Analysis Tools|
Allele Symbol Allele Name Allele ID |
Igh+ wild type MGI:3045893 |
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| Summary |
65 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• despite the rearrangement, mice exhibit normal non-autoantibody B cell development and function
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• mice exhibit an increase in the number of autoantibody B cells in the spleen, lymph node and peripheral blood compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 16% of heterozygotes die within 1 year, due to lymphomas
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• complete disruption of normal architecture by monomorphic population of medium-sized lymphoid cells
• tumor cells are found outside the capsule
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• majority of moribund mice have a huge thymus
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• cellularity is reduced to ~60% of wild-type level
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• most tumor cells are CD4+CD8+ with varying contribution by CD8 single positive cells
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• under non-competitive conditions, pro-B cell compartment is increased 2-fold relative to wild-type mice
• B cell numbers normalize at later developmental stages
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• T-cell development is partially blocked at the earliest pro-T cell stage
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• absolute numbers are significantly lower than in wild-type
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• absolute numbers are significantly lower than in wild-type
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• complete disruption of normal architecture by monomorphic population of medium-sized lymphoid cells
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• all diseased mice show splenomegaly
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• complete disruption of normal architecture by monomorphic population of medium-sized lymphoid cells
• tumor cells are found outside the capsule
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• all diseased mice show lymphadenopathy
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• complete disruption of normal architecture by monomorphic population of medium-sized lymphoid cells
• tumor cells are found outside the capsule
|
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• majority of moribund mice have a huge thymus
|
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• cellularity is reduced to ~60% of wild-type level
|
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• most tumor cells are CD4+CD8+ with varying contribution by CD8 single positive cells
|
|
• under non-competitive conditions, pro-B cell compartment is increased 2-fold relative to wild-type mice
• B cell numbers normalize at later developmental stages
|
|
• T-cell development is partially blocked at the earliest pro-T cell stage
|
|
• absolute numbers are significantly lower than in wild-type
|
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• absolute numbers are significantly lower than in wild-type
|
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• complete disruption of normal architecture by monomorphic population of medium-sized lymphoid cells
|
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• all diseased mice show splenomegaly
|
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• mice develop lymphoma with a longer latency and at lower incidence than homozygotes
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• most tumor cells are CD4+CD8+ with varying contribution by CD8 single positive cells
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• extensive tumor infiltrates are found in the heart in moribund mice
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• extensive tumor infiltrates are seen in salivary glands in moribund mice
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• extensive tumor infiltrates are seen in salivary glands in moribund mice
|
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• complete disruption of normal architecture by monomorphic population of medium-sized lymphoid cells
• tumor cells are found outside the capsule
|
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• majority of moribund mice have a huge thymus
|
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• cellularity is reduced to ~60% of wild-type level
|
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• most tumor cells are CD4+CD8+ with varying contribution by CD8 single positive cells
|
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• extensive tumor infiltrates are found in the liver in moribund mice
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• extensive tumor infiltrates are found in kidneys of moribund mice
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• extensive tumor infiltrates are found in lungs in moribund mice
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• all diseased mice show splenomegaly
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 13% of B cells in the spleen express IgG1 opposed to less than 1% for wild-type mice
