Transgenic mice carrying a tetracycline-inducible, truncated transforming growth factor beta receptor (TbetaRII).
The transforming growth factor-betas (TGFbetas) have multiple roles, making genetic analysis of their functions difficult. We therefore developed transgenic mouse lines to disrupt TGFbeta signaling using a mechanism that is inducible, reversible, and cell-type specific. The transgenic mouse lines carry an EGFP-pBi-DeltaTbetaRII construct (PTR). The DeltaTbetaRII element codes for a dominant-negative receptor that is known to disrupt TGFbeta signaling. The DeltaTbetaRII has a c-myc tag. The transgene was silent in the PTR mice, with expression of both EGFP and DeltaTbetaRII occurring when the PTR mice were crossed with mice that express the tetracycline transactivator (CMV-tTA). The expression of EGFP was repressed by the addition of doxycycline to the drinking water of the PTRxCMV-tTA mice. The PTR mice were then crossed with neuron-specific-tTA mice. Expression of the DeltaTbetaRII transgene in these mice led to an upregulation of native TGFbeta receptor expression, suggesting that neurons can modulate their responsiveness to TGFbetas.
Frugier
Tony
T
Neuromuscular Research Group, Department of Anatomy and Structural Biology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand.
Koishi
Kyoko
K
Matthaei
Klaus I
KI
McLennan
Ian S
IS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D013752:Tetracycline / Q000494:pharmacology; D015854:Up-Regulation
D000900:Anti-Bacterial Agents; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D013752:Tetracycline