Overview

Also Known As: muMt^-

Mice homozygous for the Ighm^tm1Cgn knock-out mutation have a disruption of one of the membrane exons of the gene encoding immunoglobulin heavy chain of the class mu (IgM) and lack mature B-cells. These mice may be useful as a model for B-cell immunodeficiency found in humans.

Donating Investigator

Klaus Rajewsky, Max Delbruck Centre for Molecular Medicine

Genetic overview

Genetic Background	Generation

Ighm^tm1Cgn

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

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Ighm^tm1Cgn targeted mutation are viable and fertile. Homozygous mutant mice lack mature B-cells. There is no expression of membrane-bound IgM, although some B-cells may be produced using a C gene other than mu. It may be useful as a model for B-cell immunodeficiency found in humans. Also know as muMT.

Control Suggestions

000665 C57BL/10J

Additional Information

Considerations for Choosing Controls

Selected References

Kitamura D; Roes J; Kuhn R; Rajewsky K. 1991. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature 350(6317):423-6PubMed: 1901381 MGI: J:70398

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)	targeted mutation 1, University of Cologne; Ighm^tm1Cgn
Gene Symbol and Name	Ighm, immunoglobulin heavy constant mu
Gene Synonym(s)	BCR; AI326478; muH; muMT; immunoglobulin heavy chain 6 (heavy chain of IgM); IgM; Igh-6; Igh-M; Ig mu; immunoglobulin heavy chain mu; Igh-M; Igh6; expressed sequence AI326478
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

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

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 information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn
involves: 129S2/SvPas * C57BL/6

hematopoietic system phenotype

abnormal B cell differentiation
- in heterozygotes, normal numbers of B cells are produced, but there is loss of H-chain allelic exclusion; B cells producing H chains from both endogenous loci are detected, but such cells are absent in wild-type mice
- mutants appear to have large pre-B cells, but not small pre-B cells, indicating arrest of differentiation at the pre-B cell stage at or close to the transition from the large to small pre-B cell

absent immature B cells

absent mature B cells
- no B cells are detected in the peritoneal cavity; no cells expressing IgM or IgD on their surface are detected in the peritoneal cavity
- peripheral blood and spleen lack mature B cells as shown by lack of CD45R(B220)^bright cells

arrested B cell differentiation
- development appears to arrest differentiation of B cells at or close to the transition from the large to small pre-B cell

decreased IgM level
- homozygotes have no detectable IgM in their serum compared to ~600ug IgM/ml in wild-type serum

mammalian phenotype

immune system phenotype
- mucosal-associated invariant T cells (MAIT) that are not found in mice lacking all B cells are found in normal amounts in these mice

respiratory system phenotype
- Normal - trachea of infected mice contain more mucin than infected wild-type tracheas

respiratory system phenotype

abnormal respiratory system physiology
- after 4 weeks, mice show absence of vascular remodeling of the airways in response to Mycoplasma pulmonis infection wherease wild-type show complex growth and reorganization of the vascular beds
- although epithelial cell hyperplasia is not observed, epithelial layer is abnormally elongated

immune system phenotype

abnormal B cell differentiation
- in heterozygotes, normal numbers of B cells are produced, but there is loss of H-chain allelic exclusion; B cells producing H chains from both endogenous loci are detected, but such cells are absent in wild-type mice
- mutants appear to have large pre-B cells, but not small pre-B cells, indicating arrest of differentiation at the pre-B cell stage at or close to the transition from the large to small pre-B cell

abnormal lymphatic vessel morphology
- upon infection with Mycoplasma pulmonis, airway lymphatic vessel remodeling is largely absent from mutants, compared to significant invasion of region by lymphatic vessels in infected wild-type mice

abnormal response to infection
- airway vascular and airway lymphatic vessel remodeling are impaired or absent compared to wild-type mice after M. pulmonis infection
- bacteria are present in liver and kidney of mice after 4 weeks of M. pulmonis infection, but bacteria are absent from wild-type mouse tissue

absent immature B cells

absent mature B cells
- no B cells are detected in the peritoneal cavity; no cells expressing IgM or IgD on their surface are detected in the peritoneal cavity
- peripheral blood and spleen lack mature B cells as shown by lack of CD45R(B220)^bright cells

arrested B cell differentiation
- development appears to arrest differentiation of B cells at or close to the transition from the large to small pre-B cell

decreased IgM level
- homozygotes have no detectable IgM in their serum compared to ~600ug IgM/ml in wild-type serum

