These Taspase1-/- mice lack exon 9 of the taspase 1, threonine aspartase 1 (Tasp1) gene, abolishing gene function. Taspase1 is an endopeptidase that cleaves mixed-lineage leukemia (MLL) for proper
Homeobox (Hox) gene expression. MLL is a methyltransferase required for sustaining the expression of genes early in embryogenesis. Taspase1 is also required for craniofacial development, fetal hematopoiesis, and has been found overexpressed in some cancer cell lines. Homozygotes are runted and are born at 89% of the expected Mendelian ratio with only 13% surviving to 3 weeks of age due to a feeding defect. They exhibit homeotic transformations in axial skeleton, abnormal craniofacial development, and abnormal outgrowth of cranial nerves. They also show a reduction in hematopoietic stem cell populations and thymocytes. Embryonic fibroblasts (MEFs) exhibit impaired proliferation. Heterozygous Taspase1+/- mice display an intermediate skeletal phenotype.
A targeting vector was designed to insert a single loxP site upstream of exon 9, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 9 of the taspase, threonine aspartase 1 (Tasp1) gene. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a CMV-Cre expression plasmid. Resulting ES cells contained multiple gene rearrangments; intact floxed-exon 9, intact floxed-neo cassette, or excision of both exon 9 and the neo cassette. Correctly targeted ES cells, lacking both exon 9 and the neo, were injected into C57BL/6 blastocysts and resulting chimeric males were bred with C57BL/6 females. Resulting offspring were bred to C57BL/6 mice for at least 6 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1.1, James J Hsieh|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Tasp1, taspase, threonine aspartase 1|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A loxP site was inserted upstream of exon 9 and a floxed PGK neo cassette was inserted into intron 9. Successfully targeted ES cells were subsequently transiently transfected with CMV-cre to excise both exon9 9 and the PGKneo. Protein was not detected in mutant MEFs.|
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664).
When using the B6.129X1-Tasp1tm1.1Jjdh/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021298 in your Materials and Methods section.