FVB/N-Tg(tetO-SOX9)1Xy/J

Stock number: 033449
Product name: TetO-SOX9
Research areas: Research Tools

Description

TetO-SOX9 mice express a flag-tagged human SRY (sex determining region Y)-box 9 (SOX9) cDNA under direction of the tetracycline operator (tetO) integrated on the X Chromosome. When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of SOX9 protein may be regulated with the tetracycline analog doxycycline (dox) in the double mutant offspring. These mice may be useful when studying the role of SOX9 in cell proliferation and differentiation.

Detailed description

TetO-SOX9 mice express a flag-tagged human SRY (sex determining region Y)-box 9 (SOX9) cDNA under direction of the tetracycline operator (tetO) integrated on the X Chromosome. SOX9 is a key mediator of fate determination in developmental processes. As a transcription factor, SOX9 is important in chondrogenesis and skeletal development as well as in sex determination. SOX9 mutations are associated with the human autosomal dominant disease campomelic dysplasia, which is characterized by extreme cartilage and bone malformation, frequent sex reversal, and multiple defects in other organs. It is expressed by most aggressive basal-like breast cancer (BL-BCa) subtypes, and its expression correlates with indicators of poor prognosis. Homozygous females and hemizygous males are viable and fertile. When bred with another mouse expressing tetracycline-controlled transactivator protein (tTA) or reverse tetracycline-controlled transactivator protein (rtTA), tissue specific SOX9 expression in the resulting double mutant offspring can be regulated with tetracycline or its analog doxycycline (dox).

When bred to MMTV-tTA mice to overexpress SOX9 in mammary epithelium, doxycycline-inducible expression of SOX9 results in an increase in LRP6 and TCF4 levels and in cytoplasmic and nuclear β-catenin staining, which are components of the canonical Wnt/β-catenin pathway, indicative of increased cell proliferation and differentiation.

Development

A 1.8kb transgenic construct was designed to contain a flag-tagged human SRY (sex determining region Y)-box 9 (SOX9) cDNA and a SV40 polyadenylation signal driven by the tetracycline operator (tetO). The linearized construct was microinjected into fertilized FVB/NCrl oocytes. TetO-SOX9 founder mice, with the transgene integrated on the X chromosome, were bred to FVB/NCrl mice for at least four generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes (Stock No. 001800).

Allele

Symbol: Tg(tetO-SOX9)1Xy
Name: transgene insertion 1, Xin Yuan
MGI accession ID: MGI:6315862
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(tetO-SOX9)1Xy
Marker name: transgene insertion 1,Xin Yuan
Chromosome: X
Strain of origin: FVB/NCrl
Molecular note: The 1.8kb transgenic construct contains a FLAG-tagged human Sox9 cDNA and an SV40 polyadenylation signal driven by the tetracycline operator (tetO). The transgene inserted on the X chromosome.