This ENU-generated flatiron (ffe) mutation of Slc40a1 creates a missense mutant allele that results in mislocalization of the encoded iron transporter. These mice may be suitable as a model Hemochromatosis Type IV (or Ferroportin Disease).
Irene E. Zohn, George Washington University School of Medicine
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Chemically induced (ENU) | Slc40a1 | solute carrier family 40 (iron-regulated transporter), member 1 |
The targeted Slc40a1 gene encodes the iron transporter ferroportin. Missense mutations in this gene have been associated with hemochromatosis type 4. These ENU-generated flatiron (ffe) Slc40a1 mutants carry a missense A>G nucleotide substitution at position 95 in the coding sequence, resulting in an H32R substitution in the signal sequence. The H32R amino acid substitution results in mislocalization of the ferroportin protein and acts as a dominant negative.
Heterozygotes are viable and fertile. Homozygotes on the 129S1/SvImJ background have a mid-gestational lethal phenotype and severe anemia. 6 month old heterozygotes exhibit mild anemia, low transferrin saturation, high
serum ferritin (10 fold at 6 months of age that increases with age), and excessive iron accumulation in Kupffer cells. Macrophages isolated from heterozygous mice exhibit impaired iron export.
During backcrossing, the Y chromosome may not have been fixed to the 129S1/SvImJ genetic background.
Male C57BL/6J mice were treated with N-ethyl-N-nitrosourea (ENU) and then bred to C3H females. The resulting F1 males were crossed to C3H females, and female offspring mated back to F1 males to homozygose any deleterious mutations. A mutagenesis screen was then performed to select mice with mutations effecting neural tube morphology at embryonic day 12.5.
Following establishment of the line, the genetic mutation was identified by positional cloning followed by sequencing of candidate genes. Sequencing of solute carrier family 40 (iron-regulated transporter), member 1 (Slc40a1) gene identified a A>G nucleotide substitution at position 95 in the coding sequence, resulting in an
H32R substitution in the signal sequence.
The donating investigator reported that these mice were backcrossed to 129S1/SvImJ mice for at least 10 generations. During backcrossing, the Y chromosome may not have been fixed to the 129S1/SvImJ genetic background.
Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize 129S1/SvImJ oocytes (Stock No. 002448).
Allele Name | flatiron |
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Allele Type | Chemically induced (ENU) |
Allele Synonym(s) | ffeH32R; Fpnffe |
Gene Symbol and Name | Slc40a1, solute carrier family 40 (iron-regulated transporter), member 1 |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 1 |
Molecular Note | This allele contains an A to G transition at position 95 in the coding sequence, resulting in an H32R substitution in the signal sequence. |
When maintaining a live colony, heterozygous mice may be bred to wildtype siblings, or to 129S1/SvImJ inbred mice (Stock No. 002448). Homozygotes on the 129S1/SvImJ background have a mid-gestational lethal phenotype.
When using the flatiron, Fpnffe mouse strain in a publication, please cite the originating article(s) and include JAX stock #029246 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Slc40a1<ffe> |
Frozen Mouse Embryo | 129S1.B6(C3)-Slc40a1<ffe>/ZohnJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | 129S1.B6(C3)-Slc40a1<ffe>/ZohnJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | 129S1.B6(C3)-Slc40a1<ffe>/ZohnJ Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | 129S1.B6(C3)-Slc40a1<ffe>/ZohnJ 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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