Overview

This Gadd45b targeted mutation strain may be useful in studies of autoimmune disease.

Donating Investigator

Binfeng Lu, University of Pittsburgh

Genetic overview

Genetic Background	Generation

Gadd45b^tm1Flv

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Gadd45b	growth arrest and DNA-damage-inducible 45 beta

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Apoptosis Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Isolated T cells exhibit increased proliferation with activation. Th1 cells from homozygotes are more resistant to activation induced apoptosis. 10 month old homozygotes exhibit mild splenomegaly. Homozygotes are more susceptible to experimental autoimmune encephalomyelitis, with longer duration and severity: 60% of homozygotes die when challenged with a higher dose of heat-inactivated Mycobacterium tuberculosis, compared to no deaths in controls. Immunocomplex deposits develop in the glomeruli of homozygotes.

Development

A targeting vector containing a Neo cassette was used to disrupt exons 3 and 4. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony. In January 2011, 32 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed that this strain is segregating at 5 markers likely from a mix of B6 and 129.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Lu B; Ferrandino AF; Flavell RA. 2004. Gadd45beta is important for perpetuating cognate and inflammatory signals in T cells. Nat Immunol 5(1):38-44PubMed: 14691480 MGI: J:87396

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Genetics

Gadd45b^tm1Flv

Allele Symbol: Gadd45b^tm1Flv

Allele Name	targeted mutation 1, Richard A Flavell
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Gadd45b^-
Gene Symbol and Name	Gadd45b, growth arrest and DNA-damage-inducible 45 beta
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	10
Molecular Note	Exons 3 and 4 were replaced with a neomycin selection cassette inserted by homologous recombination. The deleted region encoded residues 42 through 161, which make up crucial domains of the protein.
Mutations Made By	Binfeng Lu, University of Pittsburgh

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - experimental allergic encephalomyelitis (EAE)
Research Tools
- Apoptosis Research
Apoptosis Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Gadd45b^tm1Flv/Gadd45b^tm1Flv
involves: 129S6/SvEvTac

immune system phenotype

decreased interleukin-6 secretion
- there is a large reduction in IL-6 production by dendritic cells after low dose LPS stimulation

abnormal T-helper 2 physiology
- polarized Th2 CD4 T cells secrete about half as much IL-4 as controls

abnormal T-helper 1 physiology
- IFN-gamma secretion by Th1-polarized CD4 T cells is also reduced greatly
- IL-2 secretion by Th1-polarized CD4 T cells is about one-third of that in controls

decreased interferon-gamma secretion
- IFN-gamma secretion by Th1-polarized CD4 T cells is about one-fifth of that in controls
- reductions in IFN-gamma secretion are more dramatic when Th1 T cells are stimulated with IL-12 and IL-18 compared to controls

decreased interleukin-12 secretion
- there is a large reduction in IL-12 production by dendritic cells after low dose LPS stimulation

decreased interleukin-2 secretion
- similar defects in IL-2 secretion are observed for Th1-polarized CD4 T cells
- IL-2 secretion by na¿ve CD4 T cells is about one-third of that in controls

abnormal CD4-positive, alpha-beta T cell physiology
- IL-2 secretion by na¿ve CD4 T cells is about one-third of that in controls

abnormal T-helper 1 cell differentiation
- similar reductions in Th1 T cell production are found after infection with Listera monocytogenes
- there is a 2- to 3- fold reduction in the number of Th1 T cells produced in vivo after immunization with keyhole limpet hemocyanin

decreased interleukin-4 secretion
- polarized Th2 CD4 T cells secrete about half as much IL-4 as controls

abnormal dendritic cell physiology
- dendritic cells produce less IL-6 and IL-12 after activation by low doses of LPS

hematopoietic system phenotype

abnormal T-helper 1 physiology
- IL-2 secretion by Th1-polarized CD4 T cells is about one-third of that in controls
- IFN-gamma secretion by Th1-polarized CD4 T cells is also reduced greatly

abnormal CD4-positive, alpha-beta T cell physiology
- IL-2 secretion by na¿ve CD4 T cells is about one-third of that in controls

abnormal T-helper 1 cell differentiation
- similar reductions in Th1 T cell production are found after infection with Listera monocytogenes
- there is a 2- to 3- fold reduction in the number of Th1 T cells produced in vivo after immunization with keyhole limpet hemocyanin

abnormal T-helper 2 physiology
- polarized Th2 CD4 T cells secrete about half as much IL-4 as controls