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• 13% of B cells in the spleen express IgG1 opposed to less than 1% for wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 0.4% of B cells in the spleen produce immunoglobulins with high affinity for hen egg lysozyme antigen (HEL)
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• about 0.4% of B cells in the spleen produce immunoglobulins with high affinity for hen egg lysozyme antigen (HEL)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slightly
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• slightly
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• preferentially promoted development to marginal zone B cell
• inefficiently drives bone marrow B lymphopoiesis and follicular B cell development
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• B cell compartment in mutant bone marrow was heterogeneous
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• B cell compartment in mutant spleen was heterogeneous
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• preferentially promoted development to marginal zone B cell
• inefficiently drives bone marrow B lymphopoiesis and follicular B cell development
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• B cell compartment in mutant spleen was heterogeneous
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• preferentially promoted development to marginal zone B cell
• inefficiently drives bone marrow B lymphopoiesis and follicular B cell development
|
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• B cell compartment in mutant bone marrow was heterogeneous
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• B cell compartment in mutant spleen was heterogeneous
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• preferentially promoted development to marginal zone B cell
• inefficiently drives bone marrow B lymphopoiesis and follicular B cell development
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• B cell compartment in mutant spleen was heterogeneous
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type
|
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• reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 2-4 month old mice, majority of B cells are B-2 cells, expressing high levels of IgD and B220; these cells do not express CD5 which is found on T and B-1 cells
|
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• in 2-4 month old mice, majority of B cells are B-2 cells, expressing high levels of IgD and B220; these cells do not express CD5 which is found on T and B-1 cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type
|
|
• reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• there is a break in allelic exclusion in 10% of IgM+ B cells in the bone marrow, 20% of 10% of IgM+ B cells, and 50% of IgM+ B cells in the peritoneum
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• 5% of immature B cells in the bone marrow have a break in allelic exclusion
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• the percentage of B cells expressing lambda light chain is about 3 times higher than in wild-type mice
• this increase in lamda-light chain expression only occurs among B cells demonstrating allelic exclusion (i.e. not expressing both the knock-in and endogenous heavy chain alleles)
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• 15% of mature B cells in the bone marrow, and 20% in the spleen, have a break in allelic exclusion
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• almost all B-1a B cells in the peritoneum express immunoglobulin heavy chains from both alleles (i.e. have a break in allelic exclusion)
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• there is a break in allelic exclusion in 10% of IgM+ B cells in the bone marrow, 20% of 10% of IgM+ B cells, and 50% of IgM+ B cells in the peritoneum
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• 5% of immature B cells in the bone marrow have a break in allelic exclusion
|
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• the percentage of B cells expressing lambda light chain is about 3 times higher than in wild-type mice
• this increase in lamda-light chain expression only occurs among B cells demonstrating allelic exclusion (i.e. not expressing both the knock-in and endogenous heavy chain alleles)
|
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• 15% of mature B cells in the bone marrow, and 20% in the spleen, have a break in allelic exclusion
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• almost all B-1a B cells in the peritoneum express immunoglobulin heavy chains from both alleles (i.e. have a break in allelic exclusion)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the percentage of B cells expressing lambda light chain is about 2 times higher than in wild-type mice
|
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• the percentage of B cells expressing lambda light chain is about 2 times higher than in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the expansion of a monoclonal B cell population in a small percentage of mice is indicative of leukemia
|
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• spleen size is increased with age in a small percentage of mice
|
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• a small percentage of mice have a large population of monoclonal B cells that emerges with age
