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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
Cd19tm1(cre)Cgn/Cd19+
Ptentm1Hwu/Ptentm1Hwu
Tg(IghelMD4)4Ccg/0
Tg(ML5sHEL)5Ccg/0
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 MGI:5007685
cn2
Dicer1tm1Mmk/Dicer1tm1Mmk
Tg(IghelMD4)4Ccg/0
Cd79atm1(cre)Reth/Cd79a+
involves: BALB/c MGI:3797394
cn3
Cd79atm1(cre)Reth/Cd79a+
Phf5atm1.1Oux/Phf5atm1.1Oux
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
Tlr4Lps-d/Tlr4Lps-d
Tg(IghelMD4)4Ccg/0
Tg(KLK4mHEL)6Ccg/0
involves: 129P2/OlaHsd * C3H/HeJ * C57BL/6 MGI:3694809
cx7
Lyntm1Ard/Lyn+
Ptpn6me-v/Ptpn6+
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3852087
cx8
Tlr9tm1Aki/Tlr9tm1Aki
Tg(IghelMD4)4Ccg/0
Tg(KLK4mHEL)6Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3694807
cx9
Myd88tm1Aki/Myd88tm1Aki
Tg(IghelMD4)4Ccg/0
Tg(KLK4mHEL)6Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3694808
cx10
Prkcdtm1Qxu/Prkcdtm1Qxu
Tg(IghelMD4)4Ccg/0
Tg(KLK4mHEL)6Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3841844
cx11
Prkcdtm1Qxu/Prkcdtm1Qxu
Tg(IghelMD4)4Ccg/0
Tg(ML5sHEL)5Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3841845
cx12
Lyntm1Ard/Lyntm1Ard
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3852084
cx13
Lyntm1Ard/Lyn+
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3852085
cx14
Ptpn6me-v/Ptpn6+
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3852086
cx15
Cd22tm1Eac/Cd22+
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3852088
cx16
Cd22tm1Eac/Cd22+
Lyntm1Ard/Lyn+
Ptpn6me-v/Ptpn6+
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3852089
cx17
Cd22tm1Eac/Cd22+
Ptpn6me-v/Ptpn6+
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3852090
cx18
Cd22tm1Eac/Cd22+
Lyntm1Ard/Lyn+
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:3852091
cx19
Cd19tm1(cre)Cgn/Cd19tm1(cre)Cgn
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:5007683
cx20
Cd19tm1(cre)Cgn/Cd19tm1(cre)Cgn
Tg(IghelMD4)4Ccg/0
Tg(ML5sHEL)5Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:5007684
cx21
Card19tm1Rwen/Card19tm1Rwen
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 MGI:7514984
cx22
Card19tm1Rwen/Card19tm1Rwen
Tg(IghelMD4)4Ccg/0
Tg(ML5sHEL)5Ccg/0
involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JSfd MGI:7514963
cx23
Fnip1Gt(RRM154)Byg/Fnip1Gt(RRM154)Byg
Tg(IghelMD4)4Ccg/0
involves: 129P2/OlaHsd * C57BL/6 * FVB/N * SJL MGI:5445166
cx24
Cd79btm1Mnz/Cd79btm1Mnz
Tg(IghelMD4)4Ccg/0
Tg(Rag2-Igb)1Mnz/0
involves: 129S1/Sv * C57BL/6 MGI:4453800
cx25
Cd79btm1Mnz/Cd79btm1Mnz
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
Endoutm1Tft/Endoutm1Tft
Tg(IghelMD4)4Ccg/0
Tg(ML5sHEL)5Ccg/0
involves: 129S/SvEv * C57BL/6 * C57BL/6JSfd MGI:5582909
cx27
Cr2tm2.1(HLA-A)Crr/Cr2tm2.1(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
Atp11cambr/Y
Tg(IghelMD4)4Ccg/0
involves: C57BL/6 * C57BL/6JApb MGI:5006965
cx31
Fnip1tm1.2Baba/Fnip1tm1.2Baba
Tg(IghelMD4)4Ccg/0
involves: C57BL/6 * C57BL/6J * FVB/N * SJL MGI:5445165
cx32
Bcl6tm1.1Toka/Bcl6tm1.1Toka
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
Ighmtm1Cgn/Ighmtm1Cgn
Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg
NOD.Cg-Ighmtm1Cgn 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


