These transgenic mice allow Tet-Off/Tet-On regulated expression of FasL. FasL overexpression leads to Fas/FasL receptor-mediated death-signaling pathway activation and results in cell apoptosis.
Monique E De Paepe, Women and Infants Hospital
Mice hemizygous for the (tetOp)7-FasL transgene (TetOp-FasL transgenic mice) are viable and fertile with no reported phenotypic abnormalities. The (tetOp)7-FasL transgene has the Tet response element (TRE or tetO) upstream of a murine Fas ligand (FasL) coding sequence. When bred with other mice expressing tetracycline-controlled transactivator protein (tTA) or reverse tetracycline-controlled transactivator protein (rtTA), FasL overexpression in the resulting double mutant offspring can be regulated with tetracycline or its analog doxycycline (dox). FasL overexpression leads to Fas/FasL receptor-mediated death-signaling pathway activation and results in cell apoptosis. The donating investigator reports that transgenic mice from founder line B (TetOp-FasL transgenic line B) exhibit very high FasL overexpression levels in the presence of rtTA and 0.01 mg/ml Dox (low FasL levels are achievable by titrating Dox even lower). The donating investigator reports that TetOp-FasL transgenic line B mice exhibit "none-to-very-very-minimal" transgenic FasL expression in the absence of tTA or rtTA+Dox.
Mice harboring the (tetOp)7-FasL transgene allow Tet-Off/Tet-On expression of FasL, and are a tool for temporal regulation of apoptotic cell death in specific tissue/cell types (via inducible FasL overexpression and subsequent activation of the Fas/FasL receptor-mediated death-signaling pathway).
For example, when TetOp-FasL transgenic line B mice are bred to a strain expressing rtTA in developing/adult lung and respiratory epithelium (CCSP-rtTA; Stock No. 006222), the resulting double transgenic mice (CCSP-rtTA/[tetOp]7-FasL) allow dox-inducible FasL-overexpression in respiratory epithelium and are a model for neonatal lung injury and bronchopulmonary dysplasia (BPD). Following dox administration to pregnant or nursing dams, CCSP-rtTA/[tetOp]7-FasL neonatal mice exhibit increased alveolar epithelial apoptosis induced by FasL overexpression that results in BPD-like disrupted alveolar remodeling.
The (tetOp)7-FasL transgene was designed in the laboratory of Dr. Monique E. De Paepe (Women and Infants Hospital, Providence, Rhode Island) with a Tet response element (TRE) upstream of the 943 bp murine Fas ligand (FasL) coding sequence, all followed by a bovine growth hormone intron and polyA sequence. The Tet response element (TRE) contains seven copies of the 42-bp tet operator sequence (tetO) just upstream of a minimal CMV promoter. The 2.9 kbp (tetOp)7-FasL transgene was injected into fertilized FVB/N oocytes. Founder mice from line B were found to contain ~6 copies of the transgene and high levels of doxycycline-induced FasL mRNA up-regulation. These founder mice were bred with FVB/NTac wildtype mice for 12-13 generations prior to sending to The Jackson Laboratory Repository. Upon arrival, TetOp-FasL transgenic line B mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony.
|Expressed Gene||Fasl, Fas ligand (TNF superfamily, member 6), mouse, laboratory|
|Site of Expression|
|Allele Name||transgene insertion B, Monique De Paepe|
|Allele Type||Transgenic (Inducible, Inserted expressed sequence)|
|Allele Synonym(s)||(tetOp)7-FasL transgenic line B; TetOp-FasL transgenic line B|
|Gene Symbol and Name||Tg(tetO-Fasl)BDepa, transgene insertion B, Monique De Paepe|
|Promoter||tetO, tet operator,|
|Expressed Gene||Fasl, Fas ligand (TNF superfamily, member 6), mouse, laboratory|
|Strain of Origin||FVB/N|
|Molecular Note||The (tetO)7-FasL transgene was designed with a Tet response element (TRE) upstream of the 943 bp murine Fas ligand (FasL) coding sequence, all followed by a bovine growth hormone intron and polyA sequence. The Tet response element (TRE) contains seven copies of the 42-bp tet operator sequence (tetO) just upstream of a minimal CMV promoter. Five founder lines (A-E) were established. Founder mice from line B were found with ~6 copies of the transgene and high levels of doxycycline-induced FasL mRNA up-regulation.|
|Mutations Made By|| |
Monique De Paepe, Women and Infants Hospital
When maintaining a live colony, hemizygous mice may be bred to wildtype siblings or to FVB/NJ inbred mice (Stock No. 001800). The donating investigator has not tried to generate homozygous mice.
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