This strain conditionally-expresses a TEL-AML1 (Etv6-RUNX1, t12;21) translocation/fusion protein associated with childhood acute lymphoblastic leukemia.
Hanno R Hock, Massachusetts General Hospital
The TEL-AML1 (ETV6-RUNX1, t12;21) translocation/fusion protein is a feature in approximately 25% of childhood Acute Lymphoblastic Leukemia (ALL) cases. This leukemia type is initiated in utero, and fusion protein is detectable in cord blood, but overt symptoms don't appear until the third or fourth year of life.
This mutant mouse strain carries a conditional gene fusion created by targeting truncated human RUNX1 (runt related transcription factor 1) cDNA preceded by a loxP-flanked STOP to the first base pair of exon 6 of the mouse Etv6 (ets variant gene 6 (TEL oncogene)) gene. As in leukemic cells, the Etv6 promoter drives expression. After cell or tissue-specific cre-mediated excision of the floxed stop cassette, normal splicing generates an mRNA encoding a hybrid protein with a breakpoint identical to that found in translocation t(12;21). Heterozygous floxed STOP mice are viable, but homozygotes are embryonic lethal due to a loss of Etv6 expression. This strain may be useful in studies of the pre-leukemic phase of childhood Acute Lymphoblastic Leukemia.
When bred to a strain expressing interferon-inducible Cre recombinase (see Stock No. 003556 for example), this mutant mouse strain may be useful in studies of hematopoietic stem cells and leukemia.
Truncated human RUNX1 cDNA preceded by a loxP-flanked neomycin cassette and a loxP-flanked STOP was introduced to the first base pair of exon 6 of the mouse Etv6 gene. Exons 6 and 7 were deleted. The targeting vector was injected into 129S1/Sv-Oca+ Tyr+ Kitl+-derived CJ7 embryonic stem (ES) cells. This donating investigator reported that these mice were backcrossed 8 times to C57BL/6J (see SNP note below).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Hanno Hock|
|Allele Type||Targeted (Conditional ready (e.g. floxed), Humanized sequence, No functional change)|
|Gene Symbol and Name||Etv6, ets variant 6|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||Exons 6 and 7 were replaced with a floxed neo, floxed STOP, and human RUNX1 coding region. When the floxed neo and STOP cassette are removed by cre-mediated recombination, a fusion product of mouse Etv6 and human RUNX1 (or TEL-AML1) was created.|
|Mutations Made By|| |
Hanno Hock, Massachusetts General Hospital
Heterozygous males or females may be bred with wildtype mice to maintain a live colony. Homozygotes are not viable.
When using the B6.129S1-Etv6tm1(RUNX1)Haho/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #016834 in your Materials and Methods section.