)1Mmd mice when co-cultured together in the presence of HEL protein (J:73608)

• B cells are anergic when stimulated with HEL antigen as determined by reduced antibody production, no upregulation of activation markers CD69 and CD86, and failure to increase size (J:132538)

hematopoietic system

decreased B cell number ( J:76134 )

• peripheral B cells are reduced compared to in Tg(IghelMD4)4Ccg mice

decreased marginal zone B cell number ( J:132538 )

• very few B cells in the spleen have surface markers indicative of the marginal zone phenotype

abnormal spleen primary B follicle morphology ( J:76134 )

• the number of B follicles is decreased compared to in Tg(IghelMD4)4Ccg mice

abnormal B cell physiology ( J:76134 )

• surface levels of IgMa are decreased 7- to 11-fold compared to in Tg(IghelMD4)4Ccg mice

Allelic Composition	Atp11c^ambr/Y Tg(IghelMD4)4Ccg/0
Genetic Background	involves: C57BL/6 * C57BL/6JApb

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Atp11c^ambr mutation (2 available); any Atp11c mutation (16 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

hematopoietic system

decreased immature B cell number ( J:171924 )

• immature B cell numbers are partially rescued compared to in Atp11c^ambr hemizygotes

decreased pro-B cell number ( J:171924 )

• pro-B cell numbers are partially rescued compared to in Tg(IghelMD4)4Ccg mice

immune system

decreased immature B cell number ( J:171924 )

• immature B cell numbers are partially rescued compared to in Atp11c^ambr hemizygotes

decreased pro-B cell number ( J:171924 )

• pro-B cell numbers are partially rescued compared to in Tg(IghelMD4)4Ccg mice

Allelic Composition	Fnip1^tm1.2Baba/Fnip1^tm1.2Baba Tg(IghelMD4)4Ccg/0
Genetic Background	involves: C57BL/6 * C57BL/6J * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fnip1^tm1.2Baba mutation (0 available); any Fnip1 mutation (60 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

hematopoietic system

increased immature B cell number ( J:189078 )

• in the bone marrow compared with Fnip1^tm1.2Tes or Fnip1^{Gt(RRM154)Byg} homozygotes

decreased B-1 B cell number ( J:189078 )

absent B-2 B cells ( J:189078 )

absent B cells ( J:189078 )

• absence of peripheral B cells

immune system

increased immature B cell number ( J:189078 )

• in the bone marrow compared with Fnip1^tm1.2Tes or Fnip1^{Gt(RRM154)Byg} homozygotes

decreased B-1 B cell number ( J:189078 )

absent B-2 B cells ( J:189078 )

absent B cells ( J:189078 )

• absence of peripheral B cells

Allelic Composition	Bcl6^tm1.1Toka/Bcl6^tm1.1Toka Tg(IghelMD4)4Ccg/0
Genetic Background	involves: C57BL/6 * NZB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bcl6^tm1.1Toka mutation (1 available); any Bcl6 mutation (57 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

increased activation-induced B cell apoptosis ( J:174014 )

• B cells co-transferred with Tg(TcraTcrb)425Cbn cells into wild-type mice immunized with HEL-ovalbumin exhibit increased apoptosis compared with similarly treated heterozygous cells

abnormal germinal center B cell physiology ( J:174014 )

• B cells co-transferred with Tg(TcraTcrb)425Cbn cells into wild-type mice immunized with HEL-ovalbumin exhibit impaired formation of germinal center B cell populations compared with similarly treated heterozygous cells

cellular

increased activation-induced B cell apoptosis ( J:174014 )

• B cells co-transferred with Tg(TcraTcrb)425Cbn cells into wild-type mice immunized with HEL-ovalbumin exhibit increased apoptosis compared with similarly treated heterozygous cells

hematopoietic system

increased activation-induced B cell apoptosis ( J:174014 )

• B cells co-transferred with Tg(TcraTcrb)425Cbn cells into wild-type mice immunized with HEL-ovalbumin exhibit increased apoptosis compared with similarly treated heterozygous cells

abnormal germinal center B cell physiology ( J:174014 )

Allelic Composition	Tg(IghelMD4)4Ccg/0 Tg(KLK4mHEL)6Ccg/0
Genetic Background	NOD.B6-Tg(IghelMD4)4Ccg Tg(KLK4mHEL)6Ccg/Dvs

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(KLK4mHEL)6Ccg mutation (2 available)

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

immune system

decreased B cell number ( J:89156 )

