Strain Name:

C57BL/6-Pmltm1(PML/RARA)Ley/J

Stock Number:

017959

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Availability:

Cryopreserved - Ready for recovery

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These mPML-PRflox mice express a Cre recombinase mediated PML-PARA fusion protein and may be useful in studies of acute promyelocytic leukemia.

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

Type Coisogenic; Mutant Strain; Targeted Mutation;
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Specieslaboratory mouse
GenerationN15pN1
Generation Definitions
 
Donating InvestigatorDr. Timothy J Ley,   Washington University School of Medicine

Description
The t(15;17)(q22:q11) translocation results in the PML-RARA, protein promyelocytic leukemia-retinoic acid receptor alpha, fusion gene, which is a characteristic chromosomal translocation in acute promyelocytic leukemia. These mPML-PRflox mice carry a loxP-flanked PGKneo-stop cassette, PML-RARA cDNA, in the 5' UTR of the Pml, promyelocytic leukemia, gene. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Pml gene product (protein) is detected by Western blot analysis of spleen cells from homozygous animals. When bred to mice that express Cre recombinase, resulting offspring will express the fusion oncoprotein PML-PARA in the cre-expressing tissue(s).

When bred to a strain with Cre recombinase expression in the myeloid cell lineage (see Stock No. 004781 for example), the resulting mice express PML/PARA mRNA in spleen cells and rare leukemia with acute promyelocytic leukemia characteristics.

When bred to a strain expressing tamoxifen-inducible Cre recombinase (see Stock No. 004682 for example), this mutant mouse strain may be useful in studies of hematopoietic stem cell renewal.

Development
A targeting vector containing a loxP-flanked PGKneo-stop cassette, PML-RARA cDNA, and 5 stop codons, was inserted into the Pml 5' untranslated region. The construct was electroporated into C57BL/6 derived B6-Blu embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The donating investigator reported that the resulting chimeric animals were crossed to C57BL/6 mice (see SNP note below). Upon arrival, heterozygous sperm was frozen. To generate the live colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Control Information

  Control
   000664 C57BL/6J (approximate)
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Acute Promyelocytic Leukemia; APL   (RARA)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Pmltm1(PML/RARA)Ley/Pml+

        involves: C57BL/6
  • normal phenotype
  • no abnormal phenotype detected
    • mice are viable with normal Mendelian inheritance and normal peripheral blood cell counts   (MGI Ref ID J:172024)

The following phenotype relates to a compound genotype created using this strain.
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Pmltm1(PML/RARA)Ley/Pml+ Lyz2tm1(cre)Ifo/Lyz2+

        involves: 129P2/OlaHsd * BALB/cJ * C57BL/6   (conditional)
  • tumorigenesis
  • increased leukemia incidence
    • one mouse exhibit rare leukemia with acute promyelocytic leukemia features   (MGI Ref ID J:172024)
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype
    • hematopoietic stem cells exhibit normal ex vivo self-renewal   (MGI Ref ID J:172024)

Pmltm1(PML/RARA)Ley/Pml+ Tg(CAG-cre/Esr1*)5Amc/0

        involves: BALB/cJ * C57BL/6 * CBA   (conditional)
  • hematopoietic system phenotype
  • abnormal hematopoietic stem cell physiology
    • hematopoietic stem cells from tamoxifen-treated mice exhibit in vitro self-renewal compared with control cells   (MGI Ref ID J:172024)
    • however, tamoxifen-treated mice do not exhibit myeloproliferative disease   (MGI Ref ID J:172024)
  • decreased hematopoietic stem cell number
    • small decrease in tamoxifen-treated mice   (MGI Ref ID J:172024)
  • enlarged spleen
    • in one tamoxifen-treated mouse   (MGI Ref ID J:172024)
  • immune system phenotype
  • enlarged spleen
    • in one tamoxifen-treated mouse   (MGI Ref ID J:172024)

Pmltm1(PML/RARA)Ley/Pml+ Tg(CMV-cre)1Cgn/Y

        involves: BALB/cJ * C57BL/6   (conditional)
  • mortality/aging
  • complete prenatal lethality
    • no mice are produced   (MGI Ref ID J:172024)

Pmltm1(PML/RARA)Ley/Pml+ Tg(Mx1-cre)1Cgn/0

        involves: C57BL/6 * CBA   (conditional)
  • mortality/aging
  • complete prenatal lethality
    • no mice are produced   (MGI Ref ID J:172024)
View Research Applications

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

Cancer Research
Other

Research Tools
Cancer Research
      Leukemia
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Pmltm1(PML/RARA)Ley
Allele Name targeted mutation 1, Timothy J Ley
Allele Type Targeted (knock-in)
Common Name(s) mPML-PRflox;
Mutation Made ByDr. Timothy Ley,   Washington University School of Medicine
Strain of OriginC57BL/6NTac-Tg(HBB-lacZ)ALey/Ley
Expressed Gene RARA, retinoic acid receptor, alpha, human
Expressed Gene PML, promyelocytic leukemia, human
Molecular Note A cassette, which contains a floxed neo resistance gene with five stop codons in three frames and a fusion of human PML and RARA, was inserted into the 5' untranslated region. The absence of protein expression was confirmed by western blot analysis on spleen cells. [MGI Ref ID J:172024]
 
 
Gene Symbol and Name Pml, promyelocytic leukemia
Chromosome 9
Gene Common Name(s) 1200009E24Rik; AI661194; MYL; PP8675; RGD1562602; RIKEN cDNA 1200009E24 gene; RNF71; TRIM19; expressed sequence AI661194;

Genotyping

Genotyping Information

Genotyping Protocols

Generic Neo Quantitative PCR-QPCR- 1.2, QPCR
Pmltm1(PML/RARA)Leyalternate2, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Welch JS; Yuan W; Ley TJ. 2011. PML-RARA can increase hematopoietic self-renewal without causing a myeloproliferative disease in mice. J Clin Invest 121(4):1636-45. [PubMed: 21364283]  [MGI Ref ID J:172024]

Additional References

Pmltm1(PML/RARA)Ley related

Maier NK; Crown D; Liu J; Leppla SH; Moayeri M. 2014. Arsenic trioxide and other arsenical compounds inhibit the NLRP1, NLRP3, and NAIP5/NLRC4 inflammasomes. J Immunol 192(2):763-70. [PubMed: 24337744]  [MGI Ref ID J:207325]

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, these mice can be bred as homozygotes.

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* $2085.00
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 11 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* $2710.50
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 11 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 (approximate)
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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