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn
B6.129S2-Ighm/J

cardiovascular system phenotype

abnormal cardiovascular system physiology
- mutants are protected from developing elastase-induced abdominal aortic aneurysm

homeostasis/metabolism phenotype

decreased susceptibility to injury
- ible to abdominal aortic aneurysm
- mutants are protected from developing elastase-induced abdominal aortic aneurysm
- reconstitution of mutants with mouse natural antibodies from pooled sera of wild-type mice does not restore susceptibility to abdominal aortic aneurysm in mutants, however reconstitution with pooled mouse IgG to the wild-type level renders mutants susceptible to abdominal aortic aneurysm

immune system phenotype

abnormal cytokine secretion
- in mutants, Il-2 secretion is diminished from T cells primed in absence of B cells compared to controls 6 months after keyhole limpet hemocyanin immunization

abnormal humoral immune response
- mice fail to respond to T cell-dependent (OVA) or T cell-independent (dextra) antigenic stimulation and do not produce serum specific antibodies to these antigens

abnormal spleen morphology
- in mutants, area of T zone stromal cell network in the spleen is decreased four- to five-fold compared to wild-type
- T zone cross sectional area is decreased 2- to 3-fold

arrested B cell differentiation
- a transitional block in early B cell development in evident in bone marrow; pre-B cells are decreased in number

decreased CD4-positive, alpha beta T cell number
- numbers are reduced 3-fold in spleen vs wild-type
- there are 5- to 40-fold fewer antigen specific CD4 cells producing Il-2 in mutants compared to controls 6 months after keyhole limpet hemocyanin immunization

decreased CD8-positive, alpha-beta T cell number
- numbers are reduced 3-fold in spleen vs wild-type

decreased dendritic cell number
- numbers of CD11c+ dendritic cells (DCs) are reduced in mutants

decreased IgE level
- IgE is not detectable in serum of OVA-treated mutants, but high levels are produced in treated wild-type

decreased IgG level
- IgG is not detectable in OVA-treated mutants, but high levels are produced in treated wild-type
- IgG levels drop rapidly after birth due to loss of maternal Ig

decreased IgG1 level
- IgG1 is not detected in serum after OVA challenge

decreased immunoglobulin level
- null mice have almost undetectable serum levels of IgG1, IgG2a, IgG2b, IgG3, IgM and IgA compared to wild-type controls or Fas^lpr mice

decreased spleen weight
- spleens are ~50% the weight of wild-type spleens

increased susceptibility to parasitic infection
- mice are not protected from Giardia upon a secondary challenge as wild-type mice are
- mice fail to clear a Giardia muris infection
- mice have 10-fold more Giardia trophozoites in the small intestine three weeks after infection and a thousand-fold more 7 weeks after infection compared to controls
- mutant mice still have an active Giardia population in the gut one year after infection while wild-type mice clear Giardia after about 7 weeks
- two weeks after Giardia infection, there are 10-fold more Giardia cysts present in the feces of mice

hematopoietic system phenotype

abnormal spleen morphology
- in mutants, area of T zone stromal cell network in the spleen is decreased four- to five-fold compared to wild-type
- T zone cross sectional area is decreased 2- to 3-fold

arrested B cell differentiation
- a transitional block in early B cell development in evident in bone marrow; pre-B cells are decreased in number

decreased CD4-positive, alpha beta T cell number
- numbers are reduced 3-fold in spleen vs wild-type
- there are 5- to 40-fold fewer antigen specific CD4 cells producing Il-2 in mutants compared to controls 6 months after keyhole limpet hemocyanin immunization

decreased CD8-positive, alpha-beta T cell number
- numbers are reduced 3-fold in spleen vs wild-type

decreased dendritic cell number
- numbers of CD11c+ dendritic cells (DCs) are reduced in mutants

decreased IgE level
- IgE is not detectable in serum of OVA-treated mutants, but high levels are produced in treated wild-type

decreased IgG level
- IgG is not detectable in OVA-treated mutants, but high levels are produced in treated wild-type
- IgG levels drop rapidly after birth due to loss of maternal Ig

decreased IgG1 level
- IgG1 is not detected in serum after OVA challenge

decreased immunoglobulin level
- null mice have almost undetectable serum levels of IgG1, IgG2a, IgG2b, IgG3, IgM and IgA compared to wild-type controls or Fas^lpr mice

decreased spleen weight
- spleens are ~50% the weight of wild-type spleens

mammalian phenotype

immune system phenotype
- Normal - dendritic cells show normal function in mutants
- T cell numbers in lymph nodes are normal

respiratory system phenotype

abnormal respiratory system physiology
- ovalbumin-sensitized/challenged mice (OVA) are unable to generate an early phase reaction (EPR- initial phase of brochoconstriction) following OVA provocation

skeleton phenotype

abnormal compact bone morphology

abnormal trabecular bone morphology
- reduced number of trabeculae
- reduced trabecular bone structure in femora

decreased bone mineral density
- significantly decreased at 10 weeks of age

decreased compact bone thickness

decreased compact bone volume

decreased trabecular bone thickness

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn
involves: 129S2/SvPas

cellular phenotype

decreased T cell proliferation
- CD4⁺ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro

immune system phenotype

abnormal antigen presentation
- CD4⁺ T cells have normal primary responses suggesting lower T cell activity from immunized mice is a failure in antigen presentation

abnormal CD4-positive, alpha-beta T cell physiology
- CD4⁺ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro

abnormal metallophilic macrophage morphology
- marginal metallophilic macrophages are absent

abnormal spleen marginal sinus morphology
- sinus lining cells (MAdCAM-1+) are absent

