Phenotypes associated with this allele
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nr4a1tm1Pcn mutation
(0 available);
any
Nr4a1 mutation
(39 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
cellular
|
|
• greater proliferation of CD45.2+ B cells when co-cultured for 72 hours with congenically marked wild-type CD45.1+ lymphocytes and anti-immunoglobulin M (anti-IgM)
|
hematopoietic system
|
|
• greater proliferation of CD45.2+ B cells when co-cultured for 72 hours with congenically marked wild-type CD45.1+ lymphocytes and anti-immunoglobulin M (anti-IgM)
|
immune system
|
|
• greater proliferation of CD45.2+ B cells when co-cultured for 72 hours with congenically marked wild-type CD45.1+ lymphocytes and anti-immunoglobulin M (anti-IgM)
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igh-Jtm1Cgn mutation
(3 available);
any
Igh-J mutation
(13 available)
Ightm4Cgn mutation
(0 available);
any
Igh mutation
(43 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
immune system
|
|
• mice lack mature BCR positive B cells
|
hematopoietic system
|
|
• mice lack mature BCR positive B cells
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Syktm1.2Tara mutation
(1 available);
any
Syk mutation
(42 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
hematopoietic system
|
|
• mature B cells exhibit a follicular B cell-like phenotype
|
immune system
|
|
• mature B cells exhibit a follicular B cell-like phenotype
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo1tm1.1Rdp mutation
(0 available);
any
Foxo1 mutation
(31 available)
Igh-Jtm1Cgn mutation
(3 available);
any
Igh-J mutation
(13 available)
Ightm4Cgn mutation
(0 available);
any
Igh mutation
(43 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
immune system
|
|
• mice exhibit a limited rescue of IgM negative B cells compared to in Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
|
hematopoietic system
|
|
• mice exhibit a limited rescue of IgM negative B cells compared to in Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
|
immune system
|
|
• mice exhibit an accumulation of IgM negative B cells compared to in Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
• mice exhibit an efficient rescue of BCR negative B cells compared with Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
• however, follicle B cells are rescued compared to in Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
|
hematopoietic system
|
|
• mice exhibit an accumulation of IgM negative B cells compared to in Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
• mice exhibit an efficient rescue of BCR negative B cells compared with Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
• however, follicle B cells are rescued compared to in Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Cr2-cre)3Cgn mutation
(2 available)
Xrcc4tm1Fwa mutation
(0 available);
any
Xrcc4 mutation
(25 available)
Xrcc4tm2Fwa mutation
(0 available);
any
Xrcc4 mutation
(25 available)
|
|
|
cellular
|
|
• genomic stability is disrupted in activated B cells with chromosome breakage occurring in close to half of cells
• B cells undergoing class switch recombination have even greater increased risk of chromosome breakage due to aberrations at the Igh locus
• there is also increased breakage at the Igk and Igl loci with 1% of stimulated B cells demonstrating this
• Igl breaks in activated B cells are frequently fused to AID-dependent Igh breaks in the same cell to form chromosome 12/16 translocations
• there is also a five-fold increase in Igh-Myc translocations activated B cells compared to controls
|
hematopoietic system
|
|
• class switch recombination often leads to chromosome breakage at the Igh locus
|
immune system
|
|
• class switch recombination often leads to chromosome breakage at the Igh locus
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rag2tm1Cgn mutation
(2 available);
any
Rag2 mutation
(117 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
Xrcc4tm1Fwa mutation
(0 available);
any
Xrcc4 mutation
(25 available)
Xrcc4tm2Fwa mutation
(0 available);
any
Xrcc4 mutation
(25 available)
|
|
|
cellular
|
|
• genomic stability is disrupted in activated B cells with chromosome breakage occurring in close to half of cells
• B cells undergoing class switch recombination have even greater increased risk of chromosome breakage due to aberrations at the Igh locus
• there is decreased breakage at Igl locus compared to conditional knockouts on a Rag-sufficient background
|
hematopoietic system
|
|
• class switch recombination often leads to chromosome breakage at the Igh locus
|
immune system
|
|
• class switch recombination often leads to chromosome breakage at the Igh locus
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
Xrcc4tm1Fwa mutation