• these monoclonal B cells are larger in size and number, and have clumped chromatin with little cytoplasm
|
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• a small percentage of mice have increased B cells in the blood due to the emergence of a monoclonal population
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• about 60% of mice with a monoclonal B cell population display lymph node hyperplasia with numbers being up to 15 fold higher than controls
|
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• spleen size is increased with age in a small percentage of mice
|
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• a small percentage of mice have a large population of monoclonal B cells that emerges with age
• these monoclonal B cells are larger in size and number, and have clumped chromatin with little cytoplasm
|
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• a small percentage of mice have increased B cells in the blood due to the emergence of a monoclonal population
|
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• spleen size is increased with age in a small percentage of mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| chronic lymphocytic leukemia | DOID:1040 |
OMIM:109543 OMIM:151400 OMIM:609630 OMIM:612557 OMIM:612558 OMIM:612559 |
J:150315 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the expansion of a monoclonal B cell population in these mice is indicative of leukemia
|
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• spleen size is increased with age due to the emergence of a monoclonal B cell population
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• as mice age, a large population emerges of monoclonal B cells preferentially expressing the wild-type allele
• these monoclonal B cells are larger in size and number, and have clumped chromatin with little cytoplasm
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• as mice age, the number of B cells in the blood increase due to the emergence of a monoclonal population
|
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• about 60% of mice with a monoclonal B cell population display lymph node hyperplasia with numbers being up to 15 fold higher
|
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• spleen size is increased with age due to the emergence of a monoclonal B cell population
|
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• as mice age, a large population emerges of monoclonal B cells preferentially expressing the wild-type allele
• these monoclonal B cells are larger in size and number, and have clumped chromatin with little cytoplasm
|
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• as mice age, the number of B cells in the blood increase due to the emergence of a monoclonal population
|
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• spleen size is increased with age due to the emergence of a monoclonal B cell population
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| chronic lymphocytic leukemia | DOID:1040 |
OMIM:109543 OMIM:151400 OMIM:609630 OMIM:612557 OMIM:612558 OMIM:612559 |
J:150315 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a low but significant level of IgAa is detected in the serum of heterozygotes but is absent in C57BL/6 controls and abundant in BALB/c controls
• IgAa producing plasmocytes are present in heterozygotes but are absent in C57BL/6 controls and abundant in BALB/c controls
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• heterozygotes do not express IgMa
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• a low but significant level of IgAa is detected in the serum of heterozygotes but is absent in C57BL/6 controls and abundant in BALB/c controls
• IgAa producing plasmocytes are present in heterozygotes but are absent in C57BL/6 controls and abundant in BALB/c controls
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• heterozygotes do not express IgMa
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal B cell populations in the bone marrow and spleen
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• mice exhibit a reduction in the ratio of pre-B to pro-B cells compared with wild-type mice
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• in the bone marrow
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• mice exhibit a reduction in the ratio of pre-B to pro-B cells compared with wild-type mice
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• in the bone marrow
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a reduction in the ratio of pre-B to pro-B cells compared with wild-type mice
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• mice exhibit defective VHD rearrangement in pro-B and double positive VHD recombination and lineage specific VH to DJH recombination
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• mice exhibit a reduction in the ratio of pre-B to pro-B cells compared with wild-type mice
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• mice exhibit defective VHD rearrangement in pro-B and double positive VHD recombination and lineage specific VH to DJH recombination
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumors are more differentiated than tumors from Ightm1(Myc)Janz Tg(Emu-FGFR3)A5Wmk or Tg(Emu-FGFR3)D3Wmk heterozygotes
