Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   06-JAN-09 Species laboratory mouse Generation N11+N1F13 (30-APR-13) Generation Definitions   Donating Investigator Kathryn Calame,   Columbia University

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.

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 Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Prdm1

008828	B6.Cg-Tg(Prdm1-EYFP)1Mnz/J
008827	B6.Cg-Tg(Prdm1-cre)1Masu/J

View Strains carrying other alleles of Prdm1     (2 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Cd19^tm1(cre)Cgn/Cd19⁺ Prdm1^tm1Clme/Prdm1^tm1Clme

        involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ   (conditional)

• immune system phenotype
• abnormal B cell differentiation
  • following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice   (MGI Ref ID J:101890)
  • a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization   (MGI Ref ID J:101890)
• • abnormal plasma cell differentiation
    • the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants   (MGI Ref ID J:101890)
• 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   (MGI Ref ID J:101890)
• abnormal plasma cell morphology   (MGI Ref ID J:101890)
  • 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   (MGI Ref ID J:114881)
• • abnormal plasma cell differentiation
    • the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants   (MGI Ref ID J:101890)
  • decreased plasma cell number
    • very few CD138+B220+/- plasma cells are seen at any time before or after immunization   (MGI Ref ID J:101890)
    • 5 days after re-challenge a 99% reduction in CD138+ B220+/- NP+ plasma cells is seen   (MGI Ref ID J:101890)
• decreased immunoglobulin level
  • serum Ig levels are reduced in unimmunized mice   (MGI Ref ID J:101890)
• • 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   (MGI Ref ID J:101890)
  • 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   (MGI Ref ID J:101890)
• increased spleen germinal center number
  • more numerous germinal centers are seen after immunization   (MGI Ref ID J:101890)
• increased spleen germinal center size
  • larger germinal centers are seen after immunization   (MGI Ref ID J:101890)
• hematopoietic system phenotype
• abnormal B cell differentiation
  • following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice   (MGI Ref ID J:101890)
  • a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization   (MGI Ref ID J:101890)
• • abnormal plasma cell differentiation
    • the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants   (MGI Ref ID J:101890)
• 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   (MGI Ref ID J:101890)
• abnormal plasma cell morphology   (MGI Ref ID J:101890)
  • 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   (MGI Ref ID J:114881)
• • abnormal plasma cell differentiation
    • the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants   (MGI Ref ID J:101890)
  • decreased plasma cell number
    • very few CD138+B220+/- plasma cells are seen at any time before or after immunization   (MGI Ref ID J:101890)
    • 5 days after re-challenge a 99% reduction in CD138+ B220+/- NP+ plasma cells is seen   (MGI Ref ID J:101890)
• increased spleen germinal center number
  • more numerous germinal centers are seen after immunization   (MGI Ref ID J:101890)
• increased spleen germinal center size
  • larger germinal centers are seen after immunization   (MGI Ref ID J:101890)
• cellular phenotype
• abnormal B cell differentiation
  • following immunization a severe decrease in the number of antigen-specific IgM secreting cells is seen compared to wild-type mice   (MGI Ref ID J:101890)
  • a larger increase in CD138-B220+NP+ B cells expressing GL7 is seen at 7 and 14 days after immunization   (MGI Ref ID J:101890)
• • abnormal plasma cell differentiation
    • the development of both short-lived and post-germinal center long-lived plasma cells is blocked in mutants   (MGI Ref ID J:101890)

View Research Applications

Research Applications

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

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Prdm1tm1Clme
Allele Name		targeted mutation 1, Kathryn Calame
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Blimp-1flox; Prdm1flox;
Mutation Made By		Kathryn Calame,   Columbia University
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Prdm1, PR domain containing 1, with ZNF domain
Chromosome		10
Gene Common Name(s)		B lymphocyte induced maturation protein; BLIMP1; Blimp-1; Blimp1; PRDI-BF1;
Molecular Note		LoxP sites were inserted to flank exons 6-8, encompassing sequence that encodes the zinc finger motifs. [MGI Ref ID J:101890]

Genotyping

Genotyping Information

Genotyping Protocols

Prdm1^tm1Clme, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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):607-20. [PubMed: 14563324]  [MGI Ref ID J:101890]

Additional References

Prdm1^tm1Clme related

Brzezinski JA 4th; Lamba DA; Reh TA. 2010. Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development. Development 137(4):619-29. [PubMed: 20110327]  [MGI Ref ID J:156665]

