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Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Jianzhu Chen, MIT Center for Cancer Research Description
Mice homozygous for the Igh-6tm1Che allele are viable, fertile and exhibit no apparent defects. While membrane expressed Igh-6tm1Che is unhindered, these mice are unable to produce the secreted form of Igh-6tm1Che. Increases in some classes of serum Ig is noted in young animals (IgA, IgG2a and IgG3), but these differences are largely absent in the adult animals. The IgG1 antibody response to suboptimal doses of a T cell-dependent antigen is impaired. Conversely, the IgG2a antibody response to a T cell-independent antigen appears augmented. An approximately three-fold increase in B-1 lymphocytes is noted in the spleen and peritoneum.
| Control | ||
|---|---|---|
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Igh-6
View Strains carrying other alleles of Igh-6 (12 strains)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Igh-6tm1Che/Igh-6tm1Che
involves: 129S4/SvJae * C57BL/6
- immune system phenotype
- abnormal immune system physiology (MGI Ref ID J:47425)
- germinal center reactions are impaired when 1 ug of NP-KLH antigen is used for immunization
- antibody affinity maturation is compromised in response to suboptimal doses of antigen (NP5-BSA or NP15-BSA)
- abnormal B cell physiology (MGI Ref ID J:47425)
- decreased IgG1 level (MGI Ref ID J:47425)
- IgG1 levels after immunization with a suboptimal dose (<10 ug) of T cell-dependent antigen NP-KLH >100-fold lower in mutants
- decreased IgG2b level (MGI Ref ID J:47425)
- treatment with the T cell independent antigen NP-Ficoll reduced IgG2b levels after immunization
- decreased IgM level (MGI Ref ID J:47425)
- IgM levels in serum are ~0.1 ug/ml compared to ~250 ug/ml in serum of wild-type controls; levels do not increase in mice up to 1 year in age
- increased IgA level (MGI Ref ID J:47425)
- elevated in serum of mutants at young ages
- increased IgG2a level (MGI Ref ID J:47425)
- elevated in serum of mutants at 4 weeks, but difference disappears as mice mature
- treatment with the T cell independent antigen NP-Ficoll results in 3-4-fold increase in IgG2a at 7 and 14 days after immunization
- increased IgG3 level (MGI Ref ID J:47425)
- elevated in serum of mutants at 4 weeks, but difference disappears as mice mature
- abnormal follicular dendritic cell antigen presentation (MGI Ref ID J:47425)
- antigen trapping on follicular dendritic cells (FDCs) in spleen germinal centers is impaired when 10 ug of NP-KLH antigen is used for immunization; no antigen trapping is detected on FDCs 12 days after immunization, even though titers of NP-specific IgG antibodies are comparable to wild-type
- abnormal humoral immune response (MGI Ref ID J:47425)
- treatment with the T cell independent antigen NP-Ficoll results in 3-4-fold increase in IgG2a at 7 and 14 days after immunization
- IgG responses to T cell-dependent antigen NP-KLH are impaired at suboptimal antigen doses; at a suboptimal dose 7 days after immunization, IgG antibody levels are ~25-fold lower for primary and secondary responses relative to heterozygous controls
- decreased IgG1 level (MGI Ref ID J:47425)
- IgG1 levels after immunization with a suboptimal dose (<10 ug) of T cell-dependent antigen NP-KLH >100-fold lower in mutants
- decreased IgG2b level (MGI Ref ID J:47425)
- treatment with the T cell independent antigen NP-Ficoll reduced IgG2b levels after immunization
- decreased IgM level (MGI Ref ID J:47425)
- IgM levels in serum are ~0.1 ug/ml compared to ~250 ug/ml in serum of wild-type controls; levels do not increase in mice up to 1 year in age
- increased IgA level (MGI Ref ID J:47425)
- elevated in serum of mutants at young ages
- increased IgG2a level (MGI Ref ID J:47425)
- elevated in serum of mutants at 4 weeks, but difference disappears as mice mature