|
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• tumor incidence was 68% at 21 months of age
(J:96785)
• 75% of mice developed tumors at a median age of 281 days unlike wild-type mice
(J:160845)
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• most prevalent tumors were lymphoblastic B cell lymphomas with a Burkitt-like 'starry sky' morphology due to tingible body macrophages
(J:96785)
• 1/4 of lymphomas were diffuse large B cell lymphomas
(J:96785)
• lymphoblastic B-cell lymphomas contain clonal cytogenetic aberrations
(J:96785)
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• 1/5 of lymphomas were CD19+CD138+ plasmacytomas that exhibited varying degrees of differentiation, including plasmablastic, anaplastic, and plasmacytic variants
(J:96785)
• 25% of tumor exhibit plasmacytoid differentiation
(J:160845)
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• elevated apoptosis in B cells of 4- to 6-month old tumor-free mutants
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• B cells proliferated, on average, 3.8 times faster than controls and showed a 3.5-fold increase in the number of cells in S phase of the cell cycle in 4- to 6-month old, tumor-free mutants
• B splenocytes proliferated more vigorously than controls after stimulation with LPS
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• spleen was enlarged in 4- to 6-month old tumor-free mice because of progressive, follicular hyperplasia indicative of B cell accumulation
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• lymph nodes were enlarged in 4- to 6-month tumor-free mice because of progressive, follicular hyperplasia indicative of B cell accumulation
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• observed in 4- to 6-month old tumor-free mutants
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• elevated apoptosis in B cells of 4- to 6-month old tumor-free mutants
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• B cells proliferated, on average, 3.8 times faster than controls and showed a 3.5-fold increase in the number of cells in S phase of the cell cycle in 4- to 6-month old, tumor-free mutants
• B splenocytes proliferated more vigorously than controls after stimulation with LPS
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• spleen was enlarged in 4- to 6-month old tumor-free mice because of progressive, follicular hyperplasia indicative of B cell accumulation
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• elevated apoptosis in B cells of 4- to 6-month old tumor-free mutants
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• B cells proliferated, on average, 3.8 times faster than controls and showed a 3.5-fold increase in the number of cells in S phase of the cell cycle in 4- to 6-month old, tumor-free mutants
• B splenocytes proliferated more vigorously than controls after stimulation with LPS
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• spleen was enlarged in 4- to 6-month old tumor-free mice because of progressive, follicular hyperplasia indicative of B cell accumulation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Burkitt lymphoma | DOID:8584 |
OMIM:113970 |
J:96785 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Tnfsf13b treatment does not stimulate proliferation of activated B-1 cells in culture
• expression of CD21/CD35 on B-1 cells from mutants is decreased compared to wild-type
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• Tnfsf13b treatment does not stimulate proliferation of activated B-1 cells in culture
• expression of CD21/CD35 on B-1 cells from mutants is decreased compared to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduction in the number of IgMa B cells relative to IgMb B cells
|
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• reduction in the number of IgMa B cells relative to IgMb B cells
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3-fold reduction in class switch recombination in IgG1+ clones and 5-fold increase in IgE+ clones after LPS and IL4 stimulation
|
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• 3-fold reduction in class switch recombination in IgG1+ clones and 5-fold increase in IgE+ clones after LPS and IL4 stimulation
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type
(J:79556)
• in 2-4 month old mice, majority of B cells are B-2 cells, expressing high levels of IgD and B220; these cells do not express CD5 which is found on T and B-1 cells
(J:115292)
|
|
• reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type
(J:79556)
• in 2-4 month old mice, majority of B cells are B-2 cells, expressing high levels of IgD and B220; these cells do not express CD5 which is found on T and B-1 cells
(J:115292)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• few, if any, B cells formed using mutant allele
|
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• little, if any, antibody formed using the mutant allele
|
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• few, if any, B cells formed using mutant allele
|
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• little, if any, antibody formed using the mutant allele
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the allelic exclusion of B cells for IgH is lost in these mice
|
