Description

Strain Information

Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   12-MAR-13 Species laboratory mouse Generation N15pN1+F2 (16-JAN-13) Generation Definitions   Donating Investigator Dr. 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

Pml^{tm1(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.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Pml^{tm1(PML/RARA)Ley}/Pml⁺ Lyz2^tm1(cre)Ifo/Lyz2⁺

        involves: 129P2/OlaHsd * BALB/cJ * C57BL/6   (conditional)

• tumorigenesis
• leukemia
  • 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)

Pml^{tm1(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)

Pml^{tm1(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)

Pml^{tm1(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 By		Dr. Timothy Ley,   Washington University School of Medicine
Strain of Origin		C57BL/6NTac
Expressed Gene		RARA, retinoic acid receptor, alpha, human
Expressed Gene		PML, promyelocytic leukemia, human
General Note		ES cell line = B6-Blu (C57BL/6)
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

Pml^{tm1(PML/RARA)Ley}, Separated 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]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   12-MAR-13
Diet Information	LabDiet® 5K20

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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'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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