Strain Name:

FVB.129X1(B6)-Tfr2tm1Slu/J

Stock Number:

005215

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Availability:

Cryopreserved - Ready for recovery

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These Tfr2Y245X mutant mice have codon 245 of the targeted gene converted to a stop codon; this mutation corresponds to the human truncation mutation Y250X which is the cause of hemochromatosis (HH type 3). As such, these Tfr2Y245X mutant mice may be useful in studying intestinal iron loading and hemochromatosis type 3.

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 FVB.129X1(B6)-Trfr2tm1Slu/J    (Changed: 04-JUN-12 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Robert E Fleming,   Saint Louis University School of Med

Description
These Tfr2Y245X mice have codon 245 of the targeted gene converted to a stop codon; this mutation corresponds to the human truncation mutation Y250X which is the cause of hemochromatosis (HH type 3). Mice that are homozygous for the targeted mutation are viable and fertile. Northern blot analysis of total RNA from liver tissue detects a reduced level of full length gene product (mRNA). PCR analysis of liver tissue detects the C to G point mutation in exon 6. Western blot analysis of hepatic membrane preparations does not detect truncated gene product (protein). By 4 weeks of age, homozygotes display ~5-fold increase in liver iron levels and ~1.5-fold increase in serum transferrin saturations levels over wildtype control. Iron deposition in the liver is hepatocellular and periportal. Mice homozygous for the mutation have decreased iron concentrations in the spleen, indicating reticuloendothelial iron sparing. These Tfr2Y245X mutant mice may be useful in studying intestinal iron loading and hemochromatosis type 3.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector was designed to disrupt exon 6 and intron 6 of the targeted gene with a C to G point mutation at codon 245 (Y245X) in exon 6 and a loxP site flanked self-deleting selection cassette (containing a neomycin resistance gene and Cre recombinase under the control of a testes-specific angiotensin-converting enzyme promoter). The construct was electroporated into 129X1/SvJ derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts, and chimeric males were crossed to C57BL/6J females. The resulting mutant offspring (with the selection cassette excised following cre expression in the germ line of the chimeric males) were established. The Tfr2Y245X mutant strain was maintained on this mixed genetic background for many generations. Subsequently, these Tfr2Y245X mutant mice were backcrossed to FVB/N inbred mice for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony.

Control Information

  Control
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Hemochromatosis, Type 3; HFE3
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tfr2tm1Slu/Tfr2tm1Slu

        involves: 129X1/SvJ * C57BL/6J
  • homeostasis/metabolism phenotype
  • abnormal iron homeostasis
    • homozygotes exhibit abnormalities in iron homeostasis   (MGI Ref ID J:78360)
    • decreased spleen iron level
      • at 4 weeks of age, homozygotes maintained on a standard diet show significantly reduced splenic iron concentrations (239 +/- 13 ug/g) relative to wild-type (490 +/- 75 ug/g) and heterozygous control mice (451 +/- 30 ug/g)   (MGI Ref ID J:78360)
      • little iron is detectable in splenic reticuloendothelial macrophages from homozygous mutant mice, as revealed by Perls' staining   (MGI Ref ID J:78360)
    • increased circulating iron level
      • at 4 weeks of age, homozygotes maintained on a standard diet display significantly increased transferrin saturations (88.9 +/- 5.3 ug/g) relative to wild-type (56.2 +/- 5.3 ug/g) and heterozygous control mice (57 +/- 7.8 ug/g)   (MGI Ref ID J:78360)
    • increased liver iron level
      • at 4 weeks of age, homozygotes maintained on a standard diet show significantly increased liver iron concentrations (1916 +/- 145 ug/g) relative to wild-type (382 +/- 43 ug/g) and heterozygous control mice (460 +/- 46 ug/g)   (MGI Ref ID J:78360)
      • iron deposition in mutant liver tissue is hepatocellular with a marked gradient from periportal to pericentral hepatocytes, as revealed by Perls' Prussian blue staining   (MGI Ref ID J:78360)
      • in contrast, kidney iron concentrations remain relatively unaffected   (MGI Ref ID J:78360)
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype
    • at 4 weeks of age, homozygotes show normal erythrocyte production, with no significant differences in hemoglobin levels, hematocrits, mean corpuscular volumes, or reticulocyte counts relative to wild-type and heterozygous control mice   (MGI Ref ID J:78360)
    • decreased spleen iron level
      • at 4 weeks of age, homozygotes maintained on a standard diet show significantly reduced splenic iron concentrations (239 +/- 13 ug/g) relative to wild-type (490 +/- 75 ug/g) and heterozygous control mice (451 +/- 30 ug/g)   (MGI Ref ID J:78360)
      • little iron is detectable in splenic reticuloendothelial macrophages from homozygous mutant mice, as revealed by Perls' staining   (MGI Ref ID J:78360)
  • immune system phenotype
  • decreased spleen iron level
    • at 4 weeks of age, homozygotes maintained on a standard diet show significantly reduced splenic iron concentrations (239 +/- 13 ug/g) relative to wild-type (490 +/- 75 ug/g) and heterozygous control mice (451 +/- 30 ug/g)   (MGI Ref ID J:78360)
    • little iron is detectable in splenic reticuloendothelial macrophages from homozygous mutant mice, as revealed by Perls' staining   (MGI Ref ID J:78360)
  • liver/biliary system phenotype
  • increased liver iron level
    • at 4 weeks of age, homozygotes maintained on a standard diet show significantly increased liver iron concentrations (1916 +/- 145 ug/g) relative to wild-type (382 +/- 43 ug/g) and heterozygous control mice (460 +/- 46 ug/g)   (MGI Ref ID J:78360)
    • iron deposition in mutant liver tissue is hepatocellular with a marked gradient from periportal to pericentral hepatocytes, as revealed by Perls' Prussian blue staining   (MGI Ref ID J:78360)
    • in contrast, kidney iron concentrations remain relatively unaffected   (MGI Ref ID J:78360)
View Research Applications