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• the allelic exclusion of B cells for IgH is lost in these mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice produce predominantly B-1 cells which express intermediate levels of CD5, low levels of B220 and IgD, and no detectable CD23
|
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• in 2-4 month old mice, B cell number in the spleen is increased 2-fold and 20-fold in peritoneal cavity compared to wild-type
|
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• mice produce predominantly B-1 cells which express intermediate levels of CD5, low levels of B220 and IgD, and no detectable CD23
|
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• in 2-4 month old mice, B cell number in the spleen is increased 2-fold and 20-fold in peritoneal cavity compared to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 3 hours after antigen injection, B cells fail to accumulate in the outer follicle instead had already arrived at the B-T boundary unlike in control cells
• however, B cells are distributed at the B-T boundary after 6 hours
|
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• 3 hours after antigen injection, B cells fail to accumulate in the outer follicle instead had already arrived at the B-T boundary unlike in control cells
• however, B cells are distributed at the B-T boundary after 6 hours
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells within in Peyer's Patches or splenic B cells stimulated in vitro can have chromosomal translocations involving chromosomes 12 and 15
• the chromosome fusions occur precisely at the two loxP sites that exist in the Igh and Myc mutant alleles
|
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• B cells within in Peyer's Patches or splenic B cells stimulated in vitro can have chromosomal translocations involving chromosomes 12 and 15
• the chromosome fusions occur precisely at the two loxP sites that exist in the Igh and Myc mutant alleles
|
|
• B cells within in Peyer's Patches or splenic B cells stimulated in vitro can have chromosomal translocations involving chromosomes 12 and 15
• the chromosome fusions occur precisely at the two loxP sites that exist in the Igh and Myc mutant alleles
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells within in Peyer's Patches or splenic B cells stimulated in vitro can have chromosomal translocations involving chromosomes 12 and 15
• the chromosome fusions occur precisely at the two loxP sites that exist in the Igh and Myc mutant alleles
|
|
• B cells within in Peyer's Patches or splenic B cells stimulated in vitro can have chromosomal translocations involving chromosomes 12 and 15
• the chromosome fusions occur precisely at the two loxP sites that exist in the Igh and Myc mutant alleles
|
|
• B cells within in Peyer's Patches or splenic B cells stimulated in vitro can have chromosomal translocations involving chromosomes 12 and 15
• the chromosome fusions occur precisely at the two loxP sites that exist in the Igh and Myc mutant alleles
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutant B cells undergo class-switching, maturation and somatic hypermutation
|
|
• double mutants show a significantly higher percentage (15.6%) of peripheral blood cells that bind hen egg lysozyme (HEL) compared to wild-type (0.016%) or Ightm1Cys knock-in mice (1.06%)
• about 70% of total B cells are HEL-binding
|
|
• double mutants show a significantly higher percentage (15.6%) of peripheral blood cells that bind hen egg lysozyme (HEL) compared to wild-type (0.016%) or Ightm1Cys knock-in mice (1.06%)
• about 70% of total B cells are HEL-binding
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lack 3-83Ig+ mature B cells, although on an H2d background some 3-83Ig+ immature B cells are detected in the bone marrow
• about and 8-fold and 15-fold increase in the frequency and absolute number of lambda expressing splenic B cells, respectively, compared to wild-type mice
• however, total B cell numbers are similar to wild-type
|
|
• lack 3-83Ig+ mature B cells, although on an H2d background some 3-83Ig+ immature B cells are detected in the bone marrow
• about and 8-fold and 15-fold increase in the frequency and absolute number of lambda expressing splenic B cells, respectively, compared to wild-type mice
• however, total B cell numbers are similar to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• about 90% of B cells are positive for the B1-8 heavy chain
|
|
• the CD43- sIgM- pre B cell compartment is virtually absent
|
|
• about 90% of B cells are positive for the B1-8 heavy chain
|
|
• the CD43- sIgM- pre B cell compartment is virtually absent
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lack 3-83Ig+ mature B cells, although on an H2d background some 3-83Ig+ immature B cells are detected in the bone marrow
|
|
• lack 3-83Ig+ mature B cells, although on an H2d background some 3-83Ig+ immature B cells are detected in the bone marrow
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slight increase in the percentage of B cells expressing IgG1
|
|
• slight increase in the percentage of B cells expressing IgG1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased percentage of B cells expressing IgG1 in the bone marrow and spleen compared to mutant mice with a wild-type Igalpha allele
|