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

Genotype: Gadd45b^tm1Flv/Gadd45b^tm1Flv
B6.129S6-Gadd45b

cellular phenotype

increased T cell proliferation
- na¿ve and Th1 CD4⁺ T cells have a higher rate of proliferation when activated in vitro

growth/size/body region phenotype

spleen hyperplasia
- mice develop mild splenomegaly around 10 months of age

renal/urinary system phenotype

renal glomerular immunoglobulin deposits

glomerulonephritis
- immune complex deposits are found in the glomeruli of 10 month old mice

hematopoietic system phenotype

abnormal T-helper 1 physiology
- proliferation rate is increased even more when Th1 cells are activated in the presence of IL-12 and IL-18
- Th1 T cells are resistant to activation-induced cell death caused by TCR stimulus without co-stimulation
- Th1 T cells proliferate at a faster rate when activated in vitro
- there is increased production of IFN-gamma by transplanted mutant T cells in the central nervous system of immunocompromised mice that have induced EAE

spleen hyperplasia
- mice develop mild splenomegaly around 10 months of age

increased T cell proliferation
- na¿ve and Th1 CD4⁺ T cells have a higher rate of proliferation when activated in vitro

immune system phenotype

abnormal T-helper 1 physiology
- proliferation rate is increased even more when Th1 cells are activated in the presence of IL-12 and IL-18
- Th1 T cells are resistant to activation-induced cell death caused by TCR stimulus without co-stimulation
- Th1 T cells proliferate at a faster rate when activated in vitro
- there is increased production of IFN-gamma by transplanted mutant T cells in the central nervous system of immunocompromised mice that have induced EAE

increased susceptibility to experimental autoimmune encephalomyelitis
- mice have a longer duration of peak disease than controls when mice are immunized with MOG peptide and a low dose of adjuvant
- 71% of mice transplanted with mutant CD4⁺ T cells die from EAE after immunization compared to 14% for hosts with wild-type CD4⁺ T cells
- 100% of immunocompromised mice transplanted with mutant CD4⁺ T cells develop EAE after immunization compared to 43% of mice that were recipients of wild-type mice
- 60% of mice die compared to none of controls when mice have EAE induced with MOG peptide and a high dose of adjuvant

increased T cell proliferation
- na¿ve and Th1 CD4⁺ T cells have a higher rate of proliferation when activated in vitro

glomerulonephritis
- immune complex deposits are found in the glomeruli of 10 month old mice

spleen hyperplasia
- mice develop mild splenomegaly around 10 months of age

increased interferon-gamma secretion
- there is increased production of IFN-gamma by transplanted mutant T cells in the central nervous system of immunocompromised mice that have induced EAE

References

Lu B; Ferrandino AF; Flavell RA. 2004. Gadd45beta is important for perpetuating cognate and inflammatory signals in T cells. Nat Immunol 5(1):38-44PubMed: 14691480 MGI: J:87396

Additional - Gadd45b^tm1Flv related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Gadd45b
- Standard PCR:Gadd45b
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129S6-Gadd45b^tm1Flv/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013101 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
> >	Heterozygous for Gadd45b<tm1Flv>

Related Products and Services

Frozen Mouse Embryo	B6;129S6-Gadd45b<tm1Flv>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129S6-Gadd45b<tm1Flv>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129S6-Gadd45b<tm1Flv>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6;129S6-Gadd45b<tm1Flv>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

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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

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Gadd45btm1Flv

Allele Symbol: Gadd45btm1Flv

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Gadd45btm1Flv/Gadd45btm1Flvinvolves: 129S6/SvEvTac

immune system phenotype

hematopoietic system phenotype

Genotype: Gadd45btm1Flv/Gadd45btm1FlvB6.129S6-Gadd45b

cellular phenotype

growth/size/body region phenotype

renal/urinary system phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional - Gadd45btm1Flv related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Gadd45b^tm1Flv

Allele Symbol: Gadd45b^tm1Flv

Genotype: Gadd45b^tm1Flv/Gadd45b^tm1Flv
involves: 129S6/SvEvTac

Genotype: Gadd45b^tm1Flv/Gadd45b^tm1Flv
B6.129S6-Gadd45b

Additional - Gadd45b^tm1Flv related