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

View Genetics

Research Applications

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

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

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

View All References

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
- 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

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

abnormal iron homeostasis
- homozygotes exhibit abnormalities in iron homeostasis

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

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)

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

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

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Trfr2<tm1Slu>

Related Products and Services

Frozen Mouse Embryo	FVB.129X1(B6)-Tfr2<tm1Slu>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	FVB.129X1(B6)-Tfr2<tm1Slu>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	FVB.129X1(B6)-Tfr2<tm1Slu>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	FVB.129X1(B6)-Tfr2<tm1Slu>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

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.

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.

Terms Of Use

General Terms and Conditions

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

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tfr2^tm1Slu

Allele Symbol: Tfr2^tm1Slu

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

Additional - Tfr2^tm1Slu related