Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
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mortality/aging
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• following administration of 15 ug cholera toxin
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immune system
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• absent class switching in B cells
(J:73659)
• class switching recombination (CSR)-induced Smu internal deletion is impaired
(J:120658)
• B cells cultured with LPS and IL-4 fail to switch immunoglobulin expression to IgG1
(J:141427)
• similar defects in IgG3 switching are also observed
(J:141427)
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• mice exhibit an increase in somatic hypermutation rates compared to in wild-type mice
(J:136224)
• the somatic mutation rates of the upstream region of the S-mu switch is severely reduced
(J:141427)
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• in Peyer's patches and spleen
• in the lamina propria and Peyer's patches
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• levels are less than one tenth of those in controls
(J:73659)
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• levels are less than one tenth of those in controls
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• 2-3 fold elevation in IgM level
(J:73659)
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• following administration of 15 ug cholera toxin
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hematopoietic system
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• absent class switching in B cells
(J:73659)
• class switching recombination (CSR)-induced Smu internal deletion is impaired
(J:120658)
• B cells cultured with LPS and IL-4 fail to switch immunoglobulin expression to IgG1
(J:141427)
• similar defects in IgG3 switching are also observed
(J:141427)
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• mice exhibit an increase in somatic hypermutation rates compared to in wild-type mice
(J:136224)
• the somatic mutation rates of the upstream region of the S-mu switch is severely reduced
(J:141427)
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• in Peyer's patches and spleen
• in the lamina propria and Peyer's patches
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• levels are less than one tenth of those in controls
(J:73659)
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• levels are less than one tenth of those in controls
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• 2-3 fold elevation in IgM level
(J:73659)
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Allelic
Composition |
Aicdatm1Hon/Aicda+
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Genetic
Background |
involves: C57BL/6 * CBA |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
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immune system
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N |
• mice exhibit normal somatic hypermutation rates
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• class switching is impaired compared to in wild-type mice
(J:136224)
• B cells show 80% the level of class switch recombination (CSR) to IgG1 that occurs with wild-type controls when cultured in the presence of LPS and IL-4
(J:141427)
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• somatic hypermutation by germinal center B cells is 75% of what occurs in wild-type
• somatic hypermutation by Peyer's patch B cells is 40% of what occurs in wild-type
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hematopoietic system
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• class switching is impaired compared to in wild-type mice
(J:136224)
• B cells show 80% the level of class switch recombination (CSR) to IgG1 that occurs with wild-type controls when cultured in the presence of LPS and IL-4
(J:141427)
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• somatic hypermutation by germinal center B cells is 75% of what occurs in wild-type
• somatic hypermutation by Peyer's patch B cells is 40% of what occurs in wild-type
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1.1Fwa mutation
(0 available);
any
Aicda mutation
(55 available)
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
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immune system
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N |
• mice exhibit normal numbers of splenic B and T cells and response to activation
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• severely decreased class switch recombination to IgG1 and IgG3
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hematopoietic system
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• severely decreased class switch recombination to IgG1 and IgG3
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
Aicdatm4Mnz mutation
(0 available);
any
Aicda mutation
(55 available)
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immune system
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• B cells show 45% the level of class switch recombination to IgG1 that occurs with wild-type controls when cultured in the presence of LPS and IL-4
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• the somatic mutation rate of the upstream region of the S-mu switch repeats is 85% the rate that occurs in stimulated wild-type B cells
• somatic hypermutation by germinal center and Peyer's patch B cells does not exceed basal mutation rates
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hematopoietic system
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• B cells show 45% the level of class switch recombination to IgG1 that occurs with wild-type controls when cultured in the presence of LPS and IL-4
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• the somatic mutation rate of the upstream region of the S-mu switch repeats is 85% the rate that occurs in stimulated wild-type B cells
• somatic hypermutation by germinal center and Peyer's patch B cells does not exceed basal mutation rates
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cellular
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• B cells exhibit a 3- to 6-fold increase in reciprocal chromosome translocations between Igh and Myc compared to in Aicdatm1Hon heterozygotes
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immune system
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N |
• mice exhibit normal B cell development in the bone marrow, peripheral B cell numbers in the spleen, serum immunoglobulin isotypes, class switching, and somatic hypermutation rates
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
Aicdatm3Mnz mutation
(0 available);
any
Aicda mutation
(55 available)
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immune system
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• B cells show 4% the level of class switch recombination (CSR) to IgG1 that occurs with wild-type controls when cultured in the presence of LPS and IL-4
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• the somatic mutation rate of the upstream region of the S-mu switch repeats is 25% the rate that occurs in stimulated wild-type B cells
• somatic hypermutation by germinal center and Peyer's patch B cells does not exceed basal mutation rates
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hematopoietic system
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• B cells show 4% the level of class switch recombination (CSR) to IgG1 that occurs with wild-type controls when cultured in the presence of LPS and IL-4
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• the somatic mutation rate of the upstream region of the S-mu switch repeats is 25% the rate that occurs in stimulated wild-type B cells
• somatic hypermutation by germinal center and Peyer's patch B cells does not exceed basal mutation rates
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hematopoietic system
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• I-SceI mediated class switch recombination in LPS- and IL4-stimulated B cells is decreased compared to similarly treated Aicdatm1Hon/Aicdatm1Hon Ightm3Mnz/Ightm4.1Mnz B cells
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immune system
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• I-SceI mediated class switch recombination in LPS- and IL4-stimulated B cells is decreased compared to similarly treated Aicdatm1Hon/Aicdatm1Hon Ightm3Mnz/Ightm4.1Mnz B cells
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| 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)
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cellular
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• 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
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immune system
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• 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
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hematopoietic system
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• 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
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immune system
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• 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
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hematopoietic system
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
Ighmtm1.1(IGH-2)Cog mutation
(0 available);
any
Ighm mutation
(55 available)
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immune system
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• mIgA1+ cells compete poorly for entry into mucosa-associated lymphoid tissues compared with wild-type cells
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hematopoietic system
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• mIgA1+ cells compete poorly for entry into mucosa-associated lymphoid tissues compared with wild-type cells
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
Bcl6tm1.1Jwan mutation
(0 available);
any
Bcl6 mutation
(55 available)
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hematopoietic system
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• mice fail to exhibit mutations in the knock-in allele
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immune system
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• mice fail to exhibit mutations in the knock-in allele
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immune system
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N |
• B cells exhibit normal resection and junctional microhomology
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
Ightm4.1Mnz mutation
(0 available);
any
Igh mutation
(43 available)
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immune system
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• 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
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hematopoietic system
|
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
Tg(Igkv3-5*-MYC)#Plbe mutation
(0 available)
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immune system
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N |
• unlike Tg(Igkv3-5*-Myc)#Plbe mice, no spikes in monoclonal antibodies (M-spikes) are observed
• mice exhibit fewer plasma cells in the bone marrow compared with Tg(Igkv3-5*-Myc)#Plbe mice
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cellular
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1Hon mutation
(7 available);
any
Aicda mutation
(55 available)
Exo1tm1Wed mutation
(0 available);
any
Exo1 mutation
(45 available)
Ightm4.1Mnz mutation
(0 available);
any
Igh mutation
(43 available)
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immune system
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• 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
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hematopoietic system
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• 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
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Analysis Tools