(0 available);
any
Xrcc4 mutation
(25 available)
Xrcc4tm2Fwa mutation
(0 available);
any
Xrcc4 mutation
(25 available)
|
|
|
cellular
|
|
• genomic stability is disrupted in activated B cells with chromosome breakage occurring in close to half of cells
• however, there is no increased breakage of the Igh locus compared to wild-type controls
• there is increased breakage at the Igk and Igl loci with 1% of stimulated B cells demonstrating this
|
immune system
|
N |
• architecture of all secondary lymphoid organs is similar to wild-type
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd79atm4.1Cgn mutation
(1 available);
any
Cd79a mutation
(22 available)
Cd79atm4Cgn mutation
(0 available);
any
Cd79a mutation
(22 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
hematopoietic system
|
|
• B cell numbers are reduced 50% in the bone marrow, by about 2/3 in follicular and marginal zones of the spleen, and strongly reduced in the inguinal lymph nodes
• B cell half life is about 3 - 6 days
|
|
|
• B cell surface IgD levels are decreased about 100 fold on around 1/3 and 1/2 of spleen or inguinal lymph node B cells, respectively
|
|
|
• B cell surface IgM levels are decreased about 30 fold on around 1/3 and 1/2 of spleen or inguinal lymph node B cells, respectively
|
immune system
|
|
• B cell numbers are reduced 50% in the bone marrow, by about 2/3 in follicular and marginal zones of the spleen, and strongly reduced in the inguinal lymph nodes
• B cell half life is about 3 - 6 days
|
|
|
• B cell surface IgD levels are decreased about 100 fold on around 1/3 and 1/2 of spleen or inguinal lymph node B cells, respectively
|
|
|
• B cell surface IgM levels are decreased about 30 fold on around 1/3 and 1/2 of spleen or inguinal lymph node B cells, respectively
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd79atm5.1Cgn mutation
(0 available);
any
Cd79a mutation
(22 available)
Cd79atm5Cgn mutation
(0 available);
any
Cd79a mutation
(22 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
hematopoietic system
|
|
• B cell numbers are reduced 50% in the bone marrow, by about 2/3 in follicular and marginal zones of the spleen, and strongly reduced in the inguinal lymph nodes
|
immune system
|
|
• B cell numbers are reduced 50% in the bone marrow, by about 2/3 in follicular and marginal zones of the spleen, and strongly reduced in the inguinal lymph nodes
|
immune system
|
|
• mice exhibit a very limited rescue of BCR negative B cells in several lymphoid organs compared with Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
|
hematopoietic system
|
|
• mice exhibit a very limited rescue of BCR negative B cells in several lymphoid organs compared with Igh-Jtm1Cgn/Ightm4Cgn Tg(Cr2-cre)3Cgn mice
|
immune system
|
|
• mice lack mature BCR positive B cells
|
hematopoietic system
|
|
• mice lack mature BCR positive B cells
|
immune system
|
|
• mice lack mature BCR positive B cells
|
hematopoietic system
|
|
• mice lack mature BCR positive B cells
|
immune system
|
N |
• mice exhibit a restoration of normal IgG1 levels in B cells compared with Mir146tm1.1Tmmc Tg(Cr2-cre)3Cgn mice
|
|
|
• following immunization with sheep red blood cells in mixed bone marrow chimeras
|
hematopoietic system
|
|
• following immunization with sheep red blood cells in mixed bone marrow chimeras
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dclre1ctm2.1Jpdv mutation
(1 available);
any
Dclre1c mutation
(30 available)
Dclre1ctm2.2Jpdv mutation
(0 available);
any
Dclre1c mutation
(30 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
immune system
|
N |
• mice exhibit normal B cell development and Ig titers
|
|
|
• class switching to IgG3 is decreased 23% compared to in wild-type mice
• in vivo Ig switching to IgA on KLH immunization is reduced 52% compared to in similarly treated wild-type mice
• class switch recombination junctions are altered compared to in wild-type mice
|
hematopoietic system
|
|
• class switching to IgG3 is decreased 23% compared to in wild-type mice
• in vivo Ig switching to IgA on KLH immunization is reduced 52% compared to in similarly treated wild-type mice
• class switch recombination junctions are altered compared to in wild-type mice
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4tm1Fwa mutation
(1 available);
any
Lig4 mutation
(44 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
Xrcc4tm2Fwa mutation
(0 available);
any
Xrcc4 mutation
(25 available)
|
|
|
immune system
|
|
• class switching to IgG1 is 20% to 50% of wild-type
• class switching to IgG3 is 50% of wild-type
• IgH class switching is reduced compared to in wild-type B cells
|
cellular
|
|
• B cell stimulated with anti-CD40 and IL4 exhibit metaphase chromosome breaks unlike similarly treated wild-type cells
