Overview

These Tfr2^Y245X 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 Tfr2^Y245X mutant mice may be useful in studying intestinal iron loading and hemochromatosis type 3.

Donating Investigator

Robert E Fleming, Saint Louis University School of Med

Genetic overview

Genetic Background	Generation

Tfr2^tm1Slu

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Tfr2	transferrin receptor 2

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Research Applications

Hematological Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Metabolism Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These Tfr2^Y245X 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 Tfr2^Y245X 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 Tfr2^Y245X mutant strain was maintained on this mixed genetic background for many generations. Subsequently, these Tfr2^Y245X 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 Suggestions

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

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):10653-8PubMed: 12134060 MGI: J:78360

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Genetics

Tfr2^tm1Slu

Allele Symbol: Tfr2^tm1Slu

Allele Name	targeted mutation 1, St Louis School of Medicine
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	TfR2^245x; Tfr2^Y245X
Gene Symbol and Name	Tfr2, transferrin receptor 2
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	5
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 with cre 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.
Mutations Made By	Timothy Becker, Saint Louis University School of Med

Disease/Phenotype

Disease Terms

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

Research Areas By Phenotype

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
Mouse/Human Gene Homologs
- hemochromatosis

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Tfr2^tm1Slu/Tfr2^tm1Slu
involves: 129X1/SvJ * C57BL/6J

hematopoietic 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)
- little iron is detectable in splenic reticuloendothelial macrophages from homozygous mutant mice, as revealed by Perls' staining

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)
- little iron is detectable in splenic reticuloendothelial macrophages from homozygous mutant mice, as revealed by Perls' staining

liver/biliary system phenotype

increased liver iron level
- Normal - in contrast, kidney iron concentrations remain relatively unaffected
- 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)
- iron deposition in mutant liver tissue is hepatocellular with a marked gradient from periportal to pericentral hepatocytes, as revealed by Perls' Prussian blue staining

mammalian phenotype

hematopoietic system phenotype
- Normal - 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

homeostasis/metabolism 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)
- Normal - in contrast, kidney iron concentrations remain relatively unaffected
- iron deposition in mutant liver tissue is hepatocellular with a marked gradient from periportal to pericentral hepatocytes, as revealed by Perls' Prussian blue staining

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)
- little iron is detectable in splenic reticuloendothelial macrophages from homozygous mutant mice, as revealed by Perls' staining

abnormal iron homeostasis
- homozygotes exhibit abnormalities in iron homeostasis

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)

References

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):10653-8PubMed: 12134060 MGI: J:78360

Additional - Tfr2^tm1Slu related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Trfr2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the FVB.129X1(B6)-Tfr2^tm1Slu/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005215 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

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Live Mouse

Age

Genotype

Price

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Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous for Trfr2<tm1Slu>

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Tfr2tm1Slu

Allele Symbol: Tfr2tm1Slu

Disease Terms

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).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tfr2tm1Slu/Tfr2tm1Sluinvolves: 129X1/SvJ * C57BL/6J

hematopoietic system phenotype

immune system phenotype

liver/biliary system phenotype

mammalian phenotype

homeostasis/metabolism phenotype

References

Additional - Tfr2tm1Slu related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Tfr2^tm1Slu

Allele Symbol: Tfr2^tm1Slu

Genotype: Tfr2^tm1Slu/Tfr2^tm1Slu
involves: 129X1/SvJ * C57BL/6J

Additional - Tfr2^tm1Slu related