Overview

Also Known As:Prdm1^F

These Prdm1 floxed conditional mutant mice may be useful in generating conditional mutations to study humoral immune response, plasma memory B-cells, and B-lymphocyte development and differentiation.

Donating Investigator

Kathryn Calame, Columbia University

Genetic overview

Genetic Background	Generation

Prdm1^tm1Clme

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Prdm1	PR domain containing 1, with ZNF domain

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Research Applications

Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These mice possess loxP sites in introns flanking exons 6 to 8 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 6 to 8 deleted in the cre-expressing tissue(s).

When bred to a strain expressing Cre recombinase during B-lymphocyte development and differentiation (see Stock No. 004126 for example), this mutant mouse strain may be useful in studies of humoral immune response.

When bred to mice carrying Tg(Itgax-cre)1-1Reiz (Stock No. 008068), Cre recombinase expression in dendritic cells results in altered adaptive immune response and lupus-like serology.

Development

A targeting vector containing a loxP site flanked neomycin selection cassette and a herpes simplex virus thymidine kinase gene was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 8 of the targeted gene, and another loxP site was inserted downstream of exon 5. This construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid for the purpose of removing the selectable marker cassette. ES cells that had successfully undergone Cre recombination and no longer retained the cassette but did retain the loxP-flanked exons 6-8 were injected in C57BL/6J blastocysts. Resulting chimeric animals were backcrossed to C57BL/6J for 10 generations before arriving at The Jackson Laboratory.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Shapiro-Shelef M; Lin KI; McHeyzer-Williams LJ; Liao J; McHeyzer-Williams MG; Calame K. 2003. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19(4):607-20PubMed: 14563324 MGI: J:101890

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Genetics

Prdm1^tm1Clme

Allele Symbol: Prdm1^tm1Clme

Allele Name	targeted mutation 1, Kathryn Calame
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Blimp-1flox; Prdm1^CA; Prdm1^flox
Gene Symbol and Name	Prdm1, PR domain containing 1, with ZNF domain
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	10
Molecular Note	LoxP sites were inserted to flank exons 6-8, encompassing sequence that encodes the zinc finger motifs.
Mutations Made By	Kathryn Calame, Columbia University

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

systemic lupus erythematosus

Research Areas By Phenotype

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

Research Tools
- Developmental Biology Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences

Mammalian Phenotype Terms by Genotype

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

Genotype: Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Itgax-cre)1-1Reiz/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

hematopoietic system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- increase in expression of ICOS in CD4+ T cells, indicating that mice have more activated CD4+ T cells than controls

increased splenocyte number
- total number of splenocytes are increased in females but not males

increased germinal center B cell number
- more spontaneous germinal center B cells

increased T follicular helper cell number
- increase in the percentage and number of follicular T helper cells

increased spleen germinal center number
- more germinal centers in the spleen

increased IgG level
- kidney deposition of IgG in 10 month old females

abnormal T follicular helper cell differentiation
- generation of follicular T helper cells cells is enhanced when mutant dendritic cells are cultured with naive T cells from control mice in the presence of differentiation factors, indicating increased differentiation of these cells

increased immunoglobulin level
- total serum immunoglobulin levels are increased in females but not males

abnormal germinal center B cell physiology
- enhanced germinal center response in young mice

homeostasis/metabolism phenotype

increased urine protein level
- proteinuria in 10 month old females

immune system phenotype

abnormal CD4-positive, alpha-beta T cell physiology
- increase in expression of ICOS in CD4+ T cells, indicating that mice have more activated CD4+ T cells than controls

increased splenocyte number
- total number of splenocytes are increased in females but not males

abnormal immune system physiology
- enhanced immune response after NP-CGG immunization with an increased high-affinity anti-NP IgG response, an increase in the number of germinal center B cells, and an increase in the number of total germinal cells and antigen-specific germinal cells

increased anti-double stranded DNA antibody level
- IgG2b is the major isotype of anti-dsDNA antibodies

increased T follicular helper cell number
- increase in the percentage and number of follicular T helper cells

increased immunoglobulin level
- total serum immunoglobulin levels are increased in females but not males

increased interleukin-6 secretion
- increase in production of IL-6 by splenic dendritic cells and by bone marrow derived dendritic cells after LPS stimulation in females but not males

kidney inflammation
- inflammatory infiltrates in 10 month old females

increased anti-nuclear antigen antibody level

increased autoantibody level
- females, but not males, develop autoantibodies as early as 4-5 months of age, including anti-nuclear antibodies, anti-double stranded dNA, and anti-ENA5, which are all IgG

abnormal germinal center B cell physiology
- enhanced germinal center response in young mice

abnormal T follicular helper cell differentiation
- generation of follicular T helper cells cells is enhanced when mutant dendritic cells are cultured with naive T cells from control mice in the presence of differentiation factors, indicating increased differentiation of these cells

increased germinal center B cell number
- more spontaneous germinal center B cells

increased IgG level
- kidney deposition of IgG in 10 month old females

increased spleen germinal center number
- more germinal centers in the spleen

renal/urinary system phenotype

abnormal mesangial cell morphology
- mesangial cell proliferation in 10 month old females

