Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Reduced levels of gene product (mRNA) is detected by RT-PCR analysis. Mutant mice are thrombocytopenic and anemic at birth. Adult mutant mice have enlarged spleens and exhibit thrombocytopenia due to arrested megakaryocyte maturation which results in increased megakaryocytes in spleen and bone marrow. Platelet number in adult mutant mice is only 10% of wildtype. Erythroblast and mast cell differentiation is defective as indicated by increased apoptotic rates and accumulation of progenitors. Mutant mice display an enhanced response and recovery to experimentally induced acute and chronic erythropoiesis stimulation. At 15 months of age, homozygous female and heterozygous male mutant mice begin to develop idiopathic myelofibrosis-like symptoms including: anemia, tear-drop poikilocytes, progenitor cells in the blood, collagen fibers and osteogenesis in the bone marrow, collagen fibers in the spleen and hematopoietic foci in the liver. This mutant mouse strain may be useful in studies of hematopoiesis.
A targeting vector containing a loxP site flanked neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter and a herpes simplex virus thymidine kinase gene was used to disrupt the I-testes (IT) promoter and Dnase I-hypersensitive (HS) regions of the targeted gene. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. Heterozygous progeny were then interbred to generate mice homozygous for the mutant allele. This line originated from one breeder pair of B6;129S4-Gatatm2Sho mice obtained from Dr. Stuart Orkin. The strain was backcrossed to CD-1 for two generations and is maintained as a homozygote.
|Allele Name||targeted mutation 2, Stuart Orkin|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||GATA-1low; neo deltaHS; neodeltaHS|
|Gene Symbol and Name||Gata1, GATA binding protein 1|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A loxP-flanked neomycin selection cassette replaced the "IT" and DNAseI hypersensitive region of the promoter. RT-PCR experiments demonstrated that this mutation resulted in the loss of expression in megakaryocytes and fetal liver but not in erythroid cells.|
|Mutations Made By|| |
Stuart Orkin, Harvard University
When maintaining a live colony, homozygous mice may be bred together. Maintenance notes suggest 6% grain. The coat color expected from breeding is albino, black.
When using the neoΔHS mouse strain in a publication, please cite the originating article(s) and include JAX stock #004655 in your Materials and Methods section.