Strain Name:

B6.Cg-Spi1tm2Dgt/J

Stock Number:

006922

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.Cg-Sfpi1tm2Dgt/J    (Changed: 30-JUL-13 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN9+F2pN1
Generation Definitions
 
Donating Investigator Daniel G. Tenen,   Beth Israel Deaconess Medical Center

Important Note

NOTE: Despite these mice being backcrossed onto the C57BL/6 genetic background, occasional albino pups may be observed. The donating investigator confirms this observation and suggests the targeted mutation may have an as of yet uncharacterized effect upon coat color genes.

Description
Mice that are homozygous for this "PU.1F" conditional allele are viable and fertile. When PU.1F mice are bred to mice expressing Cre recombinase, exons 4-5 of the targeted gene are deleted in the cre-expressing tissues in the offspring. These mice may be useful in studying T cell lymphoma, AML and other cancers, as well as transcription factors, hematopoiesis, and the development of multiple cell lineages.

For example, when PU.1F mice are crossed with mice expressing the interferon- or dsRNA-inducible Mx1-cre transgenic mice (see Stock No. 003556), this mutant mouse strain may be useful in studies of hematopoietic stem cells.

NOTE: Despite these mice being backcrossed onto the C57BL/6 genetic background, occasional albino pups may be observed. The donating investigator confirms this observation and suggests the targeted mutation may have an as of yet uncharacterized effect upon coat color genes.

Development
A targeting vector was designed to insert loxp sites flanking exons 4-5 of the endogenous mouse PU.1 (or Sfpi1) gene, as well as a loxp-flanked PGK-neo cassette downstream of exon 5. This construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and the resulting chimeric males were bred to C57BL/6 females. These PU.1F mice were then backcrossed to C57BL/6 for at least 5 generations. At some point, these mice were bred with Mx1-Cre transgenic mice (congenic (N9) on a C57BL/6 background) and double mutant mice were subsequently sent to The Jackson Laboratory. Upon arrival, mice were selected for the PU.1F targeted mutation and (against the Mx1-Cre transgene) to establish this strain.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Spi1
006099   B6;129-Spi1tm1.2Dgt/J
006147   B6;FVB-Tg(Sfpi1,-EGFP)7Dgt/J
025244   C57BL/6N-Spi1tm2a(EUCOMM)Wtsi/J
006083   STOCK Spi1tm1.3Dgt/J
View Strains carrying other alleles of Spi1     (4 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

Spi1tm2Dgt/Spi1tm2Dgt

        B6.Cg-Spi1tm2Dgt
  • hematopoietic system phenotype
  • abnormal blood cell morphology/development
    • purified GMPs from homozygous mice transfected with retroviral transduction of cre form only colonies composed of myeloblasts   (MGI Ref ID J:114150)
    • cultured CMPs form megakaryocyte/erythroid colonies as well as myeloblast colonies that appear to replace GM-related colonies that form when normal CMPs are cultured   (MGI Ref ID J:114150)

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

Cd19tm1(cre)Cgn/Cd19+ Spi1tm2Dgt/Spi1tm2Dgt

        involves: 129P2/OlaHsd * C57BL/6   (conditional)
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype
    • mice have normal numbers of pre-B cells and mature B cells in the bone marrow   (MGI Ref ID J:114150)
    • B cells from the spleen show significant proliferative responses to mitogenic agents   (MGI Ref ID J:114150)

Spi1tm2Dgt/Spi1tm2Dgt Tg(Mx1-cre)1Cgn/0

        involves: 129P2/OlaHsd * C57BL/6 * CBA   (conditional)
  • hematopoietic system phenotype
  • abnormal blood cell morphology/development
    • 2-3 weeks after induction of cre expression with pI-pC, number of HSCs in bone marrow is decreased with loss of CMPs, GMPs and mature myeloid cells while MEPs are increased   (MGI Ref ID J:114150)
    • by 6 weeks, numbers of CLPs, CMPs, and GMPs begin to recover   (MGI Ref ID J:114150)
View Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation
Increased Tumor Incidence
      Leukemia

Developmental Biology Research
Internal/Organ Defects
      Lymphoid Tissue Defects
      hematopoietic defects

Hematological Research
Hematopoietic Defects

Immunology, Inflammation and Autoimmunity Research
Lymphoid Tissue Defects
      hematopoietic development