- treatment with the T cell independent antigen NP-Ficoll results in 3-4-fold increase in IgG2a at 7 and 14 days after immunization
- increased IgG3 level (MGI Ref ID J:47425)
- elevated in serum of mutants at 4 weeks, but difference disappears as mice mature
- abnormal spleen morphology (MGI Ref ID J:125338)
- abnormal spleen white pulp morphology (MGI Ref ID J:125338)
- abnormal metallophillic macrophage morphology (MGI Ref ID J:125338)
- after LPS challenge, marginal zone metallophilic -2+ (MOMA-2+) macrophages of the T and B cell zone fail to establish a ring of complement 3 (C3)-producing macrophages in the outer B cell zone close to the marginal zone
- abnormal spleen B cell follicle morphology (MGI Ref ID J:125338)
- 72 hours after LPS challenge, spleen white pulp area continues to deteriorate; B cell follicles dissolve
- abnormal spleen germinal center morphology (MGI Ref ID J:47425)
- 7 days after secondary immunization with suboptimal dose of T cell-dependent antigen NP-KLH, number and size of germinal centers in mutant spleens are reduced compared to controls; number is reduced ~4fold, but numbers are normal in mice immunized with 10 or 100 ug of antigen
- germinal center reactions are also impaired when 1 ug of NP-KLH antigen is used for immunization
- abnormal spleen marginal zone morphology (MGI Ref ID J:125338)
- after 72 hours of LPS treatment, marginal zone is no longer structured; rings of 2F8+, ER-TR9+, and MOMA-1+ macrophages are not detectable
- abnormal spleen periarteriolar lymphoid sheath morphology (MGI Ref ID J:125338)
- T cell zone shows severe destruction with disorganized B and T cells 72 hours after LPS treatment
- increased B-1 B cell number (MGI Ref ID J:47425)
- in spleen of mutants, a 2.6-fold increase in B-1 cells is detected
- in peritoneum, B-1 B cell numbers are elevated ~3-fold at 4 weeks of age through 12 months
- hematopoietic system phenotype
- abnormal spleen morphology (MGI Ref ID J:125338)
- abnormal spleen white pulp morphology (MGI Ref ID J:125338)
- abnormal metallophillic macrophage morphology (MGI Ref ID J:125338)
- after LPS challenge, marginal zone metallophilic -2+ (MOMA-2+) macrophages of the T and B cell zone fail to establish a ring of complement 3 (C3)-producing macrophages in the outer B cell zone close to the marginal zone
- abnormal spleen B cell follicle morphology (MGI Ref ID J:125338)
- 72 hours after LPS challenge, spleen white pulp area continues to deteriorate; B cell follicles dissolve
- abnormal spleen germinal center morphology (MGI Ref ID J:47425)
- 7 days after secondary immunization with suboptimal dose of T cell-dependent antigen NP-KLH, number and size of germinal centers in mutant spleens are reduced compared to controls; number is reduced ~4fold, but numbers are normal in mice immunized with 10 or 100 ug of antigen
- germinal center reactions are also impaired when 1 ug of NP-KLH antigen is used for immunization
- abnormal spleen marginal zone morphology (MGI Ref ID J:125338)
- after 72 hours of LPS treatment, marginal zone is no longer structured; rings of 2F8+, ER-TR9+, and MOMA-1+ macrophages are not detectable
- abnormal spleen periarteriolar lymphoid sheath morphology (MGI Ref ID J:125338)
- T cell zone shows severe destruction with disorganized B and T cells 72 hours after LPS treatment
- increased B-1 B cell number (MGI Ref ID J:47425)
- in spleen of mutants, a 2.6-fold increase in B-1 cells is detected
- in peritoneum, B-1 B cell numbers are elevated ~3-fold at 4 weeks of age through 12 months
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Igh-6tm1Che related
Immunology and Inflammation Research
Immunodeficiency (B cell deficiency)
Research Tools
Cancer Research (B cell deficiency)
Immunology and Inflammation Research (B cell deficiency)
| Allele Symbol | Igh-6tm1Che | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Jianzhu Chen | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | muS-; | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/SvJae | ||