Genotype
MGI:5007685
cn1
Allelic
Composition
Cd19tm1(cre)Cgn/Cd19+
Ptentm1Hwu/Ptentm1Hwu
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:
Cd19tm1(cre)Cgn mutation (11 available); any Cd19 mutation (56 available)
Ptentm1Hwu mutation (16 available); any Pten mutation (81 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
• 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




Genotype
MGI:3797394
cn2
Allelic
Composition
Dicer1tm1Mmk/Dicer1tm1Mmk
Tg(IghelMD4)4Ccg/0
Cd79atm1(cre)Reth/Cd79a+
Genetic
Background
involves: BALB/c
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd79atm1(cre)Reth mutation (3 available); any Cd79a mutation (22 available)
Dicer1tm1Mmk mutation (0 available); any Dicer1 mutation (94 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• while B cell numbers are increased relative to in Cd79atm1(cre)Reth/Cd79a+ Dicer1tm1Mmk/Dicer1tm1Mmk mice, numbers are still lower than in wild-type mice

hematopoietic system
• while B cell numbers are increased relative to in Cd79atm1(cre)Reth/Cd79a+ Dicer1tm1Mmk/Dicer1tm1Mmk mice, numbers are still lower than in wild-type mice




Genotype
MGI:7611733
cn3
Allelic
Composition
Cd79atm1(cre)Reth/Cd79a+
Phf5atm1.1Oux/Phf5atm1.1Oux
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:
Cd79atm1(cre)Reth mutation (3 available); any Cd79a mutation (22 available)
Phf5atm1.1Oux mutation (0 available); any Phf5a mutation (18 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• addition of a pre-rearranged IgH transgene partially but significantly increases the number of CD19+ B cells

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




Genotype
MGI:3793443
cx4
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
• 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
• 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




Genotype
MGI:3793461
cx5
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
• 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
• there are reduced numbers of pro-B cells bearing transgenic IgM in the bone marrow
• 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
• there is an increased percentage of mature B cells in the bone marrow
• B cells expressing the transgenic Ig are absent from the germinal center of the spleen and lymph nodes
• plasma cells producing transgenic Ig are found rarely in these mice
• splenic B cells bearing transgenic Ig are restricted to the follicular mantle zones
• very little IgM is detectable in the sera despite the presence of soluble antigen for the transgenic antibody (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)
• immature B cells in the bone marrow lack reactivity when transferred to irradiated host mice that are immunized with a HEL antigen

hematopoietic system
• 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
• there are reduced numbers of pro-B cells bearing transgenic IgM in the bone marrow
• 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
• there is an increased percentage of mature B cells in the bone marrow
• B cells expressing the transgenic Ig are absent from the germinal center of the spleen and lymph nodes
• plasma cells producing transgenic Ig are found rarely in these mice
• splenic B cells bearing transgenic Ig are restricted to the follicular mantle zones
• very little IgM is detectable in the sera despite the presence of soluble antigen for the transgenic antibody (J:89156)




Genotype
MGI:3694809
cx6
Allelic
Composition
Tlr4Lps-d/Tlr4Lps-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)
Tlr4Lps-d mutation (7 available); any Tlr4 mutation (90 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants
• a 35% reduction in number of recirculating mature autoreactive B cells is observed, compared to wild-type

immune system
• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants
• a 35% reduction in number of recirculating mature autoreactive B cells is observed, compared to wild-type




Genotype
MGI:3852087
cx7
Allelic
Composition
Lyntm1Ard/Lyn+
Ptpn6me-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:
Lyntm1Ard mutation (6 available); any Lyn mutation (64 available)
Ptpn6me-v mutation (3 available); any Ptpn6 mutation (47 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• mature B cells have about 4-fold lower surface IgM levels

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




Genotype
MGI:3694807
cx8
Allelic
Composition
Tlr9tm1Aki/Tlr9tm1Aki
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)
Tlr9tm1Aki mutation (7 available); any Tlr9 mutation (65 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• a 37% reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type
• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

immune system
• a 37% reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type
• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants




