Description

Strain Information

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-6^tm1Che allele are viable, fertile and exhibit no apparent defects. While membrane expressed Igh-6^tm1Che is unhindered, these mice are unable to produce the secreted form of Igh-6^tm1Che. 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 Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Igh-6

002249	B10.129S2(B6)-Igh-6tm1Cgn/J
002288	B6.129S2-Igh-6tm1Cgn/J
004349	C.129S2-Igh-6tm1Cgn/J
002030	C57BL/6-Tg(Igh-3/Igh-6VD93)1241Ust/J
005020	NOD-Tg(Igh-6/Igh-V281)3Jwt/JwtJ
004639	NOD.129S2(B6)-Igh-6tm1Cgn/DoiJ
003903	NOD.129S2-Igh-6tm1Cgn/Dvs
006608	NOD.Cg-Igh-6tm1Cgn Tg(IghelMD4)4Ccg/DvsJ
005019	NOD.Cg-Tg(Igh-6/Igh-V125)2Jwt/JwtJ
007769	NOD.FVB-Tg(Igh-6-Cd80)1Gjf/JbsJ
005309	NODCaj.Cg-Igh-6tm1Cgn Tg(Igh-VB1-8/Igh-6)2Mjsk/FswJ
005306	NODCaj.Cg-Igh-6tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ

View Strains carrying other alleles of Igh-6     (12 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Igh-6^tm1Che/Igh-6^tm1Che

        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-6^tm1Che related

Immunology and Inflammation Research
Immunodeficiency (B cell deficiency)

Research Tools
Cancer Research (B cell deficiency)
Immunology and Inflammation Research (B cell deficiency)

Genes & Alleles

Gene & Allele Information

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

Genotyping Information

Genotyping Protocols

Igh-6^tm1Che, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Additional References

Igh-6^tm1Che related

Alugupalli 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]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	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.

General Terms and Conditions

See Terms of Use

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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phone:	207-288-6470
fax:	207-288-6655

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