Chan YH; Chiang MF; Tsai YC; Su ST; Chen MH; Hou MS; Lin KI. 2009. Absence of the transcriptional repressor Blimp-1 in hematopoietic lineages reveals its role in dendritic cell homeostatic development and function. J Immunol 183(11):7039-46. [PubMed: 19915049]  [MGI Ref ID J:157392]

Cimmino L; Martins GA; Liao J; Magnusdottir E; Grunig G; Perez RK; Calame KL. 2008. Blimp-1 attenuates Th1 differentiation by repression of ifng, tbx21, and bcl6 gene expression. J Immunol 181(4):2338-47. [PubMed: 18684923]  [MGI Ref ID J:140193]

Gururajan M; Simmons A; Dasu T; Spear BT; Calulot C; Robertson DA; Wiest DL; Monroe JG; Bondada S. 2008. Early growth response genes regulate B cell development, proliferation, and immune response. J Immunol 181(7):4590-602. [PubMed: 18802061]  [MGI Ref ID J:141295]

Harper J; Mould A; Andrews RM; Bikoff EK; Robertson EJ. 2011. The transcriptional repressor Blimp1/Prdm1 regulates postnatal reprogramming of intestinal enterocytes. Proc Natl Acad Sci U S A 108(26):10585-90. [PubMed: 21670299]  [MGI Ref ID J:173543]

Horsley V; O'Carroll D; Tooze R; Ohinata Y; Saitou M; Obukhanych T; Nussenzweig M; Tarakhovsky A; Fuchs E. 2006. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell 126(3):597-609. [PubMed: 16901790]  [MGI Ref ID J:115995]

Iwasaki Y; Fujio K; Okamura T; Yanai A; Sumitomo S; Shoda H; Tamura T; Yoshida H; Charnay P; Yamamoto K. 2013. Egr-2 transcription factor is required for Blimp-1-mediated IL-10 production in IL-27-stimulated CD4(+) T cells. Eur J Immunol 43(4):1063-73. [PubMed: 23349024]  [MGI Ref ID J:195056]

Johnston RJ; Choi YS; Diamond JA; Yang JA; Crotty S. 2012. STAT5 is a potent negative regulator of TFH cell differentiation. J Exp Med 209(2):243-50. [PubMed: 22271576]  [MGI Ref ID J:181874]

Katoh K; Omori Y; Onishi A; Sato S; Kondo M; Furukawa T. 2010. Blimp1 suppresses Chx10 expression in differentiating retinal photoreceptor precursors to ensure proper photoreceptor development. J Neurosci 30(19):6515-26. [PubMed: 20463215]  [MGI Ref ID J:160529]

Kim SJ; Zou YR; Goldstein J; Reizis B; Diamond B. 2011. Tolerogenic function of Blimp-1 in dendritic cells. J Exp Med 208(11):2193-9. [PubMed: 21948081]  [MGI Ref ID J:178876]

Lin MH; Chou FC; Yeh LT; Fu SH; Chiou HY; Lin KI; Chang DM; Sytwu HK. 2013. B lymphocyte-induced maturation protein 1 (BLIMP-1) attenuates autoimmune diabetes in NOD mice by suppressing Th1 and Th17 cells. Diabetologia 56(1):136-46. [PubMed: 23052053]  [MGI Ref ID J:194560]

Lord CA; Savitsky D; Sitcheran R; Calame K; Wright JR; Ting JP; Williams KL. 2009. Blimp-1/PRDM1 mediates transcriptional suppression of the NLR gene NLRP12/Monarch-1. J Immunol 182(5):2948-58. [PubMed: 19234190]  [MGI Ref ID J:146247]

Magnusdottir E; Kalachikov S; Mizukoshi K; Savitsky D; Ishida-Yamamoto A; Panteleyev AA; Calame K. 2007. Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1. Proc Natl Acad Sci U S A 104(38):14988-93. [PubMed: 17846422]  [MGI Ref ID J:125198]

Martins GA; Cimmino L; Liao J; Magnusdottir E; Calame K. 2008. Blimp-1 directly represses Il2 and the Il2 activator Fos, attenuating T cell proliferation and survival. J Exp Med 205(9):1959-65. [PubMed: 18725523]  [MGI Ref ID J:138810]

