JAX Mouse Strain Datasheet - 005306

NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ

Stock No:: 005306 |; NOD.mIgM

Cryo Recovery

Overview

Also Known As: NOD.mIgM

A fraction of these transgenic mice show increased insulitis, and diabetes incidence is partially restored in females.

Donating Investigator

F. S. Wong, University of Bristol

Genetic overview

Genetic Background	Generation
NOD/Caj

Ighm^tm1Cgn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ighm	immunoglobulin heavy constant mu

Allele Type
Transgenic (Inserted expressed sequence)

Research Applications

Diabetes and Obesity Research
Immunology, Inflammation and Autoimmunity Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

Transgenic mice carrying the Ighm^tm1Cgn allele are viable, fertile, and normal in size and restores the B220+ B-cells to normal. The number of B-cells is normal and the ratio of CD4 to CD8 is normal. Although only a fraction of the transgenic mice have an increased amount of insulitis, it is more severe, especially in males. Diabetes incidence is partially restored in NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/Fsw with approximately, 11% females and 0% males becoming diabetic by 50 weeks of age compared to approximately 2% Ighm^tm1Cgn female controls and 0% Ighm^tm1Cgn male controls by 50 weeks of age or 90% female NOD controls and 70% male NOD controls by 30 weeks of age. T- cell depleted spleen cells from Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk mice stimulated with lipopolysaccharide (LPS) respond normally. NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m )2Mjsk/Fsw like NOD.129S2(B6)-Ighm^tm1Cgn generate low T-cell responses to GAD and insulin.

This model is useful for separating the role of B-cells in antigen presentation from antibody production involved in diabetes development.

Development

The transgenic construct Tg(Igh-VB1-8/Igh-6m)1Mjsk that encodes a membrane bound, but not a secreted, immunoglobulin mu heavy chain, was injected into NOD/Caj zygotes. Founders were backcrossed to NOD/Caj. An outcross-intercross strategy was employed to introduce an inactivated Ighm allele from NOD.129S2(B6)-Ighm^tm1Cgn. In 2005, the Type 1 Diabetes Resource received NOD/Caj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ at generation N12F3.

Expression Data

Expressed Gene	Ighm, immunoglobulin heavy constant mu, mouse, laboratory
Site of Expression

Control Suggestions

Homozygote for Ighm^tm1Cgn, Wildtype for Tg(Igh-VB1-8/Igh-6m)1Mjsk
005309 NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6)2Mjsk/FswJ

Additional Information

Considerations for Choosing Controls

Selected References

Wong FS; Wen L; Tang M; Ramanathan M; Visintin I; Daugherty J; Hannum LG; Janeway CA Jr; Shlomchik MJ. 2004. Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes 53(10):2581-7. PubMed: 15448087 MGI: J:93190

View All References

Genetics

Ighm^tm1Cgn

Allele Symbol: Ighm^tm1Cgn

Allele Name	targeted mutation 1, University of Cologne
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	B cell^-; BCKO; BCR-; BKO; Cmu ^-; Ig- muMT; Ig^-; IgH-; IgH^muMT; Igh-6-; Igh-6^null; Igh-6^tm1Cgn; Igh-6tm1CgnmuMT⁰; Ighm^-; Igmu^null; mu-MT^-; muIgKO; muMT; muMt-; mum^-
Gene Symbol and Name	Ighm, immunoglobulin heavy constant mu
Gene Synonym(s)	AI326478; BCR; Ig mu; IgM; Igh-6; Igh-M; Igh-M; Igh6; expressed sequence AI326478; immunoglobulin heavy chain 6 (heavy chain of IgM); immunoglobulin heavy chain mu; muH; muMT
Strain of Origin	129S2/SvPas
Chromosome	12
Molecular Note	A neomycin resistance cassette disrupted one of the membrane exons of the gene encoding immunoglobulin heavy chain of the class mu (IgM).
Mutations Made By	Daisuke Kitamura, University of Cologne

