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General Terms and Conditions

Former Name	B6.129S6-Eraftm1Mjwe/J    (Changed: 05-FEB-08 )
Genes & Alleles	Eraf;   Eraftm1.1Mjwe;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Species laboratory mouse Donating Investigator Mitchell Weiss,   Children's Hospital of Philadelphia

Strain Description
Mice homozygous for this targeted allele (AHSP^-/- or ERAF^-/-) are fertile with normal lifespans up to at least 18 months of age. No RNA or protein from the targeted gene is detected in hematopoietic tissues from homozygotes. AHSP^-/- mice exhibit abnormal erythrocyte morphology with intracellular inclusion bodies that stain positively for denatured hemoglobin (Heinz bodies). Homozygous mice also have reduced lifespan of circulating red blood cells, increased apoptosis of erythroid precursors, and increased production of reactive oxygen species (ROS) with consequent damage to hemoglobin A and other cellular components. As the a-hemoglobin stabilizing protein specifically binds the cytotoxic free a-Hb subunit of hemoglobin A, these AHSP-mutant mice may be useful in studying erythroid development/erythropoiesis, thalassemia, Heinz body hemolytic anemia, and other hemoglobinopathies.

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. As AHSP-mutant mice were originally described on a mixed C57BL/6 and 129 genetic background, 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.

Strain Development
A targeting vector designed to replace the entire coding sequence of the targeted gene with a loxP-flanked pgk-neo cassette was electroporated into 129S6/SvEvTac-derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimera's were bred with C57BL/6 mice to produce heterozygous mutants. Mice were then bred to mice with cre expression in sperm (undetermined genetic background) to remove the neo cassette. The resulting offspring (with a single loxP site replacing the entire coding region) were selected. This mutant strain was then backcrossed to C57BL/6 bred for at least 9 generations prior to arrival at The Jackson Laboratory.

Mammalian Phenotype Terms assigned by genotype The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Eraftm1.1Mjwe/Eraf+         involves: 129S6/SvEvTac * C57BL/6 hematopoietic system phenotype abnormal erythrocyte morphology (MGI Ref ID J:94421) erythrocytes also contain inclusion bodies composed of denatured hemoglobin chains (Heinz bodies) Eraftm1.1Mjwe/Eraftm1.1Mjwe         involves: 129S6/SvEvTac * C57BL/6 hematopoietic system phenotype abnormal hematopoiesis (MGI Ref ID J:94421) there is an elevated level of apoptotic erythroid precursors in mutant spleens abnormal erythrocyte morphology (MGI Ref ID J:94421) target cells (codocytes) and spiculated cells can be seen in blood smears some erythrocytes have inclusion bodies composed of denatured hemoglobin chains (Heinz bodies) erythrocytes exhibit a half-life of 12 days, compared to 22 days of cells from wild-type littermates erythroid precursors show significant hyperplasia in the spleen and to a lesser degree in the bone marrow anisopoikilocytosis (MGI Ref ID J:94421) blood smears show morphologic abnormalities such as irregular size and shape anisocytosis (MGI Ref ID J:94421) significant variation in size of erythrocytes as shown by increased red blood cell distribution width (RBW) decreased mean corpuscular volume (MGI Ref ID J:94421) mice have small red blood cells with low mean corpuscular hemoglobin (13.6 pg vs 16.2 pg in wild-type) polychromatophilia (MGI Ref ID J:94421) large inclusions are present only in polychromatophilic cells, suggesting accelerated erythrocyte destruction anemia (MGI Ref ID J:94421) mice show mild anemia associated with small red blood cells decreased hematocrit (MGI Ref ID J:94421) hematocrit is reduced to 48.7% from 55.8% in wild-type hemoglobin abnormalities (MGI Ref ID J:94421) variation in hemoglobin content of mutant erythrocytes, evidenced by increased hemoglobin distribution width (HDW), is observed erythrocytes contain alpha- and beta-globin precipitates; membrane-associated globin chains are not observed in control littermates abnormal hemoglobin content (MGI Ref ID J:94421) decreased mean corpuscular hemoglobin (MGI Ref ID J:94421) increased erythroid progenitor cell number (MGI Ref ID J:94421) spleen shows increased proportion of erythroid precursors cultured spleen cells show a higher proportion of burst-forming unit erythroid and colony-forming unit erythroid cells (BFUe and CFUe's) reticulocytosis (MGI Ref ID J:94421) reticulocyte count is elevated (to 4.4% from 2.2% in wild-type) enlarged spleen (MGI Ref ID J:94421) spleen is significantly enlarged cellular phenotype increased cellular sensitivity to oxidative stress (MGI Ref ID J:94421) mutants show a larger decrease in hematocrit after phenylhydrazine treatment resulting from hemolytic anemia compared to control littermates oxidative stress (MGI Ref ID J:94421) mutant erythrocytes display intrinsically elevated oxidative stress mice have increased levels of reactive oxygen species catalyzed by alpha-hemoglobin immune system phenotype enlarged spleen (MGI Ref ID J:94421) spleen is significantly enlarged

Gene & Allele Details

Allele Symbol		Eraftm1.1Mjwe
Allele Name		targeted mutation 1.1, Mitchell J Weiss
Common Name(s)		AHSP-/-;
Mutation Made By		Mitchell Weiss,   Children's Hospital of Philadelphia
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TL1/TL-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Eraf, erythroid associated factor
Chromosome		UN
Gene Common Name(s)		AHSP; EDRF;
Molecular Note		A targeting vector was designed to replace the entire coding sequence of the targeted gene with a loxP-flanked pgk-neo cassette. Mice were then bred to spermadine-cre mice to remove the neo cassette. The resulting offspring have a single loxP site replacing the entire coding region. [MGI Ref ID J:77038] [MGI Ref ID J:94421]

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Genotyping Protocols

Eraf^tm1.1Mjwe

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.

Additional Web Information

Congenic Nomenclature

Research Applications

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

Developmental Biology Research
Lymphoid Tissue Defects (hematopoietic defects)

Hematological Research
Anemia, Iron Deficiency and Transport Defects
Anemia, Iron Homeostasis Defects
Hematopoietic Defects
Hemoglobin Defects (beta^O-thalassemia)
Hemoglobin Defects (thalassemia)

Research Tools
Hematological Research

References

Selected Reference(s)

Kihm AJ; Kong Y; Hong W; Russell JE; Rouda S; Adachi K; Simon MC; Blobel GA; Weiss MJ. 2002. An abundant erythroid protein that stabilizes free alpha-haemoglobin. Nature 417(6890):758-63. [PubMed: 12066189]  [MGI Ref ID J:77038]

Kong Y; Zhou S; Kihm AJ; Katein AM; Yu X; Gell DA; Mackay JP; Adachi K; Foster-Brown L; Louden CS; Gow AJ; Weiss MJ. 2004. Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia. J Clin Invest 114(10):1457-66. [PubMed: 15545996]  [MGI Ref ID J:94421]

Yu X; Kong Y; Dore LC; Abdulmalik O; Katein AM; Zhou S; Choi JK; Gell D; Mackay JP; Gow AJ; Weiss MJ. 2007. An erythroid chaperone that facilitates folding of alpha-globin subunits for hemoglobin synthesis. J Clin Invest 117(7):1856-65. [PubMed: 17607360]  [MGI Ref ID J:124209]

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Price and Supply Information

Strain Name:	B6.129S6(Cg)-Eraftm1.1Mjwe/J
Stock Number:	007858

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

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Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below
Control Information	View Control Information in Strain Details.

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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.

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