abnormal spleen marginal zone macrophage morphology
- MARCO+ cells are absent

absent follicular dendritic cells
- follicular dendritic cells are absent

absent mature B cells
- in bone marrow and spleen, mature (B220+) B lymphocytes are lacking

arrested B cell differentiation
- B cell development is halted at pre-B cell stage, indicated by lack of CD25+ B-cells

decreased IgA level
- absent

decreased IgG level
- absent

decreased susceptibility to type IV hypersensitivity reaction
- footpad swelling of antigen-sensitized mice is less than controls

decreased T cell proliferation
- CD4⁺ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro

increased osteoclast cell number

increased susceptibility to induced arthritis

increased susceptibility to parasitic infection
- after second infestation to ticks, mice fail to exhibit resistance (repletion) unlike similarly treated wild-type mice

hematopoietic system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- CD4⁺ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro

abnormal metallophilic macrophage morphology
- marginal metallophilic macrophages are absent

abnormal spleen marginal sinus morphology
- sinus lining cells (MAdCAM-1+) are absent

abnormal spleen marginal zone macrophage morphology
- MARCO+ cells are absent

absent mature B cells
- in bone marrow and spleen, mature (B220+) B lymphocytes are lacking

arrested B cell differentiation
- B cell development is halted at pre-B cell stage, indicated by lack of CD25+ B-cells

decreased IgA level
- absent

decreased IgG level
- absent

decreased T cell proliferation
- CD4⁺ T cells isolated from antigen-challenged mice have reduced proliferation in response to antigen encounter in vitro

increased osteoclast cell number

skeleton phenotype

increased osteoclast cell number

increased susceptibility to induced arthritis

Genotype: Ighm^tm1Cgn/Ighm⁺
involves: 129S2/SvPas * C57BL/6

hematopoietic system phenotype

arrested B cell differentiation
- B cell development is arrested at the stage of pre-B cells

immune system phenotype

arrested B cell differentiation
- B cell development is arrested at the stage of pre-B cells

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn
B6.129S2-Ighm

digestive/alimentary phenotype

abnormal intestinal epithelium morphology
- migration of proliferated intestinal epithelial cells (IEC) toward the top of the villi and the number of proliferating IECs are augmented in mutants compared to wild-type controls
- treatment of mice with antibiotics results in deceleration of IEC migration and decreased proliferation compared to treated heterozygous controls

hematopoietic system phenotype

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
- population is ~2 times larger than in heterozygous controls

immune system phenotype

abnormal CD8 positive, alpha-beta intraepithelial T cell morphology
- population is ~2 times larger than in heterozygous controls

References

Kitamura D; Roes J; Kuhn R; Rajewsky K. 1991. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature 350(6317):423-6PubMed: 1901381 MGI: J:70398

Additional References

Kitamura D; Rajewsky K. 1992. Targeted disruption of mu chain membrane exon causes loss of heavy-chain allelic exclusion [see comments] Nature 356(6365):154-6PubMed: 1545868 MGI: J:64298

Additional - Ighm^tm1Cgn related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Ighm^tm1Cgn
- Standard PCR:Ighm^tm1Cgn
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes. The expected coat color from breeding is black.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the muMt^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002249 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	Genotype	Price
	Homozygous for Igh-6<tm1Cgn>, 1 pair minimum

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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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Also Known As: muMt-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

Selected References

Ighmtm1Cgn

Allele Symbol: Ighmtm1Cgn

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/Ighmtm1Cgninvolves: 129S2/SvPas * C57BL/6

hematopoietic system phenotype

mammalian phenotype

respiratory system phenotype

immune system phenotype

Genotype: Ighmtm1Cgn/Ighmtm1CgnB6.129S2-Ighm/J

cardiovascular system phenotype

homeostasis/metabolism phenotype

immune system phenotype

hematopoietic system phenotype

mammalian phenotype

respiratory system phenotype

skeleton phenotype

Genotype: Ighmtm1Cgn/Ighmtm1Cgninvolves: 129S2/SvPas

cellular phenotype

immune system phenotype

hematopoietic system phenotype

skeleton phenotype

Genotype: Ighmtm1Cgn/Ighm+involves: 129S2/SvPas * C57BL/6

hematopoietic system phenotype

immune system phenotype

Genotype: Ighmtm1Cgn/Ighmtm1CgnB6.129S2-Ighm

digestive/alimentary phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional References

Additional - Ighmtm1Cgn related

Genotyping Protocols

Breeding Considerations

Mating System

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: muMt^-

Ighm^tm1Cgn

Allele Symbol: Ighm^tm1Cgn

Genotype: Ighm^tm1Cgn related

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn
involves: 129S2/SvPas * C57BL/6

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn
B6.129S2-Ighm/J

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn
involves: 129S2/SvPas

Genotype: Ighm^tm1Cgn/Ighm⁺
involves: 129S2/SvPas * C57BL/6

Genotype: Ighm^tm1Cgn/Ighm^tm1Cgn
B6.129S2-Ighm

Additional - Ighm^tm1Cgn related