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• increased percentage of B cells expressing IgG1 in the bone marrow and spleen compared to mutant mice with a wild-type Igalpha allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the percentage of B cells with surface IgG1 expression is doubled compared to mutant mice on a CD22-proficient background
|
|
• the percentage of B cells with surface IgG1 expression is doubled compared to mutant mice on a CD22-proficient background
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following Rbbp8 depletion using short hairpin RNA, B cell exhibit reduced frequency of recombination joins displaying extensive resection and mean number of resected nucleotides created by I-SceI compared with wild-type cells
• treatment with a small molecular inhibitor of Mre11a or Wrn produces no effect on resection of microhomology at the junctions
|
|
• following Rbbp8 depletion using short hairpin RNA, B cell exhibit reduced frequency of recombination joins displaying extensive resection and mean number of resected nucleotides created by I-SceI compared with wild-type cells
• treatment with a small molecular inhibitor of Mre11a or Wrn produces no effect on resection of microhomology at the junctions
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cell exhibit reduced frequency of recombination joins displaying extensive resection and mean number of resected nucleotides created by I-SceI compared with wild-type cells
|
|
• B cell exhibit reduced frequency of recombination joins displaying extensive resection and mean number of resected nucleotides created by I-SceI compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• innocuous transgenic BCR on Blnk null B cells leads to enhanced development of these B cells compared to Blnk homozygotes
• two populations are detected in the bone marrow consisting of IgMlo and IgMhi groups
• both populations appear to be immature B cells as they have low surface level expression of MHC-II and CD43, and high levels of CD24
• based on intensity of these surface markers, the IgMlo population is the less mature of the two
• in vitro maturation of bone marrow cells demonstrate delayed development of these IgM+ cells
• B cells in the periphery are primarily T1 stage B cells that have a short half-life
|
|
• B cells in the periphery are primarily T1 stage B cells
|
|
• B cell numbers are decreased 2- to 3- fold in the spleen
• the B cells present are primarily T1 stage B cells
|
|
• pre-B cell numbers are 2-3 fold higher in the bone marrow than in transgenic controls
|
|
• innocuous transgenic BCR on Blnk null B cells leads to enhanced development of these B cells compared to Blnk homozygotes
• two populations are detected in the bone marrow consisting of IgMlo and IgMhi groups
• both populations appear to be immature B cells as they have low surface level expression of MHC-II and CD43, and high levels of CD24
• based on intensity of these surface markers, the IgMlo population is the less mature of the two
• in vitro maturation of bone marrow cells demonstrate delayed development of these IgM+ cells
• B cells in the periphery are primarily T1 stage B cells that have a short half-life
|
|
• B cells in the periphery are primarily T1 stage B cells
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|
• B cell numbers are decreased 2- to 3- fold in the spleen
• the B cells present are primarily T1 stage B cells
|
|
• pre-B cell numbers are 2-3 fold higher in the bone marrow than in transgenic controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells have about a 2-fold increase in class switch recombination to IgG1
|
|
• B cells have about a 2-fold increase in class switch recombination to IgG1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 of 10 mice develop B cell leukemia compared to Trp53 null controls that develop T cell lymphomas
• median tumor-free survival is 143 days compared to over 365 days in transgenic controls on a wild-type Trp53 background
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 5 of 6 mice develop B cell derived leukemia compared to Trp53 null controls that develop T cell lymphomas
• median tumor-free survival is 138 days compared to 161 in transgenic controls on a wild-type Trp53 background
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice have partial block in development at pro-B cell to pre-B cells transition in bone marrow
|
|
• splenic B cell numbers were decreased by 6-fold compared to wild-type
|
| N |
• early B cell block seen in Pax5-deficient mice is rescued, as shown by presence of IgM+IgD+ mature B cells
|
|
• mice have partial block in development at pro-B cell to pre-B cells transition in bone marrow
|
|
• splenic B cell numbers were decreased by 6-fold compared to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice carrying a rearranged IgH (heavy chain) variable region from a B1-8 clone and homozygous for Xrcc6tm1Fwa exhibit small but detectable populations of peripheral kappa-light chain expressing IgM+ B cells with functional light chain rearrangements; this indicates that some light chain rearrangment can occur in Xrcc6-deficient mice and the defect in B cell differentiation is "leaky"
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|