• the number of B cells found in the spleen is decreased by more than 6-fold compared to NOD mice carrying just the antibody transgene

• very few of the remaining B cells expresses the transgenic antibody

• the number of B cells expressing the transgenic antibody is 1.1% of that found in singly transgenic NOD mice carrying only the antibody transgene

hematopoietic system

decreased B cell number ( J:89156 )

• the number of B cells found in the spleen is decreased by more than 6-fold compared to NOD mice carrying just the antibody transgene

• very few of the remaining B cells expresses the transgenic antibody

• the number of B cells expressing the transgenic antibody is 1.1% of that found in singly transgenic NOD mice carrying only the antibody transgene

Allelic Composition	Tg(IghelMD4)4Ccg/0 Tg(ML5sHEL)5Ccg/0
Genetic Background	NOD.B6-Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg/Dvs

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)
Tg(ML5sHEL)5Ccg mutation (2 available)

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

immune system

abnormal B cell morphology ( J:89156 )

• there is no decrease in the number of B cells expressing the transgenic antibody compared to singly transgenic NOD mice that carry just the antibody transgene

• this suggests defect in the NOD strain of deleting B cells that recognize soluble self antigens

abnormal B cell clonal deletion ( J:89156 )

• Background Sensitivity: the normal number of B cells found in these mice demonstrate a defect in the NOD strain of deleting B cells that recognize soluble self antigens

decreased IgM level ( J:89156 )

• very little IgM is detectable in the sera despite the presence of soluble antigen for the transgenic antibody

abnormal B cell anergy ( J:89156 )

• B cells expressing the transgenic antibody are anergic as determined by the lack of HEL specific antibody found in the sera

• anergy occurs both centrally (i.e. in the bone marrow) and in the periphery

• this anergy can be reversed by stimulating B cells in vitro

• when compared to singly transgenic controls, antibody production following BCR and CD40 stimulation is less suppressed in doubly transgenic NOD mice than in doubly transgenic C57BL/6 mice (2.6-fold less vs 4.5 fold less)

hematopoietic system

abnormal B cell morphology ( J:89156 )

• there is no decrease in the number of B cells expressing the transgenic antibody compared to singly transgenic NOD mice that carry just the antibody transgene

• this suggests defect in the NOD strain of deleting B cells that recognize soluble self antigens

abnormal B cell clonal deletion ( J:89156 )

• Background Sensitivity: the normal number of B cells found in these mice demonstrate a defect in the NOD strain of deleting B cells that recognize soluble self antigens

decreased IgM level ( J:89156 )

• very little IgM is detectable in the sera despite the presence of soluble antigen for the transgenic antibody

Allelic Composition	Ighm^tm1Cgn/Ighm^tm1Cgn Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg
Genetic Background	NOD.Cg-Ighm^tm1Cgn Tg(IghelMD4)4Ccg/DvsJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ighm^tm1Cgn mutation (17 available); any Ighm mutation (56 available)
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal T cell proliferation ( J:80859 )

• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD

insulitis ( J:80859 )

• mice have low levels of insulitis starting at 12 weeks of age with a mean disease score of 1.62 compared to non-transgenic NOD mice that have a mean score of 3.01 at this age

decreased CD8-positive, alpha-beta T cell number ( J:80859 )

• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice

abnormal mature B cell morphology ( J:80859 )

• the number but not the proportion of B cells found in the spleen is twice that of non-transgenic NOD mice

• all of the B cells express the transgenic IgM B cell receptor specific for hen egg lysozyme

abnormal B lymphocyte antigen presentation ( J:80859 )

• purified B cells fail to stimulate T cells from non-transgenic NOD mice when cultured together in the presence of the diabetes autoantigen GAD

decreased susceptibility to autoimmune diabetes ( J:80859 )

• 16.7% of female mice develop diabetes by 21 weeks of age compared to control NOD mice that have an incidence rate of 95.5% at this age

• mice with lymphosarcomas were not included in the analysis

neoplasm

increased lymphoma incidence ( J:80859 )

• lymphosarcomas are present in the majority of mice with development starting at 20 weeks of age

hematopoietic system

abnormal T cell proliferation ( J:80859 )

• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD

decreased CD8-positive, alpha-beta T cell number ( J:80859 )

• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice

abnormal mature B cell morphology ( J:80859 )

• the number but not the proportion of B cells found in the spleen is twice that of non-transgenic NOD mice

• all of the B cells express the transgenic IgM B cell receptor specific for hen egg lysozyme

abnormal B lymphocyte antigen presentation ( J:80859 )