Genotype
MGI:3694808
cx9
Allelic
Composition
Myd88tm1Aki/Myd88tm1Aki
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:
Myd88tm1Aki mutation (9 available); any Myd88 mutation (50 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
• a reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type
• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants

immune system
• a reduction in number of recirculating mature autoreactive B cells is observed compared to wild-type
• more B1 cells are detected among peritoneal lymphocytes in double transgenic mutants compared to Tg(IghelMD4)4Ccg single transgenic mutants




Genotype
MGI:3841844
cx10
Allelic
Composition
Prkcdtm1Qxu/Prkcdtm1Qxu
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:
Prkcdtm1Qxu mutation (0 available); any Prkcd 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
immune system
N
• mice exhibit the same number of B cells as in Tg(IghelMD4)4Ccg mice indicating normal clonal deletion




Genotype
MGI:3841845
cx11
Allelic
Composition
Prkcdtm1Qxu/Prkcdtm1Qxu
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:
Prkcdtm1Qxu mutation (0 available); any Prkcd mutation (52 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
N
• B cell activation in vitro and in vivo are normal
• peripheral B cells are reduced compared to in Prkcdtm1Qxu/Prkcdtm1Qxu Tg(IghelMD4)4Ccg mice
• the number of B follicles is increased compared to in Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice
• surface levels of IgMa are decreased 2-fold compared to in Prkcdtm1Qxu/Prkcdtm1Qxu Tg(IghelMD4)4Ccg mice
• B cells proliferate vigorously in response to HEL unlike Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice
• 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
• mice exhibit an 80-fold increase in HEL-specific antibodies compared to in Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

hematopoietic system
• peripheral B cells are reduced compared to in Prkcdtm1Qxu/Prkcdtm1Qxu Tg(IghelMD4)4Ccg mice
• the number of B follicles is increased compared to in Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice
• surface levels of IgMa are decreased 2-fold compared to in Prkcdtm1Qxu/Prkcdtm1Qxu Tg(IghelMD4)4Ccg mice
• B cells proliferate vigorously in response to HEL unlike Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice

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




Genotype
MGI:3852084
cx12
Allelic
Composition
Lyntm1Ard/Lyntm1Ard
Tg(IghelMD4)4Ccg/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lyntm1Ard mutation (6 available); any Lyn mutation (64 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• 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
• mature B cells have 4-5 lower sIgM levels on their surface
• B1 B cells are absent in these mice
• B cells have altered kinetics of calcium fluxing upon BCR engagement with delayed influx but an ultimately higher peak intracellular concentration
• hypersecretion of the transgenic IgM antibody occurs in these mice

hematopoietic system
• 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
• mature B cells have 4-5 lower sIgM levels on their surface
• B1 B cells are absent in these mice
• B cells have altered kinetics of calcium fluxing upon BCR engagement with delayed influx but an ultimately higher peak intracellular concentration
• hypersecretion of the transgenic IgM antibody occurs in these mice




Genotype
MGI:3852085
cx13
Allelic
Composition
Lyntm1Ard/Lyn+
Tg(IghelMD4)4Ccg/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lyntm1Ard mutation (6 available); any Lyn mutation (64 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• mature B cells have about 2-fold lower surface IgM levels

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




Genotype
MGI:3852086
cx14
Allelic
Composition
Ptpn6me-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:
Ptpn6me-v mutation (3 available); any Ptpn6 mutation (47 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• mature B cells have about 2-fold lower surface IgM levels

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




Genotype
MGI:3852088
cx15
Allelic
Composition
Cd22tm1Eac/Cd22+
Tg(IghelMD4)4Ccg/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd22tm1Eac mutation (1 available); any Cd22 mutation (63 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• 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
• expression of CD22 on the surface of cells is half that of controls
• surface expression of IgM is about 70-80% of controls




