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

Abstract

The transforming growth factor-betas (TGFβs) have multiple roles, making genetic analysis of their functions difficult. We therefore developed transgenic mouse lines to disrupt TGFβ 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 ΔTβRII element codes for a dominant-negative receptor that is known to disrupt TGFβ signaling. The ΔTβRII has a c-myc tag. The transgene was silent in the PTP mice, with expression of both EGFP and ΔTβRII 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 ΔTβRII transgene in these mice led to an upregulation of native TGFβ receptor expression, suggesting that neurons can modulate their responsiveness to TGFβs. © 2005 Wiley-Liss, Inc.