| Gene Symbol and Name | Igh-6, immunoglobulin heavy chain 6 (heavy chain of IgM) | ||
| Chromosome | 12 | ||
| Gene Common Name(s) | AI326478; BCR; DKFZp686I15196; DKFZp686I15212; FLJ00385; Ig mu; IgM; Igh-M; Igh6; MGC104996; MGC52291; MU; VH; expressed sequence AI326478; immunoglobulin heavy chain mu; muH; muMT; | ||
| Molecular Note | A targeting vector was constructed in which the exon encoding the secreted form of the immunoglobulin mu (IgM) heavy chain and its three downstream poly(A) sites were replaced by a cDNA fragment encoding the constant region mu4 exon and the exon encodingthe membrane-bound form of IgM. The resultant homozygous mutant mice had B cells that did not secrete IgM, but did express membrane-bound IgM. [MGI Ref ID J:47425] | ||
Genotyping Protocols
Igh-6tm1Che, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Boes M; Esau C; Fischer MB; Schmidt T; Carroll M; Chen J. 1998. Enhanced B-1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM. J Immunol 160(10):4776-87. [PubMed: 9590224] [MGI Ref ID J:47425]
Igh-6tm1Che relatedAlugupalli KR; Gerstein RM; Chen J; Szomolanyi-Tsuda E; Woodland RT; Leong JM. 2003. The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes. J Immunol 170(7):3819-27. [PubMed: 12646649] [MGI Ref ID J:125443]
Boes M; Prodeus AP; Schmidt T; Carroll MC; Chen J. 1998. A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection. J Exp Med 188(12):2381-6. [PubMed: 9858525] [MGI Ref ID J:111336]
Carragher DM; Kaminski DA; Moquin A; Hartson L; Randall TD. 2008. A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J Immunol 181(6):4168-76. [PubMed: 18768874] [MGI Ref ID J:139087]
Colombo MJ; Alugupalli KR. 2008. Complement Factor H-Binding Protein, a Putative Virulence Determinant of Borrelia hermsii, Is an Antigenic Target for Protective B1b Lymphocytes. J Immunol 180(7):4858-64. [PubMed: 18354209] [MGI Ref ID J:133379]
Fischer MB; Ruger B; Vaculik C; Becherer A; Wadsak W; Yanagida G; Losert UM; Chen J; Carroll MC; Eibl MM. 2007. The presence of MOMA-2(+) macrophages in the outer B cell zone and protection of the splenic micro-architecture from LPS-induced destruction depend on secreted IgM. Eur J Immunol 37(10):2825-33. [PubMed: 17899553] [MGI Ref ID J:125338]
Langford TD; Housley MP; Boes M; Chen J; Kagnoff MF; Gillin FD; Eckmann L. 2002. Central importance of immunoglobulin A in host defense against Giardia spp. Infect Immun 70(1):11-8. [PubMed: 11748158] [MGI Ref ID J:74568]
Maaser C; Housley MP; Iimura M; Smith JR; Vallance BA; Finlay BB; Schreiber JR; Varki NM; Kagnoff MF; Eckmann L. 2004. Clearance of Citrobacter rodentium requires B cells but not secretory immunoglobulin A (IgA) or IgM antibodies. Infect Immun 72(6):3315-24. [PubMed: 15155635] [MGI Ref ID J:90245]
Rajan B; Ramalingam T; Rajan TV. 2005. Critical role for IgM in host protection in experimental filarial infection. J Immunol 175(3):1827-33. [PubMed: 16034125] [MGI Ref ID J:107274]
Szczepanik M; Akahira-Azuma M; Bryniarski K; Tsuji RF; Kawikova I; Ptak W; Kiener C; Campos RA; Askenase PW. 2003. B-1 B cells mediate required early T cell recruitment to elicit protein-induced delayed-type hypersensitivity. J Immunol 171(11):6225-35. [PubMed: 14634139] [MGI Ref ID J:118473]
Tirosh B; Iwakoshi NN; Glimcher LH; Ploegh HL. 2005. XBP-1 specifically promotes IgM synthesis and secretion, but is dispensable for degradation of glycoproteins in primary B cells. J Exp Med 202(4):505-16. [PubMed: 16103408] [MGI Ref ID J:100496]
Youd ME; Luus L; Corley RB. 2004. IgM monomers accelerate disease manifestations in autoimmune-prone Fas-deficient mice. J Autoimmun 23(4):333-43. [PubMed: 15571927] [MGI Ref ID J:94230]
Currently there no information available for this strain. This may be due to the supply level of this strain.
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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