|
hematopoietic system
|
|
• class switching to IgG1 is 20% to 50% of wild-type
• class switching to IgG3 is 50% of wild-type
• IgH class switching is reduced compared to in wild-type B cells
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prkar1atm2Gsm mutation
(1 available);
any
Prkar1a mutation
(19 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
immune system
|
|
• following stimulation with LPS and LPS plus IL4, splenic B cells exhibit impaired class switch recombination compared with wild-type cells
• however, stimulated B cell proliferation is normal
|
hematopoietic system
|
|
• following stimulation with LPS and LPS plus IL4, splenic B cells exhibit impaired class switch recombination compared with wild-type cells
• however, stimulated B cell proliferation is normal
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm2(Lmp1/CD40)Uzs mutation
(0 available);
any
Gt(ROSA)26Sor mutation
(944 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
immune system
|
|
• mice exhibit the same immune phenotype as in Gt(ROSA)26Sortm2(Lmp1/CD40)Uzs Cd19tm1(cre)Cgn double heterozygotes
|
|
|
• mice exhibit the same immune phenotype as in Gt(ROSA)26Sortm2(Lmp1/CD40)Uzs Cd19tm1(cre)Cgn double heterozygotes
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mef2btm2Rdf mutation
(0 available);
any
Mef2b mutation
(22 available)
Tg(BCL2/IGH)M23Tjd mutation
(0 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
neoplasm
|
|
• plasmablastic lymphoma (PBL) in 20% of mice at age 17-18 months after chronic immunization with sheep red blood cells (SRBCs)
|
|
|
• in 40% of mice at age 17-18 months after chronic immunization with sheep red blood cells (SRBCs)
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mir146tm1.1Lfl mutation
(1 available);
any
Mir146 mutation
(9 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
immune system
|
|
• minimal in young un-immunized mice on GL7+PNA+, which is further exacerbated with age
• at 6 months of age in un-immunized mice
• in young mice immunized with sheep red blood cells
|
|
|
• in young mice immunized with sheep red blood cells
|
|
|
• at 6 months of age in un-immunized mice
• in young mice immunized with sheep red blood cells
|
|
|
• SRBC-specific in young mice immunized with sheep red blood cells (SRBC)
|
|
|
• following immunization with 4-hydroxy-3-nitrophenyl linked to Keyhole Limpet Hemocyanin (KLH) (NP-KLH) in alum
|
|
|
• at 6 months of age in un-immunized mice
|
hematopoietic system
|
|
• minimal in young un-immunized mice on GL7+PNA+, which is further exacerbated with age
• at 6 months of age in un-immunized mice
• in young mice immunized with sheep red blood cells
|
|
|
• in young mice immunized with sheep red blood cells
|
|
|
• at 6 months of age in un-immunized mice
• in young mice immunized with sheep red blood cells
|
|
|
• SRBC-specific in young mice immunized with sheep red blood cells (SRBC)
|
|
|
• following immunization with 4-hydroxy-3-nitrophenyl linked to Keyhole Limpet Hemocyanin (KLH) (NP-KLH) in alum
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mef2btm2Rdf mutation
(0 available);
any
Mef2b mutation
(22 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
hematopoietic system
|
|
• observed occasionally at age 17-18 months after chronic immunization with sheep red blood cells (SRBCs)
|
|
|
• increased GC B cell number 10 days after immunization with sheep red blood cells (SRBCs)
• normal non-GC B cell numbers 10 days after immunization with sheep red blood cells (SRBCs)
|
|
|
• 10 days after immunization with sheep red blood cells (SRBCs)
|
immune system
|
|
• observed occasionally at age 17-18 months after chronic immunization with sheep red blood cells (SRBCs)
|
|
|
• increased GC B cell number 10 days after immunization with sheep red blood cells (SRBCs)
• normal non-GC B cell numbers 10 days after immunization with sheep red blood cells (SRBCs)
|
|
|
• 10 days after immunization with sheep red blood cells (SRBCs)
|
|
|
• at age 17-18 months after chronic immunization with sheep red blood cells (SRBCs)
|
|
|
• in 28% of mice at age 17-18 months after chronic immunization with sheep red blood cells (SRBCs)
|
neoplasm
|
|
• at age 17-18 months after chronic immunization with sheep red blood cells (SRBCs)
|
growth/size/body
|
|
• observed occasionally at age 17-18 months after chronic immunization with sheep red blood cells (SRBCs)
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rev3ltm1.1Rsky mutation
(0 available);
any
Rev3l mutation
(118 available)
Rev3ltm1Rsky mutation
(1 available);
any
Rev3l mutation
(118 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
Chromosome aberrations in B cells of Rev3ltm1Rsky/Rev3ltm1.1Rsky Tg(Cr2-cre)3Cgn/0 mice
cellular
|
|
