This knock-out allele of Tbx6 (T-box 6) deletes exons 1, 2 and part 3, resulting in embryonic lethality by E12.5. Homozygous embryos develop randomized left/right axis determination and altered specification of the posterior paraxial tissue, which differentiates into neural tissue. These mice may be useful for studying skeletal development and neural determination.
Dr. Virginia E. Papaioannou, Columbia University
The Tbx6 (T-box 6) gene belongs to a family of transcription factors involved in development and is crucial to specification of the posterior paraxial mesoderm. Tbx6 alleles are associated with human spondylocostal dysostosis and scoliosis. These knock-out mice contain a neomycin cassette that replaces exons 1, 2 and part of 3 representing the initiating methionine and a portion of the T-box, a DNA binding domain. Homozygous embryos develop abnormalities beginning at E8.5; these include: loss of trunk somites, enlarged tail buds, kinked neural tubes, abnormal heart looping, abnormal nodal cilia morphology and motility, randomized embryo turning and multiple vascular abnormalities. Rather than differentiating into somites, posterior paraxial tissue develops into neural tissue forming neural-tube-like structures flanking the axial neural tube. The paraxial tubes exhibit dorsal/ventral patterning and have differentiated motor neurons. Homozygous embryos die by E12.5 due to hemorrhaging. Heterozygotes are viable and fertile with minor skeletal abnormalities. These mice may be useful for studying skeletal development and neural determination.
A targeting vector containing a neomycin cassette in reverse orientation was used to replace exons 1, 2 and part of exon 3. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J females. Offspring were maintained on a segregating background. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Virginia Papaioannou|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Tbx6, T-box 6|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Sequence encompassing all of exons 1 and 2 and a portion of exon 3 was replaced by a neo cassette inserted by homologous recombination. The deleted region encoded the initiator methionine and the DNA-binding domain of the T-box.|
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or B6129SF2/J inbred mice (Stock No. 101045). Homozygotes are not viable.
When using the Tbx6- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #43610 in your Materials and Methods section.