• purified B cells fail to stimulate T cells from non-transgenic NOD mice when cultured together in the presence of the diabetes autoantigen GAD

endocrine/exocrine glands

insulitis ( J:80859 )

• mice have low levels of insulitis starting at 12 weeks of age with a mean disease score of 1.62 compared to non-transgenic NOD mice that have a mean score of 3.01 at this age

cellular

abnormal T cell proliferation ( J:80859 )

• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	type 1 diabetes mellitus	DOID:9744	OMIM:222100	J:80859

Allelic Composition	Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg
Genetic Background	involves: C57BL/6

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Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

decreased pro-B cell number ( J:171924 )

decreased pre-B cell number ( J:171924 )

hematopoietic system

decreased pro-B cell number ( J:171924 )

decreased pre-B cell number ( J:171924 )

Allelic Composition	Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg
Genetic Background	NOD.B6-Tg(IghelMD4)4Ccg/DvsJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal T cell proliferation ( J:80859 )

• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD

decreased CD8-positive, alpha-beta T cell number ( J:80859 )

• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice

abnormal mature B cell morphology ( J:80859 , J:89156 )

• the number but not the proportion of B cells found in the spleen is twice that of non-transgenic NOD mice (J:80859)

• 99.3% of these B cells express the transgenic IgM B cell receptor specific for hen egg lysozyme (J:80859)

• 8.4% of the B cells express endogenous IgM indicating there is some escape from allelic exclusion (J:80859)

• 98% of the B cells express the transgenic antibody that is specific for hen egg lysozyme (HEL) (J:89156)

• 94% of these B cells retain the ability to bind HEL protein (J:89156)

increased susceptibility to autoimmune diabetes ( J:80859 )

• 90% of female mice are diabetic by 30 weeks of age which is similar to the incidence rate in non-transgenic NOD mice

• there is a significant delay in time of onset compared to non-transgenic diabetic mice

hematopoietic system

abnormal T cell proliferation ( J:80859 )

• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD

decreased CD8-positive, alpha-beta T cell number ( J:80859 )

• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice

abnormal mature B cell morphology ( J:80859 , J:89156 )

• the number but not the proportion of B cells found in the spleen is twice that of non-transgenic NOD mice (J:80859)

• 99.3% of these B cells express the transgenic IgM B cell receptor specific for hen egg lysozyme (J:80859)

• 8.4% of the B cells express endogenous IgM indicating there is some escape from allelic exclusion (J:80859)

• 98% of the B cells express the transgenic antibody that is specific for hen egg lysozyme (HEL) (J:89156)

• 94% of these B cells retain the ability to bind HEL protein (J:89156)

cellular

abnormal T cell proliferation ( J:80859 )

• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:80859

Allelic Composition	Tg(IghelMD4)4Ccg/0
Genetic Background	C57BL/6-Tg(IghelMD4)4Ccg

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

abnormal B cell morphology ( J:78308 , J:109923 , J:132538 )

• most peripheral B cells express the transgenic immunoglobulin (Ig) that binds hen egg lysozyme peptide (HEL) with a high affinity (J:109923)

• the few B cells expressing endogenous Ig in the spleen express high levels of IgM with little to no levels of IgD compared to splenic B cells from wild-type mice that are IgM^low IgD^high (J:109923)

• over 90% of B cells express immunoglobulin that has a high affinity for hen egg lysozyme antigen (HEL) (J:132538)

abnormal immature B cell morphology ( J:109923 )

• there are reduced numbers of immature B cells bearing transgenic IgM in the bone marrow

increased immature B cell number ( J:78308 , J:132538 )

• three quarters of the B cells in the spleen are immature as indicated by the IgM^hi IgD^hi surface markers (J:78308)

• three quarters of the B cells in the spleen are immature as indicated by the IgM^hi IgD^hi surface markers (J:132538)

abnormal pro-B cell morphology ( J:109923 )

• there are reduced numbers of pro-B cells bearing transgenic IgM in the bone marrow

abnormal mature B cell morphology ( J:89156 , J:109923 )

• 98% of the B cells express the transgenic antibody that is specific for hen egg lysozyme (HEL) (J:89156)

• 94% of these B cells retain the ability to bind HEL protein (J:89156)

• there is an increased percentage of mature B cells in the bone marrow (J:109923)

abnormal B-2 B cell morphology ( J:132538 )

• all of the B cells found in the peritoneal cavity are of the B-2 lineage as determined by B220^hi CD5^lowexpression

abnormal germinal center B cell morphology ( J:109923 )