Tg(Igh-VB1-8/Igh-6m)1Mjsk

Allele Symbol: Tg(Igh-VB1-8/Igh-6m)1Mjsk

Allele Name	transgene insertion 1, Mark J Shlomchik
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	Tg(Igh-VB1-8/Igh-6)1Mjsk; mIg
Gene Symbol and Name	Tg(Igh-VB1-8/Igh-6m)1Mjsk, transgene insertion 1, Mark J Shlomchik
Gene Synonym(s)	Tg(Igh-VB1-8/Igh-6)1Mjsk; Tg(Igh-VB1-8/Igh-6)1Mjsk; mIg
Promoter	Igh-V, immunoglobulin heavy chain variable region, mouse, laboratory
Expressed Gene	Ighm, immunoglobulin heavy constant mu, mouse, laboratory
Strain of Origin	NOD/Caj
Chromosome	UN
Molecular Note	The transgene encodes a membrane-bound, but not a secreted, immunoglobulin mu heavy chain. The variable region of the transgene comprises the VDJ moiety from the functionally rearranged Igh gene of the C57BL/6-derived B1-8 hybridoma, containing the V-region segment Vh186.2 and recognizing the hapten (4-hydroxy-3-nitrophenyl)acetyl. This is followed by a J-C intron fragment containing the Igh intronic enhancer and an Igh-6 constant region gene (of haplotype a) from which the exon encoding the secreted form of Igmu and its associated polyadenylation signal have been deleted.
Mutations Made By	Mark Shlomchik, Yale School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
- Type 1 Diabetes (IDDM)
- Type 1 Diabetes (IDDM) Analysis Strains
  - NOD Congenics with Mutations Affecting Immunocompetence
  - NOD Transgenics
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - B cell deficiency
  - Type 1 Diabetes
- Immunodeficiency
  - B cell defects

Genotype: Ighm^tm1Cgn related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B cell deficiency
Research Tools
- Cancer Research
  - B cell deficiency
- Immunology, Inflammation and Autoimmunity Research
  - B cell deficiency

Mammalian Phenotype Terms by Genotype

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/?
NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ

immune system phenotype

increased susceptibility to autoimmune diabetes
- female Igh-6-deficient transgenic mice show a 7-fold increase in the incidence of (blood glucose >250 mg/dl) diabetes compared with nontransgenic littermates

References

Wong FS; Wen L; Tang M; Ramanathan M; Visintin I; Daugherty J; Hannum LG; Janeway CA Jr; Shlomchik MJ. 2004. Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes 53(10):2581-7. PubMed: 15448087 MGI: J:93190

Additional - Ighm^tm1Cgn related

Abraham D; Leon O; Schnyder-Candrian S; Wang CC; Galioto AM; Kerepesi LA; Lee JJ; Lustigman S. 2004. Immunoglobulin E and eosinophil-dependent protective immunity to larval Onchocerca volvulus in mice immunized with irradiated larvae. Infect Immun 72(2):810-7. PubMed: 14742524 MGI: J:87861
Akashi T; Nagafuchi S; Anzai K; Kitamura D; Wang J; Taniuchi I; Niho Y; Watanabe T. 1998. Proliferation of CD3+ B220- single-positive normal T cells was suppressed in B-cell-deficient lpr mice. Immunology 93(2):238-48. PubMed: 9616374 MGI: J:45808
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Allen HL; Deepe GS Jr. 2006. B cells and CD4-CD8- T cells are key regulators of the severity of reactivation histoplasmosis. J Immunol 177(3):1763-71. PubMed: 16849486 MGI: J:138028
Alpan O; Rudomen G; Matzinger P. 2001. The role of dendritic cells, B cells, and M cells in gut-oriented immune responses. J Immunol 166(8):4843-52. PubMed: 11290760 MGI: J:68620
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Yan J; Harvey BP; Gee RJ; Shlomchik MJ; Mamula MJ. 2006. B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated autoantigen presentation. J Immunol 177(7):4481-7. PubMed: 16982884 MGI: J:139321
Yu S; Maiti PK; Dyson M; Jain R; Braley-Mullen H. 2006. B cell-deficient NOD.H-2h4 mice have CD4+CD25+ T regulatory cells that inhibit the development of spontaneous autoimmune thyroiditis. J Exp Med 203(2):349-58. PubMed: 16446379 MGI: J:118956

Also Known As: NOD.mIgM

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Ighmtm1Cgn

Allele Symbol: Ighmtm1Cgn

Tg(Igh-VB1-8/Igh-6m)1Mjsk

Allele Symbol: Tg(Igh-VB1-8/Igh-6m)1Mjsk

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Ighmtm1Cgn related

Mammalian Phenotype Terms by Genotype

Genotype: Ighmtm1Cgn/Ighmtm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/?NODCaj.Cg-Ighmtm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ

immune system phenotype

References

Additional - Ighmtm1Cgn related

Additional - Tg(Igh-VB1-8/Igh-6m)1Mjsk related

Genotyping Protocols

Dietary Information

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

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Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

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Ighm^tm1Cgn

Allele Symbol: Ighm^tm1Cgn

Genotype: Ighm^tm1Cgn related

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/?
NODCaj.Cg-Ighm^tm1Cgn Tg(Igh-VB1-8/Igh-6m)1Mjsk/FswJ

Additional - Ighm^tm1Cgn related