Overview

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

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

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

View All Research Applications

Base Price

Starting at:

$2,854.50 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):3657-66PubMed: 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; muIgKO; mum^-; muMT; muMt-; mu-MT^-
Gene Symbol and Name	Ighm, immunoglobulin heavy constant mu
Gene Synonym(s)
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)	Hel-Ig; HELmuMT; Ig^HEL; Ig^Tg; IgHEL; Ig-transgenic; 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)
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

No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

type 1 diabetes mellitus

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B cell defects
- Autoimmunity
  - Type 1 Diabetes
Diabetes and Obesity Research
- Type 1 Diabetes (IDDM) Analysis Strains
  - NOD Transgenics

Genotype: Ighm^tm1Cgn related

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

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

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

cellular phenotype

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

neoplasm

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

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

hematopoietic system phenotype

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

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

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

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

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

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

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

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):3657-66PubMed: 12516557 MGI: J:80859

Additional - Ighm^tm1Cgn related

Additional - Tg(IghelMD4)4Ccg related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ighm
- Standard PCR:Tg(IghelMD4)4Ccg Alternate1
- Standard PCR:Tg(IghelMD4)4Ccg
- Standard PCR:Ighm
- Genotyping resources and troubleshooting
Breeding Considerations

Female mice homozygous for the Ighm^tm1Cgn mutation and homozygous for the transgene are poor breeders, however males homozygous for the Ighm^tm1Cgn mutation and homozygous for the transgene breed well.
- Additional Breeding and Husbandry Support
Appearance
- pink-eyed, albino
  Related Genotype: A/A Tyr^c/Tyr^c
Citation
When using the NOD.IgHEL,Igh-/- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006608 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for Igh-6<tm1Cgn>, Hemizygous or Homozygous for Tg(IghelMD4)4Ccg

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:NOD.IgHEL.Igu, NOD.IgHEL.Igμnull, NOD.IgHEL,Igh-/-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Ighmtm1Cgn

Allele Symbol: Ighmtm1Cgn

Tg(IghelMD4)4Ccg

Allele Symbol: Tg(IghelMD4)4Ccg

Disease Terms

No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

Research Areas By Phenotype

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

Genotype: Ighmtm1Cgn related

Mammalian Phenotype Terms by Genotype

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

cellular phenotype

neoplasm

endocrine/exocrine gland phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional - Ighmtm1Cgn related

Additional - Tg(IghelMD4)4Ccg related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

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

Ighm^tm1Cgn

Allele Symbol: Ighm^tm1Cgn

Genotype: Ighm^tm1Cgn related

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

Additional - Ighm^tm1Cgn related