JAX Mouse Strain Datasheet - 006608

NOD.Cg-Ighm^tm1Cgn Tg(IghelMD4)4Ccg/DvsJ

Stock No:: 006608 |; NOD.IgHEL,Igh-/-

Cryo Recovery

Overview

Also Known As: NOD.IgHEL,Igh-/-, NOD.IgHEL.Igμ^null, NOD.IgHEL.Igu

Mice of this strain do not express endogenous IgM, and all B lymphocytes express Ig molecules specific for hen egg lyzozyme (HEL). This strain may be used to study defects in B-cell selection as it relates to Type 1 Diabetes.

Donating Investigator

Dr. David Serreze, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
001289 NOD/ShiLt

Ighm^tm1Cgn

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

Tg(IghelMD4)4Ccg

Allele Type
Transgenic (Inserted expressed sequence)

View Genetics

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

NOD.Cg-Ighm^tm1Cgn Tg(IghelMD4)4Ccg/DvsJ (NOD.IgHEL Ighm-deficient) mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Because these mice are Ighm-deficient, they do not express endogenous IgM. All B lymphocytes in NOD.IgHEL Ighm-deficient mice express Ig molecules specific for hen egg lyzozyme (HEL). There is no significant difference in the total number of B and T lymphocytes between NOD.IgHEL Ighm-deficient and NOD.IgHEL (Stock No. 006345) mice. The incidence of diabetes in transgenic vs. non-transgenic NOD.Ighm-deficient mice is similar by 21 weeks of age, (16.7% vs. 13.6%, respectively). Histological evaluation of 12 week old NOD.IgHEL Ighm-deficient mice shows that most mice have low levels of insulitis compared to NOD/ShiLt control mice, although an occasional animal had extensive insulitis. In addition, NOD.IgHEL Ighm-deficient mice develop lymphosarcomas after 20 weeks of age. This pathology is not observed in either NOD.Ighm-deficient or NOD.IgHEL transgenic mice.

This strain may be used to study defects in B-cell selection as it relates to Type 1 Diabetes.

Development

NOD.129S2-Ighm^tm1Cgn/Dvs (Stock No. 003903) at generation N10 was bred with NOD.B6-Tg(IghelMD4)4Ccg/Dvs (Stock No. 004253). The doubly heterozygous offspring were backcrossed to the former strain (Stock No. 003903) to make the strain homozygous for the Ighm^tm1Cgn mutation. Siblings were then intercrossed to make this strain additionally homozygous for Tg(IghelMD4)4Ccg. In 2006, The T1DR received this strain at generation N11F16.

Expression Data

Expressed Gene	Ighg, Immunoglobulin heavy chain (gamma polypeptide), mouse, laboratory
Site of Expression

Control Suggestions

Additional Information

Considerations for Choosing Controls

Selected References

Silveira PA; Johnson E; Chapman HD; Bui T; Tisch RM; Serreze DV. 2002. The preferential ability of B lymphocytes to act as diabetogenic APC in NOD mice depends on expression of self-antigen-specific immunoglobulin receptors. Eur J Immunol 32(12):3657-66. PubMed: 12516557 MGI: J:80859

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(IghelMD4)4Ccg

Allele Symbol: Tg(IghelMD4)4Ccg

Allele Name	transgene insertion 4, Christopher C Goodnow
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	HELmuMT; Hel-Ig; Ig-transgenic; Ig^HEL; Ig^Tg; MD-3; MD4; MD4 HEL Ig; MD4 Ig; MD4 Ig BCR Tg; MD4-RAG; SWHEL
Gene Symbol and Name	Tg(IghelMD4)4Ccg, transgene insertion 4, Christopher C Goodnow
Gene Synonym(s)	HELmuMT; Hel-Ig; Ig-transgenic; Ig^HEL; MD-3; MD4; MD4 HEL Ig; MD4 Ig; MD4 Ig BCR Tg; MD4-RAG
Promoter	Ighg, Immunoglobulin heavy chain (gamma polypeptide), mouse, laboratory
Expressed Gene	Ighg, Immunoglobulin heavy chain (gamma polypeptide), mouse, laboratory
Strain of Origin	C57BL/6
Chromosome	17
Molecular Note	The hybridoma HyHEL10 produces an antibody with high affinity for hen egg lysozyme. Genomic clones encoding HyHEL10 immunoglobulin heavy and light chains were used for this construct. The gamma1-constant region of the heavy chain was replaced by a segment containing the mu and delta constant region genes derived from BALB/c mice. The light and heavy chains were co-injected into C57BL/6 eggs. Five lines, MD3-MD7, that carried multiple copies of the transgene construct were created. The MD4 line had the highest expression of the transgene and was propogated for further studies. Mice carrying this transgene had high serum titers of anti-lysozyme antibodies.
Mutations Made By	Dr. Christopher Goodnow, Stanford University 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) Analysis Strains
  - NOD Transgenics
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - 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(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg
NOD.Cg-Ighm^tm1Cgn Tg(IghelMD4)4Ccg/DvsJ

