Six2-TGCtg mice harbor an ~181 kb BAC transgene with a Tet-off-eGFPCre under control of the Six2 promoter/enhancer regions within the BAC transgene. The Tet-off-eGFPCre contains both the tetracycline-controlled transactivator protein (tTA) as well as the tetracycline operator (tetO; also called tetracycline-responsive element [TRE] or tet-operator) upstream of an EGFPCre fusion protein, however this strain is not useful as a Tet-Off tool (see below). Tet-independent expression of the eGFPCre fusion protein (EGFP immunofluorescence and direct fluorescence/Cre recombinase activity) is directed to nephron progenitor population cap mesenchyme from the onset of metanephric kidney development. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequence(s) in such tissues of the offspring. These Six2-TGCtg mice may be useful as fluorescent or Cre-lox tools for lineage-tracing/marking Six2-expressing cells for studying multipotent nephron progenitor cell populations throughout kidney organogenesis. Hemizygous Six2-TGCtg mice are viable and fertile. The donating investigator reports they were unable to produce homozygous mice from hemizygous matings. This strain is not useful as a Tet-Off tool [October 2009]: Sequence updates published after this transgene was created revealed an upstream Six2 ATG start site that is in-frame with the tTA; thus an apparent and unintended fusion was created with the tTA (80 amino acids potentially added) that renders transgene expression unaffected by tetracycline/doxycycline administration. It is not known whether the "mutant" tTA is resistant to tetracycline/doxycycline inactivation and still binds to TRE to activate EGFPCre expression or if the TRE acts as a minimal promoter adjacent to the Six2 promoter in the presence of a nonfunctional tTA. Either way, Tet-independent expression of the eGFPCre fusion protein (EGFP immunofluorescence and direct fluorescence/Cre recombinase activity) is directed to nephron progenitor population cap mesenchyme from the onset of metanephric kidney development. Six3 expression from the Six2-TGCtg BAC transgene [February 2023]: The donating investigator reports that while endogenous Six3 is not known to be expressed in the kidney, recently they have discovered these Six2-TGCtg mice exhibit Six3 expression in nephron progenitor cells, presumably from the ~181 kb BAC transgene (which contains the Six3 locus ~70 kb away from the modified Six2 locus on the BAC transgene). Consequently, ectopic SIX3 expression should be expected by researchers using this strain.

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Six2-TGCtg mice express an EGFPCre fusion protein directed to nephron progenitor population cap mesenchyme from the onset of metanephric kidney development by the Six2 (sine oculis-related homeobox 2 homolog (Drosophila)) promoter/enhancer regions within the ~181 kb BAC transgene. These Six2-TGCtg mice may be useful as fluorescent or Cre-lox tools for lineage-tracing/marking Six2-expressing cells for studying multipotent nephron progenitor cell populations throughout kidney organogenesis.
 Six3 expression from the Six2-TGCtg BAC transgene [February 2023]: This strain is reported to exhibit Six3 expression in nephron progenitor cells, presumably from the ~181 kb Six2-TGCtg BAC transgene. See the Detailed Description section for more information.
 This strain is not useful as a Tet-Off tool [October 2009]: Although the Six2-TGCtg BAC transgene contains a Tet-off sequence (tTA and tetO/TRE), this strain has Tet-independent expression of the EGFPCre fusion protein. See the Detailed Description section for more information.
 The donating investigator has also made available Six2 knock-in/knock-out alleles expressing an EGFP/CreERT2 fusion protein (Six2GCE ; Stock No. <a href="https://www.jax.org/strain/009600">009600</a>) and CreERT2 (Six2CE ; Stock No. <a href="https://www.jax.org/strain/032488">032488</a>).

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STOCK Tg(Six2-EGFP/cre)1Amc/J Frozen Embryo