Internal/Organ Research
Lymphoid Tissue Defects

Research Tools
Cancer Research
      Leukemia
      tumor immunology
Cre-lox System
      loxP-flanked Sequences
Hematological Research
Immunology, Inflammation and Autoimmunity Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Spi1tm2Dgt
Allele Name targeted mutation 2, Daniel G Tenen
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) PU.1F;
Mutation Made By Daniel Tenen,   Beth Israel Deaconess Medical Center
Gene Symbol and Name Spi1, spleen focus forming virus (SFFV) proviral integration oncogene
Chromosome 2
Gene Common Name(s) Dis-1; PU.1; SFFV proviral integration 1; Sfpi-1; Sfpi1; Spi-1; Tcfpu1; Tfpu.1; transcription factor PU.1;
Molecular Note LoxP sites were inserted in intron 3 and a loxP-flanked neomycin selection cassette was inserted into intron 5. [MGI Ref ID J:114150]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Cre Melt Curve Analysis,

MELT


Generic Cre Melt Curve Analysis,

Probe


Sfpi1tm2Dgt, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Iwasaki H; Somoza C; Shigematsu H; Duprez EA; Iwasaki-Arai J; Mizuno S; Arinobu Y; Geary K; Zhang P; Dayaram T; Fenyus ML; Elf S; Chan S; Kastner P; Huettner CS; Murray R; Tenen DG; Akashi K. 2005. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood 106(5):1590-600. [PubMed: 15914556]  [MGI Ref ID J:114150]

Additional References

Spi1tm2Dgt related

Aikawa Y; Katsumoto T; Zhang P; Shima H; Shino M; Terui K; Ito E; Ohno H; Stanley ER; Singh H; Tenen DG; Kitabayashi I. 2010. PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nat Med 16(5):580-5, 1p following 585. [PubMed: 20418886]  [MGI Ref ID J:161535]

Hegde S; Hankey P; Paulson RF. 2012. Self-renewal of leukemia stem cells in friend virus-induced erythroleukemia requires proviral insertional activation of Spi1 and Hedgehog signaling but not mutation of p53. Stem Cells 30(2):121-30. [PubMed: 22083997]  [MGI Ref ID J:190190]

Laiosa CV; Stadtfeld M; Xie H; de Andres-Aguayo L; Graf T. 2006. Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBP alpha and PU.1 transcription factors. Immunity 25(5):731-44. [PubMed: 17088084]  [MGI Ref ID J:116118]

Mead AJ; Kharazi S; Atkinson D; Macaulay I; Pecquet C; Loughran S; Lutteropp M; Woll P; Chowdhury O; Luc S; Buza-Vidas N; Ferry H; Clark SA; Goardon N; Vyas P; Constantinescu SN; Sitnicka E; Nerlov C; Jacobsen SE. 2013. FLT3-ITDs Instruct a Myeloid Differentiation and Transformation Bias in Lymphomyeloid Multipotent Progenitors. Cell Rep 3(6):1766-76. [PubMed: 23727242]  [MGI Ref ID J:199313]

Sokalski KM; Li SK; Welch I; Cadieux-Pitre HA; Gruca MR; DeKoter RP. 2011. Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia. Blood 118(10):2801-8. [PubMed: 21768304]  [MGI Ref ID J:177088]

Staber PB; Zhang P; Ye M; Welner RS; Nombela-Arrieta C; Bach C; Kerenyi M; Bartholdy BA; Zhang H; Alberich-Jorda M; Lee S; Yang H; Ng F; Zhang J; Leddin M; Silberstein LE; Hoefler G; Orkin SH; Gottgens B; Rosenbauer F; Huang G; Tenen DG. 2013. Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells. Mol Cell 49(5):934-46. [PubMed: 23395001]  [MGI Ref ID J:196609]

Xu LS; Sokalski KM; Hotke K; Christie DA; Zarnett O; Piskorz J; Thillainadesan G; Torchia J; DeKoter RP. 2012. Regulation of B cell linker protein transcription by PU.1 and Spi-B in murine B cell acute lymphoblastic leukemia. J Immunol 189(7):3347-54. [PubMed: 22956576]  [MGI Ref ID J:190544]

Ye M; Ermakova O; Graf T. 2005. PU.1 is not strictly required for B cell development and its absence induces a B-2 to B-1 cell switch. J Exp Med 202(10):1411-22. [PubMed: 16301746]  [MGI Ref ID J:118844]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice are bred.

NOTE: Despite these mice being backcrossed onto the C57BL/6 genetic background, occasional albino pups may be observed. The donating investigator confirms this observation and suggests the targeted mutation may have an as of yet uncharacterized effect upon coat color genes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

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

Important Note

NOTE: Despite these mice being backcrossed onto the C57BL/6 genetic background, occasional albino pups may be observed. The donating investigator confirms this observation and suggests the targeted mutation may have an as of yet uncharacterized effect upon coat color genes.

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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.


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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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