Genotype
MGI:3852089
cx16
Allelic
Composition
Cd22tm1Eac/Cd22+
Lyntm1Ard/Lyn+
Ptpn6me-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:
Cd22tm1Eac mutation (1 available); any Cd22 mutation (63 available)
Lyntm1Ard mutation (6 available); any Lyn mutation (64 available)
Ptpn6me-v mutation (3 available); any Ptpn6 mutation (47 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• 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
• surface expression of IgM is only 15% of controls
• half the mice have a 15-fold increase in Hel-specific serum IgM

hematopoietic system
• 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
• surface expression of IgM is only 15% of controls
• half the mice have a 15-fold increase in Hel-specific serum IgM




Genotype
MGI:3852090
cx17
Allelic
Composition
Cd22tm1Eac/Cd22+
Ptpn6me-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:
Cd22tm1Eac mutation (1 available); any Cd22 mutation (63 available)
Ptpn6me-v mutation (3 available); any Ptpn6 mutation (47 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is partially blocked at the immature B cell stage
• surface expression of IgM is less than half of controls

hematopoietic system
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is partially blocked at the immature B cell stage
• surface expression of IgM is less than half of controls




Genotype
MGI:3852091
cx18
Allelic
Composition
Cd22tm1Eac/Cd22+
Lyntm1Ard/Lyn+
Tg(IghelMD4)4Ccg/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd22tm1Eac mutation (1 available); any Cd22 mutation (63 available)
Lyntm1Ard mutation (6 available); any Lyn mutation (64 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is patially blocked at the immature B cell stage
• surface expression of IgM is less than half of controls

hematopoietic system
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is patially blocked at the immature B cell stage
• surface expression of IgM is less than half of controls




Genotype
MGI:5007683
cx19
Allelic
Composition
Cd19tm1(cre)Cgn/Cd19tm1(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:
Cd19tm1(cre)Cgn mutation (11 available); any Cd19 mutation (56 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• modest reduction in peripheral B cell numbers

immune system
N
• tolerance mechanisms to prevent autoantibody production are intact and B cells are able to selectively downregulate IgM
• modest reduction in peripheral B cell numbers




Genotype
MGI:5007684
cx20
Allelic
Composition
Cd19tm1(cre)Cgn/Cd19tm1(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:
Cd19tm1(cre)Cgn mutation (11 available); any Cd19 mutation (56 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
• low splenic and lymph node B cell numbers

immune system
N
• tolerance mechanisms to prevent autoantibody production are intact and B cells are able to selectively downregulate IgM
• low splenic and lymph node B cell numbers




Genotype
MGI:7514984
cx21
Allelic
Composition
Card19tm1Rwen/Card19tm1Rwen
Tg(IghelMD4)4Ccg/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Card19tm1Rwen 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
• BCR-induced IkappaBalpha phosporylation is increased in B cells

immune system
• BCR-induced IkappaBalpha phosporylation is increased in B cells




Genotype
MGI:7514963
cx22
Allelic
Composition
Card19tm1Rwen/Card19tm1Rwen
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:
Card19tm1Rwen 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 apoptosis of B cells in response to self-antigen HEL or anti-IgM stimulation
• self-reactive B-cells are less proliferative in response to BCR engagement
• decrease in the B cell population in the spleen indicating enhanced B cell tolerance
• increase in the frequency of gamma L chain positive splenic B cells compared to transgenic mice wild-type for Card19

hematopoietic system
• increased apoptosis of B cells in response to self-antigen HEL or anti-IgM stimulation
• self-reactive B-cells are less proliferative in response to BCR engagement
• decrease in the B cell population in the spleen indicating enhanced B cell tolerance
• increase in the frequency of gamma L chain positive splenic B cells compared to transgenic mice wild-type for Card19

cellular
• increased apoptosis of B cells in response to self-antigen HEL or anti-IgM stimulation
• self-reactive B-cells are less proliferative in response to BCR engagement




Genotype
MGI:5445166
cx23
Allelic
Composition
Fnip1Gt(RRM154)Byg/Fnip1Gt(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:
Fnip1Gt(RRM154)Byg mutation (0 available); any Fnip1 mutation (59 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• in the bone marrow compared with Fnip1tm1.2Tes or Fnip1Gt(RRM154)Byg homozygotes
• absence of peripheral B cells

hematopoietic system
• in the bone marrow compared with Fnip1tm1.2Tes or Fnip1Gt(RRM154)Byg homozygotes
• absence of peripheral B cells