• mice carrying a rearranged IgH (heavy chain) variable region from a B1-8 clone and homozygous for Xrcc6tm1Fwa exhibit small but detectable populations of peripheral kappa-light chain expressing IgM+ B cells with functional light chain rearrangements; this indicates that some light chain rearrangment can occur in Xrcc6-deficient mice and the defect in B cell differentiation is "leaky"
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increase in the proportion of cells that migrate towards high sphingosine 1-phosphate (S1P) concentrations
• reduction in migratory response towards S1P induced by LPS treatment is decreased compared to wild-type
• immunization with a low dose of T cell dependent antigen (NP-CG) fails to suppress responsiveness to S1P unlike in wild-type mice; however, treatment with a high concentration of antigen does reduce S1P responsiveness
|
|
• increase in the proportion of cells that migrate towards high sphingosine 1-phosphate (S1P) concentrations
• reduction in migratory response towards S1P induced by LPS treatment is decreased compared to wild-type
• immunization with a low dose of T cell dependent antigen (NP-CG) fails to suppress responsiveness to S1P unlike in wild-type mice; however, treatment with a high concentration of antigen does reduce S1P responsiveness
|
|
• increase in the proportion of cells that migrate towards high sphingosine 1-phosphate (S1P) concentrations
• reduction in migratory response towards S1P induced by LPS treatment is decreased compared to wild-type
• immunization with a low dose of T cell dependent antigen (NP-CG) fails to suppress responsiveness to S1P unlike in wild-type mice; however, treatment with a high concentration of antigen does reduce S1P responsiveness
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the percentage of B cells expressing lambda light chain is about 4 times higher than in wild-type mice
|
|
• the percentage of B cells expressing lambda light chain is about 4 times higher than in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells show defects in CSR to IgG1 and IgG3 ranging from 30%?70% of controls
|
|
• B cells show defects in CSR to IgG1 and IgG3 ranging from 30%?70% of controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the frequency of B220+ B cells in the periphery is 10.1% compared to 24.7% in mice with just one Igk knock-in allele
|
|
• the frequency of B220+ B cells in the periphery is 10.1% compared to 24.7% in mice with just one Igk knock-in allele
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• B cells exhibit normal resection and junctional microhomology
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit increased premature lethality compared with Ightm1Janz heterozygotes
|
|
• lymphomagenesis is accelerated compared to in Ightm1Janz heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cell surface IgM levels are somewhat lower in B220+ and E4+ cells
• two cell populations, one in which surface IgD levels are normal, another in which they are substantially reduced
|
|
• modestly reduced
|
|
• cell surface IgM levels are somewhat lower in B220+ and E4+ cells
• two cell populations, one in which surface IgD levels are normal, another in which they are substantially reduced
|
|
• modestly reduced
|
|
• cell surface IgD levels as in the spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cell surface IgM levels are generally lower and particularly lower in E4+ cells
• cell surface IgD levels are normal except in E4+ cells where it is dramatically reduced
• lambda-L chain levels were elevated 3X generally but were undetectable in E4+ B cells
|
|
• B cell development was normal in bone marrow
• splenic B cells with a follicular phenotype and are E4+
• B cells do not express endogenous mu-chain
|
|
• B cell area decreased in size
|
|
• cell surface IgM levels are generally lower and particularly lower in E4+ cells
• cell surface IgD levels are normal except in E4+ cells where it is dramatically reduced
• lambda-L chain levels were elevated 3X generally but were undetectable in E4+ B cells
|
|
• B cell development was normal in bone marrow
• splenic B cells with a follicular phenotype and are E4+
• B cells do not express endogenous mu-chain
|
|
• B cell area decreased in size
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• when germinal center B cells from these mice are transferred to wild-type recipients that are then immunized with duck egg lysozyme conjugated with ovalbumin, the Ightm1Cys, Tg(Igk)5Cys GC B cells undergo apparently normal class switching, maturation and somatic hypermutation
• class switching to IgG2a and IgG2b is observed by day 7 after immunization
• an increased number of somatic hypermutations are detected as the germinal center response progressed as is selection for particular mutations by day 14
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumors are less differentiated than tumors from Ightm1(Myc)Janz heterozygotes
|
|
• 98% of mice developed tumors at a median age of 156 days unlike wild-type mice
|
|
• 1 tumor exhibits plasmacytoid differentiation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple myeloma | DOID:9538 |
OMIM:254500 |
J:160845 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumors are less differentiated than tumors from Ightm1(Myc)Janz heterozygotes
|
|
• 98% of mice developed tumors at a median age of 156 days unlike wild-type mice
|
|