• B cells expressing the transgenic Ig are absent from the germinal center of the spleen and lymph nodes

abnormal plasma cell morphology ( J:109923 )

• plasma cells bearing endogenous Ig outnumber plasma cells bearing the transgenic Ig

increased IgG2b level ( J:132538 )

• there are low levels of anti-HEL IgG2b in the sera of unimmunized mice

increased IgM level ( J:78308 , J:132538 )

• there are high levels of anti-HEL IgM in the sera of unimmunized mice (J:78308)

• there are high levels of anti-HEL IgM in the sera of unimmunized mice (J:132538)

hematopoietic system

abnormal B cell morphology ( J:78308 , J:109923 , J:132538 )

• most peripheral B cells express the transgenic immunoglobulin (Ig) that binds hen egg lysozyme peptide (HEL) with a high affinity (J:109923)

• over 90% of B cells express immunoglobulin that has a high affinity for hen egg lysozyme antigen (HEL) (J:132538)

abnormal immature B cell morphology ( J:109923 )

• there are reduced numbers of immature B cells bearing transgenic IgM in the bone marrow

increased immature B cell number ( J:78308 , J:132538 )

• three quarters of the B cells in the spleen are immature as indicated by the IgM^hi IgD^hi surface markers (J:78308)

• three quarters of the B cells in the spleen are immature as indicated by the IgM^hi IgD^hi surface markers (J:132538)

abnormal pro-B cell morphology ( J:109923 )

• there are reduced numbers of pro-B cells bearing transgenic IgM in the bone marrow

abnormal mature B cell morphology ( J:89156 , J:109923 )

• 98% of the B cells express the transgenic antibody that is specific for hen egg lysozyme (HEL) (J:89156)

• 94% of these B cells retain the ability to bind HEL protein (J:89156)

• there is an increased percentage of mature B cells in the bone marrow (J:109923)

abnormal B-2 B cell morphology ( J:132538 )

• all of the B cells found in the peritoneal cavity are of the B-2 lineage as determined by B220^hi CD5^lowexpression

abnormal germinal center B cell morphology ( J:109923 )

• B cells expressing the transgenic Ig are absent from the germinal center of the spleen and lymph nodes

abnormal plasma cell morphology ( J:109923 )

• plasma cells bearing endogenous Ig outnumber plasma cells bearing the transgenic Ig

increased IgG2b level ( J:132538 )

• there are low levels of anti-HEL IgG2b in the sera of unimmunized mice

increased IgM level ( J:78308 , J:132538 )

• there are high levels of anti-HEL IgM in the sera of unimmunized mice (J:78308)

• there are high levels of anti-HEL IgM in the sera of unimmunized mice (J:132538)

Allelic Composition	Tg(IghelMD4)4Ccg/0
Genetic Background	involves: C3H/HeJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)

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

hematopoietic system

decreased pro-B cell number ( J:115059 )

• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

decreased pre-B cell number ( J:115059 )

• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

immune system

decreased pro-B cell number ( J:115059 )

• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

decreased pre-B cell number ( J:115059 )

• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

Allelic Composition	Tg(IghelMD4)4Ccg/0
Genetic Background	involves: C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(IghelMD4)4Ccg mutation (3 available)

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

immune system

decreased pro-B cell number ( J:115059 )

• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

decreased pre-B cell number ( J:115059 )

• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

abnormal B cell activation ( J:73608 )

• B cells become activated when cultured with HEL protein and CD4 T cells from Tg(TcrHEL3A9)1Mmd transgenic mice

• B cells in this culture quickly upregulate CD44 and CD86

• by 48 hours in culture, B cells are greatly enlarged as they undergo blastogenesis

• B cells cultured without the T cells initially upregulate activation markers but then die

• when HEL peptide is used in culture, some B cells increase expression of activation markers but do not form large blast cells

hematopoietic system

decreased pro-B cell number ( J:115059 )

• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

decreased pre-B cell number ( J:115059 )

• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

abnormal B cell activation ( J:73608 )

• B cells become activated when cultured with HEL protein and CD4 T cells from Tg(TcrHEL3A9)1Mmd transgenic mice

• B cells in this culture quickly upregulate CD44 and CD86

• by 48 hours in culture, B cells are greatly enlarged as they undergo blastogenesis

• B cells cultured without the T cells initially upregulate activation markers but then die

• when HEL peptide is used in culture, some B cells increase expression of activation markers but do not form large blast cells

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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