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.
Robert E Fleming, Saint Louis University School of Med
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Tfr2 | transferrin receptor 2 |
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.
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.
Allele Name | targeted mutation 1, St Louis School of Medicine |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | TfR2245x; Tfr2Y245X |
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 |
When maintaining a live colony, homozygous mice may be bred together.
When using the FVB.129X1(B6)-Tfr2tm1Slu/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005215 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Trfr2<tm1Slu> |
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 |
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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. 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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