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

Hematological Research
Anemia, Iron Deficiency and Transport Defects
      hemochromatosis

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      MHC class I deficiency, hemochromatosis

Internal/Organ Research
Liver Defects
      hemochromatosis

Metabolism Research
Hemochromatosis
      iron metabolism defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tfr2tm1Slu
Allele Name targeted mutation 1, St Louis School of Medicine
Allele Type Targeted (Null/Knockout)
Common Name(s) TfR2245x; Tfr2Y245X;
Mutation Made By Timothy Becker,   Saint Louis University School of Med
Strain of Origin129X1/SvJ
ES Cell Line NameRW-4
ES Cell Line Strain129X1/SvJ
Gene Symbol and Name Tfr2, transferrin receptor 2
Chromosome 5
Gene Common Name(s) HFE3; TFRC2; Trfr2;
Molecular Note A construct containing a nonsense mutation at codon 245 (in exon 6 and orthologous to human position 250) and a floxed neo cassette in intron 6 was incorporated at the endogenous locus via homologous recombination. Transient transfection of ES cells withcre excised the neo cassette, leaving a single loxP site. Northern blot analysis of total hepatic RNA showed a reduced abundance of normal size transcript in homozygous mutant mice, putatively due to nonsense-mediated decay. Encoded protein was undetected by Western blot analysis. [MGI Ref ID J:78360]

Genotyping

Genotyping Information

Genotyping Protocols

Trfr2tm1Slu, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fleming RE; Ahmann JR; Migas MC; Waheed A; Koeffler HP; Kawabata H; Britton RS; Bacon BR; Sly WS. 2002. Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc Natl Acad Sci U S A 99(16):10653-8. [PubMed: 12134060]  [MGI Ref ID J:78360]

Additional References

Tfr2tm1Slu related

Acikyol B; Graham RM; Trinder D; House MJ; Olynyk JK; Scott RJ; Milward EA; Johnstone DM. 2013. Brain transcriptome perturbations in the transferrin receptor 2 mutant mouse support the case for brain changes in iron loading disorders, including effects relating to long-term depression and long-term potentiation. Neuroscience 235:119-28. [PubMed: 23333676]  [MGI Ref ID J:201382]

Drake SF; Morgan EH; Herbison CE; Delima R; Graham RM; Chua AC; Leedman PJ; Fleming RE; Bacon BR; Olynyk JK; Trinder D. 2007. Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3. Am J Physiol Gastrointest Liver Physiol 292(1):G323-8. [PubMed: 16935854]  [MGI Ref ID J:120595]

Gao J; Chen J; De Domenico I; Koeller DM; Harding CO; Fleming RE; Koeberl DD; Enns CA. 2010. Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice. Blood 115(16):3374-81. [PubMed: 20177050]  [MGI Ref ID J:160786]

Kautz L; Jung G; Valore EV; Rivella S; Nemeth E; Ganz T. 2014. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 46(7):678-84. [PubMed: 24880340]  [MGI Ref ID J:211331]

Kawabata H; Fleming RE; Gui D; Moon SY; Saitoh T; O'Kelly J; Umehara Y; Wano Y; Said JW; Koeffler HP. 2005. Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood 105(1):376-81. [PubMed: 15345587]  [MGI Ref ID J:96512]

Lee P; Peng H; Gelbart T; Beutler E. 2004. The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes. Proc Natl Acad Sci U S A 101(25):9263-5. [PubMed: 15192150]  [MGI Ref ID J:91441]

Lee P; Peng H; Gelbart T; Wang L; Beutler E. 2005. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci U S A 102(6):1906-10. [PubMed: 15684062]  [MGI Ref ID J:96470]

Tjalsma H; Laarakkers CM; van Swelm RP; Theurl M; Theurl I; Kemna EH; van der Burgt YE; Venselaar H; Dutilh BE; Russel FG; Weiss G; Masereeuw R; Fleming RE; Swinkels DW. 2011. Mass spectrometry analysis of hepcidin peptides in experimental mouse models. PLoS One 6(3):e16762. [PubMed: 21408141]  [MGI Ref ID J:171711]

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 may be bred together.

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 willfulfill 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 willfulfill 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
   001800 FVB/NJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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