Overview

Also Known As:flatiron, Fpn^ffe

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).

Donating Investigator

Irene E. Zohn, George Washington University School of Medicine

Genetic overview

Genetic Background	Generation

Slc40a1^ffe

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Slc40a1	solute carrier family 40 (iron-regulated transporter), member 1

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Research Applications

Hematological Research
Research Tools
Metabolism Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Development

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).

Control Suggestions

Wild-type from the colony
002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Zohn IE; De Domenico I; Pollock A; Ward DM; Goodman JF; Liang X; Sanchez AJ; Niswander L; Kaplan J. 2007. The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease Blood 109(10):4171-80PubMed: 17289807 MGI: J:118592

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Genetics

Slc40a1^ffe

Allele Symbol: Slc40a1^ffe

Allele Name	flatiron
Allele Type	Chemically induced (ENU)
Allele Synonym(s)	ffe^H32R; Fpn^ffe
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.

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 4

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
Research Tools
- Hematological Research
Metabolism Research
- Hemochromatosis
  - iron metabolism defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Slc40a1^ffe/Slc40a1^ffe
involves: C3H/HeJ * C57BL/6J

embryo phenotype

abnormal neural tube closure
- Background Sensitivity - neural tube closure defects are seen on a mixed background including C3H/HeJ but not in mice crossed onto 129X1/SvJ background

hematopoietic system phenotype

anemia
- severe anemia

homeostasis/metabolism phenotype

edema
- Background Sensitivity - generalized edema is seen on a mixed background including C3H/HeJ but not in mice crossed onto 129X1/SvJ background

mortality/aging

prenatal lethality, complete penetrance
- mid-gestational lethality

nervous system phenotype

abnormal forebrain development
- Background Sensitivity - forebrain truncations are seen on a mixed background including C3H/HeJ but not in mice crossed onto 129X1/SvJ background

abnormal neural tube closure
- Background Sensitivity - neural tube closure defects are seen on a mixed background including C3H/HeJ but not in mice crossed onto 129X1/SvJ background

vision/eye phenotype

microphthalmia
- Background Sensitivity - microphthalmia is seen on a mixed background including C3H/HeJ but not in mice crossed onto 129X1/SvJ background

Genotype: Slc40a1^ffe/Slc40a1^ffe
involves: 129X1/SvJ * C57BL/6J

hematopoietic system phenotype

anemia
- severe anemia

mammalian phenotype

homeostasis/metabolism phenotype
- Background Sensitivity - generalized edema is not seen in mice crossed onto a 129X1/SvJ background, unlike mice on a mixed background including C3H/HeJ

nervous system phenotype
- Background Sensitivity - forebrain truncations are not seen in mice crossed onto a 129X1/SvJ background, unlike mice on a mixed background including C3H/HeJ
- Background Sensitivity - no neural tube defects are seen in mice crossed onto a 129X1/SvJ background, unlike mice on a mixed background including C3H/HeJ

vision/eye phenotype
- Background Sensitivity - microphthalmia is not seen in mice crossed onto a 129X1/SvJ background, unlike mice on a mixed background including C3H/HeJ

mortality/aging

prenatal lethality, complete penetrance
- mid-gestational lethality

Genotype: Slc40a1^ffe/Slc40a1⁺
either: (involves: 129X1/SvJ * C57BL/6J) or (involves: C3H/HeJ * C57BL/6J)

hematopoietic system phenotype

abnormal erythrocyte morphology

abnormal macrophage physiology
- iron loaded macrophages are not able to export iron as efficiently as wild-type cells

anemia
- mild anemia

anisocytosis
- some hypochromic red cells with variable size are present in blood smears

decreased mean corpuscular hemoglobin
- some hypochromic red cells are present in blood smears

leptocytosis
- some target cells are present in blood smears

immune system phenotype

abnormal macrophage physiology
- iron loaded macrophages are not able to export iron as efficiently as wild-type cells

liver/biliary system phenotype

increased liver iron level
- aged mice accumulate high levels of iron in Kupffer cells

homeostasis/metabolism phenotype

increased circulating ferritin level
- serum ferritin levels are increased 10-fold compared to wild-type mice at 6 months of age and levels continue to increase with age

increased circulating unsaturated transferrin level
- at 6 months of age transferrin saturation in serum is much lower than in wild-type mice

increased liver iron level
- aged mice accumulate high levels of iron in Kupffer cells

References

Zohn IE; De Domenico I; Pollock A; Ward DM; Goodman JF; Liang X; Sanchez AJ; Niswander L; Kaplan J. 2007. The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease Blood 109(10):4171-80PubMed: 17289807 MGI: J:118592

Additional - Slc40a1^ffe related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Slc40a1
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the flatiron, Fpn^ffe mouse strain in a publication, please cite the originating article(s) and include JAX stock #029246 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 or wildtype for Slc40a1<ffe>

Related Products and Services

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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Also Known As:flatiron, Fpnffe

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Slc40a1ffe

Allele Symbol: Slc40a1ffe

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: Slc40a1ffe/Slc40a1ffeinvolves: C3H/HeJ * C57BL/6J

embryo phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

mortality/aging

nervous system phenotype

vision/eye phenotype

Genotype: Slc40a1ffe/Slc40a1ffeinvolves: 129X1/SvJ * C57BL/6J

hematopoietic system phenotype

mammalian phenotype

mortality/aging

Genotype: Slc40a1ffe/Slc40a1+either: (involves: 129X1/SvJ * C57BL/6J) or (involves: C3H/HeJ * C57BL/6J)

hematopoietic system phenotype

immune system phenotype

liver/biliary system phenotype

homeostasis/metabolism phenotype

References

Additional - Slc40a1ffe 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

Also Known As:flatiron, Fpn^ffe

Slc40a1^ffe

Allele Symbol: Slc40a1^ffe

Genotype: Slc40a1^ffe/Slc40a1^ffe
involves: C3H/HeJ * C57BL/6J

Genotype: Slc40a1^ffe/Slc40a1^ffe
involves: 129X1/SvJ * C57BL/6J

Genotype: Slc40a1^ffe/Slc40a1⁺
either: (involves: 129X1/SvJ * C57BL/6J) or (involves: C3H/HeJ * C57BL/6J)

Additional - Slc40a1^ffe related