Transgenic mice carrying a tetracycline-inducible, truncated transforming growth factor beta receptor (TβRII)

The transforming growth factor-betas (TGF beta s) have multiple roles, making genetic analysis of their functions difficult. We therefore developed transgenic mouse lines to disrupt TGF beta signaling using a mechanism that is inducible, reversible, and cell-type specific. The transgenic mouse lines carry an EGFP-pBi-DeltaT-betaRII construct (PTR). The Delta T beta RII element codes for a dominant-negative receptor that is known to disrupt TGF beta signaling. The Delta T beta RII has a c-myc tag. The transgene was silent in the PTR mice, with expression of both EGFP and Delta T beta RII 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 Delta T beta RII transgene in these mice led to an upregulation of native TGF beta receptor expression, suggesting that neurons can modulate their responsiveness to TGF beta s. (c) 2005 Wiley-Liss, Inc.