B6.129S6(Cg)-Ahsp^tm1.1Mjwe/J

Stock number: 007858
Research areas: Developmental Biology Research, Hematological Research, Research Tools

Description

The entire coding region of the erythroid associated factor gene has been disrupted in this mutant mouse line. This gene (also called α-hemoglobin stabilizing protein or AHSP) specifically binds the cytotoxic free α-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.

Detailed 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 α-hemoglobin stabilizing protein specifically binds the cytotoxic free α-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.

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.

Allele

Symbol: Ahsp^tm1.1Mjwe
Name: targeted mutation 1.1, Mitchell J Weiss
MGI accession ID: MGI:3769235
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: AHSP-
Marker symbol: Ahsp
Marker name: alpha hemoglobin stabilizing protein
Marker synonyms: EDRF; Eraf
Chromosome: 7
Strain of origin: 129S6/SvEvTac
Molecular note: A loxP site flanked neomycin resistance gene cassette replaced the entire coding region. 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.