• 1 tumor exhibits plasmacytoid differentiation
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple myeloma | DOID:9538 |
OMIM:254500 |
J:160845 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cells do not develop past this stage
|
|
• B cells do not develop past this stage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• four fold reduction of mature B cells in the spleen
|
|
• four fold reduction of mature B cells in the spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 40-60% of B cells in the spleen produce immunoglobulins that bind hen egg lysozyme antigen (HEL) with high affinity
|
|
• the splenic B cells that bind HEL antigen are immature as indicated by the IgMhi IgDhi surface markers
|
|
• all of the B cells found in the peritoneal cavity that bind HEL antigen are of the B-2 lineage as determined by B220hi CD5lowexpression
|
|
• there are low levels of anti-HEL IgA in the sera of unimmunized mice
|
|
• there are low levels of anti-HEL IgG1 in the sera of unimmunized mice
|
|
• there are low levels of anti-HEL IgG2a in the sera of unimmunized mice
|
|
• there are low levels of anti-HEL IgG2b in the sera of unimmunized mice
|
|
• there are low levels of anti-HEL IgG3 in the sera of unimmunized mice
|
|
• there are high levels of anti-HEL IgM in the sera of unimmunized mice
|
|
• 40-60% of B cells in the spleen produce immunoglobulins that bind hen egg lysozyme antigen (HEL) with high affinity
|
|
• the splenic B cells that bind HEL antigen are immature as indicated by the IgMhi IgDhi surface markers
|
|
• all of the B cells found in the peritoneal cavity that bind HEL antigen are of the B-2 lineage as determined by B220hi CD5lowexpression
|
|
• there are low levels of anti-HEL IgA in the sera of unimmunized mice
|
|
• there are low levels of anti-HEL IgG1 in the sera of unimmunized mice
|
|
• there are low levels of anti-HEL IgG2a in the sera of unimmunized mice
|
|
• there are low levels of anti-HEL IgG2b in the sera of unimmunized mice
|
|
• there are low levels of anti-HEL IgG3 in the sera of unimmunized mice
|
|
• there are high levels of anti-HEL IgM in the sera of unimmunized mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a 2-fold reduction in the number of HEL-specific B cells found in the spleen
|
|
• HEL-specific B cells in the spleen have mostly have an immature phenotype
|
|
• few HEL-specific B cells in the spleen are found in the follicular region or have surface markers indicative of follicular B cells
|
|
• very few HEL-specific B cells in the spleen are found in the marginal zone or have surface markers indicative of the marginal zone phenotype
|
|
• there is a 2-fold reduction in the number of HEL-specific B cells found in the spleen
|
|
• HEL-specific B cells in the spleen have mostly have an immature phenotype
|
|
• few HEL-specific B cells in the spleen are found in the follicular region or have surface markers indicative of follicular B cells
|
|
• very few HEL-specific B cells in the spleen are found in the marginal zone or have surface markers indicative of the marginal zone phenotype
|
|
• 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
• these anergic B cells have a short half-life of less than three days
• however, these anergic B cells can proliferate in response to BCR-independent activation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following Rbbp8 depletion using short hairpin RNA, B cell exhibit reduced frequency of recombination joins displaying extensive resection and mean number of resected nucleotides created by I-SceI compared with wild-type cells
|
|
• following Rbbp8 depletion using short hairpin RNA, B cell exhibit reduced frequency of recombination joins displaying extensive resection and mean number of resected nucleotides created by I-SceI compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• activated B cells transfected with yeast-derived I-SceI endonuclease have a high incidence of chromosomal translocations involving chromosomes 12 and 15
• chromosome fusions occur within 2.2 kb of the I-SceI recognition sites that are present in the Myc and Igh mutant alleles
• out of 21 translocation junctions, 19 involved 1-7 bps of microhomology (average microhomology of 2.9 bps) and two included insertions
• translocation rates are similar when B cells are transfected with Aicda, cre, or SceI genes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B cell exhibit reduced frequency of recombination joins displaying extensive resection and mean number of resected nucleotides created by I-SceI compared with wild-type cells
|
|
• B cell exhibit reduced frequency of recombination joins displaying extensive resection and mean number of resected nucleotides created by I-SceI compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice have 2-fold more splenic B cells than Ightm1Kplm mutants and 8-fold more cells than Tg(Igk-V4CH27)1-2Shc or Ightm4Cgn, Tg(Igk-V4CH27)1-2Shc mutants
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|
• mice have 2-fold more splenic B cells than Ightm1Kplm mutants and 8-fold more cells than Tg(Igk-V4CH27)1-2Shc or Ightm4Cgn, Tg(Igk-V4CH27)1-2Shc mutants
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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 03/18/2025 MGI 6.24 |
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