Genotype
MGI:4453800
cx24
Allelic
Composition
Cd79btm1Mnz/Cd79btm1Mnz
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:
Cd79btm1Mnz 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
• increase in apoptosis of immature B cells
• B cells fail to develop beyond the IgMlow immature B cell stage and no mature recirculating CD25-IgMhigh B cells are seen

immune system
• increase in apoptosis of immature B cells
• B cells fail to develop beyond the IgMlow immature B cell stage and no mature recirculating CD25-IgMhigh B cells are seen




Genotype
MGI:4453802
cx25
Allelic
Composition
Cd79btm1Mnz/Cd79btm1Mnz
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:
Cd79btm1Mnz 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
• expression of Tg(BCL2)22Wehi rescues immature B cell apoptosis but immature B cell differentiation beyond the IgMlow immature B cell stage is still impaired and no mature recirculating CD25-IgMhigh B cells are seen

immune system
• expression of Tg(BCL2)22Wehi rescues immature B cell apoptosis but immature B cell differentiation beyond the IgMlow immature B cell stage is still impaired and no mature recirculating CD25-IgMhigh B cells are seen




Genotype
MGI:5582909
cx26
Allelic
Composition
Endoutm1Tft/Endoutm1Tft
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:
Endoutm1Tft mutation (0 available); any Endou mutation (28 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
N
• B cell phenotypes observed in Tg(IghelMD4)4Ccg Tg(ML5sHEL)5Ccg mice are normalized
• absent in high responder mice
• increased anti-HEL auto-antibody production compared with control mice

cellular
• absent in high responder mice

hematopoietic system
• absent in high responder mice




Genotype
MGI:4356056
cx27
Allelic
Composition
Cr2tm2.1(HLA-A)Crr/Cr2tm2.1(HLA-A)Crr
Tg(IghelMD4)4Ccg/?
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cr2tm2.1(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
• 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
• 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




Genotype
MGI:3799746
cx28
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
• a small increase occurs in the number of B220low immature B cells found in the bone marrow
• 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
• 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
• a small increase occurs in the number of B220low immature B cells found in the bone marrow
• 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
• 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




Genotype
MGI:3799370
cx29
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
• peripheral B cells are reduced compared to in Tg(IghelMD4)4Ccg mice
• very few B cells in the spleen have surface markers indicative of the marginal zone phenotype
• the number of B follicles is decreased compared to in Tg(IghelMD4)4Ccg mice
• surface levels of IgMa are decreased 7- to 11-fold compared to in Tg(IghelMD4)4Ccg mice
• 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
• peripheral B cells are reduced compared to in Tg(IghelMD4)4Ccg mice
• very few B cells in the spleen have surface markers indicative of the marginal zone phenotype
• the number of B follicles is decreased compared to in Tg(IghelMD4)4Ccg mice
• surface levels of IgMa are decreased 7- to 11-fold compared to in Tg(IghelMD4)4Ccg mice




Genotype
MGI:5006965
cx30
Allelic
Composition
Atp11cambr/Y
Tg(IghelMD4)4Ccg/0
Genetic
Background
involves: C57BL/6 * C57BL/6JApb
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Atp11cambr 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
• immature B cell numbers are partially rescued compared to in Atp11cambr hemizygotes
• pro-B cell numbers are partially rescued compared to in Tg(IghelMD4)4Ccg mice

immune system
• immature B cell numbers are partially rescued compared to in Atp11cambr hemizygotes
• pro-B cell numbers are partially rescued compared to in Tg(IghelMD4)4Ccg mice




Genotype
MGI:5445165
cx31
Allelic
Composition
Fnip1tm1.2Baba/Fnip1tm1.2Baba
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:
Fnip1tm1.2Baba mutation (0 available); any Fnip1 mutation (59 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• in the bone marrow compared with Fnip1tm1.2Tes or Fnip1Gt(RRM154)Byg homozygotes
• absence of peripheral B cells

immune system
• in the bone marrow compared with Fnip1tm1.2Tes or Fnip1Gt(RRM154)Byg homozygotes
• absence of peripheral B cells