• B cells stimulated in vitro in the presence of LPS or LPS + IL-4 have reduced cellular proliferation compared to controls
• viability of stimulated cells drops dramatically three days after stimulation
|
|
|
• B cells undergoing class switch recombination have a 4-fold greater frequency of irregular chromosomes (broken chromosomes, chromosome fusions, and translocations) than controls
• many of these chromosome breaks occur at the IgH locus
• when B cells are activated without class switch recombination, there is still an increased frequency of chromosome breaks but none occur at the IgH locus
|
immune system
|
|
• B cells stimulated in vitro in the presence of LPS or LPS + IL-4 have reduced cellular proliferation compared to controls
• viability of stimulated cells drops dramatically three days after stimulation
|
|
|
• there is a 2-3 fold reduced frequency of B cells that switch to IgG3 or IgG1 when stimulated in vitro in the presence of LPS or LPS + IL-4, respectively, as compared to controls
• this reduced class switch recombination is still observed when comparisons are made between B cells that have undergone the same number of divisions
• S-mu switch regions have less somatic mutations than controls due to mutant cells having less opportunity to accumulate mutations before switching
|
|
|
• the percentage of mutations that occur in the recombined IgH locus of germinal center B cells is roughly half that of controls
• the mutation percentage drops to less than a third of controls when germinal center B cells are pre-screened to keep only those that have excised the floxed allele
• almost 50% of all sequences derived from these cells contained only one mutation, whereas close to 80% of the sequences derived from controls had multiple mutations
|
|
|
• there is a 2-3 fold reduction in the number of germinal center B cells
• this population is slightly enriched for cells that have escaped cre-mediated deletion of the floxed allele
|
|
|
• sera levels of antigen-specific IgG1 and Iglambda are half that of controls after immunization
|
hematopoietic system
|
|
• B cells stimulated in vitro in the presence of LPS or LPS + IL-4 have reduced cellular proliferation compared to controls
• viability of stimulated cells drops dramatically three days after stimulation
|
|
|
• there is a 2-3 fold reduced frequency of B cells that switch to IgG3 or IgG1 when stimulated in vitro in the presence of LPS or LPS + IL-4, respectively, as compared to controls
• this reduced class switch recombination is still observed when comparisons are made between B cells that have undergone the same number of divisions
• S-mu switch regions have less somatic mutations than controls due to mutant cells having less opportunity to accumulate mutations before switching
|
|
|
• the percentage of mutations that occur in the recombined IgH locus of germinal center B cells is roughly half that of controls
• the mutation percentage drops to less than a third of controls when germinal center B cells are pre-screened to keep only those that have excised the floxed allele
• almost 50% of all sequences derived from these cells contained only one mutation, whereas close to 80% of the sequences derived from controls had multiple mutations
|
|
|
• there is a 2-3 fold reduction in the number of germinal center B cells
• this population is slightly enriched for cells that have escaped cre-mediated deletion of the floxed allele
|
|
|
• sera levels of antigen-specific IgG1 and Iglambda are half that of controls after immunization
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm7(Pik3ca*,EGFP)Rsky mutation
(1 available);
any
Gt(ROSA)26Sor mutation
(944 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
mortality/aging
|
|
• mice die soon after birth
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ebf1tm1.1Rug mutation
(0 available);
any
Ebf1 mutation
(73 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
immune system
hematopoietic system
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lig4tm3.1Fwa mutation
(0 available);
any
Lig4 mutation
(44 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
immune system
hematopoietic system
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igh-Jtm1Cgn mutation
(3 available);
any
Igh-J mutation
(13 available)
Ightm4Cgn mutation
(0 available);
any
Igh mutation
(43 available)
Tg(Cr2-cre)3Cgn mutation
(2 available)
|
|
|
hematopoietic system
|
|
• B cell numbers are reduced 50% in the bone marrow, by about 2/3 in follicular and marginal zones of the spleen, and strongly reduced in the inguinal lymph nodes
|
immune system
|
|
• B cell numbers are reduced 50% in the bone marrow, by about 2/3 in follicular and marginal zones of the spleen, and strongly reduced in the inguinal lymph nodes
|
Analysis Tools