Martins GA; Cimmino L; Shapiro-Shelef M; Szabolcs M; Herron A; Magnusdottir E; Calame K. 2006. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Nat Immunol 7(5):457-65. [PubMed: 16565721]  [MGI Ref ID J:112556]

Muto A; Ochiai K; Kimura Y; Itoh-Nakadai A; Calame KL; Ikebe D; Tashiro S; Igarashi K. 2010. Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch. EMBO J 29(23):4048-61. [PubMed: 20953163]  [MGI Ref ID J:167182]

Nishikawa K; Nakashima T; Hayashi M; Fukunaga T; Kato S; Kodama T; Takahashi S; Calame K; Takayanagi H. 2010. Blimp1-mediated repression of negative regulators is required for osteoclast differentiation. Proc Natl Acad Sci U S A 107(7):3117-22. [PubMed: 20133620]  [MGI Ref ID J:157572]

Omori SA; Cato MH; Anzelon-Mills A; Puri KD; Shapiro-Shelef M; Calame K; Rickert RC. 2006. Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling. Immunity 25(4):545-57. [PubMed: 17000121]  [MGI Ref ID J:114881]

Pan H; O'Brien TF; Zhang P; Zhong XP. 2012. The role of tuberous sclerosis complex 1 in regulating innate immunity. J Immunol 188(8):3658-66. [PubMed: 22412198]  [MGI Ref ID J:184070]

Pelletier N; McHeyzer-Williams LJ; Wong KA; Urich E; Fazilleau N; McHeyzer-Williams MG. 2010. Plasma cells negatively regulate the follicular helper T cell program. Nat Immunol 11(12):1110-8. [PubMed: 21037578]  [MGI Ref ID J:167325]

Robertson EJ; Charatsi I; Joyner CJ; Koonce CH; Morgan M; Islam A; Paterson C; Lejsek E; Arnold SJ; Kallies A; Nutt SL; Bikoff EK. 2007. Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice. Development 134(24):4335-45. [PubMed: 18039967]  [MGI Ref ID J:129204]

Salehi S; Bankoti R; Benevides L; Willen J; Couse M; Silva JS; Dhall D; Meffre E; Targan S; Martins GA. 2012. B Lymphocyte-Induced Maturation Protein-1 Contributes to Intestinal Mucosa Homeostasis by Limiting the Number of IL-17-Producing CD4+ T Cells. J Immunol 189(12):5682-93. [PubMed: 23162130]  [MGI Ref ID J:190850]

Savitsky D; Calame K. 2006. B-1 B lymphocytes require Blimp-1 for immunoglobulin secretion. J Exp Med 203(10):2305-14. [PubMed: 16954370]  [MGI Ref ID J:124626]

Shapiro-Shelef M; Lin KI; Savitsky D; Liao J; Calame K. 2005. Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow. J Exp Med 202(11):1471-6. [PubMed: 16314438]  [MGI Ref ID J:118853]

Sun J; Dodd H; Moser EK; Sharma R; Braciale TJ. 2011. CD4(+) T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol 12(4):327-34. [PubMed: 21297642]  [MGI Ref ID J:170347]

Vincent SD; Dunn NR; Sciammas R; Shapiro-Shalef M; Davis MM; Calame K; Bikoff EK; Robertson EJ. 2005. The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse. Development 132(6):1315-25. [PubMed: 15750184]  [MGI Ref ID J:101718]

Vincent SD; Mayeuf A; Niro C; Saitou M; Buckingham M. 2012. Non Conservation of Function for the Evolutionarily Conserved Prdm1 Protein in the Control of the Slow Twitch Myogenic Program in the Mouse Embryo. Mol Biol Evol :. [PubMed: 22522309]  [MGI Ref ID J:186268]

Yang Z; Sullivan BM; Allen CD. 2012. Fluorescent in vivo detection reveals that IgE(+) B cells are restrained by an intrinsic cell fate predisposition. Immunity 36(5):857-72. [PubMed: 22406270]  [MGI Ref ID J:187336]

Yoon HS; Scharer CD; Majumder P; Davis CW; Butler R; Zinzow-Kramer W; Skountzou I; Koutsonanos DG; Ahmed R; Boss JM. 2012. ZBTB32 is an early repressor of the CIITA and MHC class II gene expression during B cell differentiation to plasma cells. J Immunol 189(5):2393-403. [PubMed: 22851713]  [MGI Ref ID J:189853]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   06-JAN-09
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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.

See Terms of Use tab for General Terms and Conditions

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.

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