Genotype
MGI:5140809
cx32
Allelic
Composition
Bcl6tm1.1Toka/Bcl6tm1.1Toka
Tg(IghelMD4)4Ccg/0
Genetic
Background
involves: C57BL/6 * NZB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bcl6tm1.1Toka mutation (1 available); any Bcl6 mutation (55 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• 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
• 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
• 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
• 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
• 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




Genotype
MGI:3793442
cx33
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
• 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
• 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




Genotype
MGI:3793444
cx34
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
• 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
• 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
• very little IgM is detectable in the sera despite the presence of soluble antigen for the transgenic antibody
• 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
• 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
• 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
• very little IgM is detectable in the sera despite the presence of soluble antigen for the transgenic antibody




Genotype
MGI:3793299
cx35
Allelic
Composition
Ighmtm1Cgn/Ighmtm1Cgn
Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg
Genetic
Background
NOD.Cg-Ighmtm1Cgn Tg(IghelMD4)4Ccg/DvsJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ighmtm1Cgn mutation (17 available); any Ighm mutation (55 available)
Tg(IghelMD4)4Ccg mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD
• 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
• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice
• 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
• purified B cells fail to stimulate T cells from non-transgenic NOD mice when cultured together in the presence of the diabetes autoantigen GAD
• 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
• lymphosarcomas are present in the majority of mice with development starting at 20 weeks of age

hematopoietic system
• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD
• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice
• 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
• 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
• 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
• 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




Genotype
MGI:5006966
tg36
Allelic
Composition
Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg
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

hematopoietic system




Genotype
MGI:3793301
tg37
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
• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD
• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice
• 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)
• 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
• T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD
• the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice
• 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
• 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




Genotype
MGI:3793440
tg38
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
• 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 IgMlow IgDhigh (J:109923)
• over 90% of B cells express immunoglobulin that has a high affinity for hen egg lysozyme antigen (HEL) (J:132538)
• there are reduced numbers of immature B cells bearing transgenic IgM in the bone marrow
• three quarters of the B cells in the spleen are immature as indicated by the IgMhi IgDhi surface markers (J:78308)
• three quarters of the B cells in the spleen are immature as indicated by the IgMhi IgDhi surface markers (J:132538)
• there are reduced numbers of pro-B cells bearing transgenic IgM in the bone marrow
• 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)
• all of the B cells found in the peritoneal cavity are of the B-2 lineage as determined by B220hi CD5lowexpression
• B cells expressing the transgenic Ig are absent from the germinal center of the spleen and lymph nodes
• plasma cells bearing endogenous Ig outnumber plasma cells bearing the transgenic Ig
• there are low levels of anti-HEL IgG2b in the sera of unimmunized mice
• 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
• 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 IgMlow IgDhigh (J:109923)
• over 90% of B cells express immunoglobulin that has a high affinity for hen egg lysozyme antigen (HEL) (J:132538)
• there are reduced numbers of immature B cells bearing transgenic IgM in the bone marrow
• three quarters of the B cells in the spleen are immature as indicated by the IgMhi IgDhi surface markers (J:78308)
• three quarters of the B cells in the spleen are immature as indicated by the IgMhi IgDhi surface markers (J:132538)
• there are reduced numbers of pro-B cells bearing transgenic IgM in the bone marrow
• 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)
• all of the B cells found in the peritoneal cavity are of the B-2 lineage as determined by B220hi CD5lowexpression
• B cells expressing the transgenic Ig are absent from the germinal center of the spleen and lymph nodes
• plasma cells bearing endogenous Ig outnumber plasma cells bearing the transgenic Ig
• there are low levels of anti-HEL IgG2b in the sera of unimmunized mice
• 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)




Genotype
MGI:3694805
tg39
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
• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background
• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background

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




Genotype
MGI:3694806
tg40
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
• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background
• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background
• 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
• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background
• bone marrow contains fewer combined numbers of combined pro-pre B cells than on a B6 background
• 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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last database update
04/09/2024
MGI 6.23
The Jackson Laboratory