abnormal kidney morphology
- kidney deposition of IgG in 10 month old females

increased urine protein level
- proteinuria in 10 month old females

kidney inflammation
- inflammatory infiltrates in 10 month old females

Genotype: Cd19^tm1(cre)Cgn/Cd19⁺ Prdm1^tm1Clme/Prdm1^tm1Clme
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

immune system phenotype

abnormal plasma cell morphology
- antibody stimulating cell development is completely inhibited in cultures of stimulated B cells, however stimulation of B cells with LPS or LPS and IL-4 results in increased class switch recombination

increased spleen germinal center size
- larger germinal centers are seen after immunization

abnormal B cell differentiation
- a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization
- following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice

abnormal plasma cell differentiation
- the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants

decreased immunoglobulin level
- serum Ig levels are reduced in unimmunized mice

decreased plasma cell number
- 5 days after re-challenge a 99% reduction in CD138+ B220+/- NP+ plasma cells is seen
- very few CD138+B220+/- plasma cells are seen at any time before or after immunization

decreased IgG level
- in mice immunized with NP-Ficoll serum IgG1 and IgG2a levels are significantly lower in mutants compared to wild-type mice and mutant mice fail to secrete Ig in a recall response

decreased IgM level
- in mice immunized with NP-Ficoll serum IgM levels are significantly lower in mutants compared to wild-type mice and homozygous mice fail to secrete Ig in a recall response

increased spleen germinal center number
- more numerous germinal centers are seen after immunization

abnormal memory B cell number
- pre-plasma memory B-cells are reduced by 75% in the spleen and 95% in the bone marrow, and CD138-B220+NP+ cells comprise the majority of memory B cells

hematopoietic system phenotype

abnormal memory B cell number
- pre-plasma memory B-cells are reduced by 75% in the spleen and 95% in the bone marrow, and CD138-B220+NP+ cells comprise the majority of memory B cells

abnormal plasma cell differentiation
- the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants

abnormal plasma cell morphology
- antibody stimulating cell development is completely inhibited in cultures of stimulated B cells, however stimulation of B cells with LPS or LPS and IL-4 results in increased class switch recombination

decreased plasma cell number
- 5 days after re-challenge a 99% reduction in CD138+ B220+/- NP+ plasma cells is seen
- very few CD138+B220+/- plasma cells are seen at any time before or after immunization

abnormal B cell differentiation
- a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization
- following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice

decreased IgG level
- in mice immunized with NP-Ficoll serum IgG1 and IgG2a levels are significantly lower in mutants compared to wild-type mice and mutant mice fail to secrete Ig in a recall response

increased spleen germinal center number
- more numerous germinal centers are seen after immunization

increased spleen germinal center size
- larger germinal centers are seen after immunization

decreased IgM level
- in mice immunized with NP-Ficoll serum IgM levels are significantly lower in mutants compared to wild-type mice and homozygous mice fail to secrete Ig in a recall response

decreased immunoglobulin level
- serum Ig levels are reduced in unimmunized mice

Genotype: Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Pdx1-cre)6Tuv/0
involves: 129S1/Sv * 129X1/SvJ * FVB/N

mammalian phenotype

endocrine/exocrine gland phenotype
- Normal - mice are viable and pancreata show no histologic changes

References

Shapiro-Shelef M; Lin KI; McHeyzer-Williams LJ; Liao J; McHeyzer-Williams MG; Calame K. 2003. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19(4):607-20PubMed: 14563324 MGI: J:101890

Additional - Prdm1^tm1Clme related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Prdm1
- 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 Prdm1^F mouse strain in a publication, please cite the originating article(s) and include JAX stock #008100 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

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

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> >	Heterozygous for Prdm1<tm1Clme>

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:Prdm1F

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Prdm1tm1Clme

Allele Symbol: Prdm1tm1Clme

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Prdm1tm1Clme/Prdm1tm1Clme Tg(Itgax-cre)1-1Reiz/0involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

renal/urinary system phenotype

Genotype: Cd19tm1(cre)Cgn/Cd19+ Prdm1tm1Clme/Prdm1tm1Clmeinvolves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

immune system phenotype

hematopoietic system phenotype

Genotype: Prdm1tm1Clme/Prdm1tm1Clme Tg(Pdx1-cre)6Tuv/0involves: 129S1/Sv * 129X1/SvJ * FVB/N

mammalian phenotype

References

Additional - Prdm1tm1Clme 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

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:Prdm1^F

Prdm1^tm1Clme

Allele Symbol: Prdm1^tm1Clme

Genotype: Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Itgax-cre)1-1Reiz/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

Genotype: Cd19^tm1(cre)Cgn/Cd19⁺ Prdm1^tm1Clme/Prdm1^tm1Clme
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

Genotype: Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Pdx1-cre)6Tuv/0
involves: 129S1/Sv * 129X1/SvJ * FVB/N

Additional - Prdm1^tm1Clme related