immune system phenotype

abnormal B lymphocyte antigen presentation
- purified B cells fail to stimulate T cells from non-transgenic NOD mice when cultured together in the presence of the diabetes autoantigen GAD

abnormal T cell proliferation
- T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD

abnormal mature B cell morphology
- all of the B cells express the transgenic IgM B cell receptor specific for hen egg lysozyme
- the number but not the proportion of B cells found in the spleen is twice that of non-transgenic NOD mice

decreased CD8-positive, alpha-beta T cell number
- the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice

decreased susceptibility to autoimmune diabetes
- 16.7% of female mice develop diabetes by 21 weeks of age compared to control NOD mice that have an incidence rate of 95.5% at this age
- mice with lymphosarcomas were not included in the analysis

insulitis
- mice have low levels of insulitis starting at 12 weeks of age with a mean disease score of 1.62 compared to non-transgenic NOD mice that have a mean score of 3.01 at this age

neoplasm

increased lymphoma incidence
- lymphosarcomas are present in the majority of mice with development starting at 20 weeks of age

hematopoietic system phenotype

abnormal B lymphocyte antigen presentation
- purified B cells fail to stimulate T cells from non-transgenic NOD mice when cultured together in the presence of the diabetes autoantigen GAD

abnormal T cell proliferation
- T cells fail to proliferate when splenocytes are cultured in vitro with the diabetes autoantigen GAD

abnormal mature B cell morphology
- all of the B cells express the transgenic IgM B cell receptor specific for hen egg lysozyme
- the number but not the proportion of B cells found in the spleen is twice that of non-transgenic NOD mice

decreased CD8-positive, alpha-beta T cell number
- the number of CD8 T cells found in the spleen is half that of non-transgenic NOD mice

endocrine/exocrine gland phenotype

insulitis
- mice have low levels of insulitis starting at 12 weeks of age with a mean disease score of 1.62 compared to non-transgenic NOD mice that have a mean score of 3.01 at this age

References

Silveira PA; Johnson E; Chapman HD; Bui T; Tisch RM; Serreze DV. 2002. The preferential ability of B lymphocytes to act as diabetogenic APC in NOD mice depends on expression of self-antigen-specific immunoglobulin receptors. Eur J Immunol 32(12):3657-66. PubMed: 12516557 MGI: J:80859

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
Ali M; Weinreich M; Balcaitis S; Cooper CJ; Fink PJ. 2003. Differential regulation of peripheral CD4+ T cell tolerance induced by deletion and TCR revision. J Immunol 171(11):6290-6. PubMed: 14634147 MGI: J:132828
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
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Also Known As: NOD.IgHEL,Igh-/-, NOD.IgHEL.Igμnull, NOD.IgHEL.Igu

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Ighmtm1Cgn

Allele Symbol: Ighmtm1Cgn

Tg(IghelMD4)4Ccg

Allele Symbol: Tg(IghelMD4)4Ccg

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

Genotype: Ighmtm1Cgn related

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Genotype: Ighmtm1Cgn/Ighmtm1Cgn Tg(IghelMD4)4Ccg/Tg(IghelMD4)4CcgNOD.Cg-Ighmtm1Cgn Tg(IghelMD4)4Ccg/DvsJ

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Also Known As: NOD.IgHEL,Igh-/-, NOD.IgHEL.Igμ^null, NOD.IgHEL.Igu

Ighm^tm1Cgn

Allele Symbol: Ighm^tm1Cgn

Genotype: Ighm^tm1Cgn related

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn Tg(IghelMD4)4Ccg/Tg(IghelMD4)4Ccg
NOD.Cg-Ighm^tm1Cgn Tg(IghelMD4)4Ccg/DvsJ

Additional - Ighm^tm1Cgn related