B6.129S-Runx1^tm1Spe/J

Stock number: 005669
Product name: Cbfa2 KO
Research areas: Cardiovascular Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These Runx1 knock-out mice exhibit an embryonic lethal phenotype with extensive hemorrhagic lesions in the central nervous system. They are suitable for use in applications related to the study of leukemia.

Detailed description

Heterozygous mice are viable, fertile, devoid of hemorrhagic lesions, and exhibit mild hematopoietic impairment. Mice that are homozygous for the targeted mutation have an embryonic lethal phenotype; animals are alive at embryonic day 11.5, but start dying at embryonic day 12.5. Embryos exhibit extensive hemorrhagic lesions in the central nervous system including the intraventricular regions and metencephalon as well as segmental bleeds at the VII-VIII cranial nerve complex, cervical, thoracic, and caudal regions. At embryonic day 10.5, symmetrical and bilateral necrosis preceding hemorrhage is observed in homozygotes. Homozygous disruption of the endogenous gene completely blocks definitive erythropoiesis, myelopoiesis, and lymphopoiesis. This mutant may be useful in leukemia studies as disruption of the human homolog of this gene is associated with many different leukemias.

Development

A targeting vector containing a phosphoglycerol kinase-driven neomycin resistance gene disrupted the 3.2 kb region coding for amino acids 143-178 (the final 35 amino acids in the DNA binding domain) of the endogenous gene. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were backcrossed to C57BL/6J females. Heterozygotes were backcrossed to (129S1/SvImJ x C57BL/6J)F1 mice for more than 10 generations and then backcrossed to C57BL/6J for at least five more generations.

Allele

Symbol: Runx1^tm1Spe
Name: targeted mutation 1, Nancy A Speck
MGI accession ID: MGI:1857568
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Runx1
Marker name: runt related transcription factor 1
Chromosome: 16
Strain of origin: 129S4/SvJae
Molecular note: Exon 4, which encodes a portion of the DNA-binding domain, was replaced with a PGK-neo cassette. RT-PCR analysis showed a lack of normal transcript in homozygous mutant mice.