We have engineered a mouse mutation that specifically deletes the C-terminal 18 amino acid sequence of the RXRalpha protein. This deletion corresponds to the last helical alpha structure (H12) of the ligand-binding domain (LBD), and includes the core of the Activating Domain of the Activation Function 2 (AF-2 AD core) that is thought to be crucial in mediating ligand-dependent transactivation by RXRalpha. The homozygous mutants (RXRalpha af2(o)), which die during the late fetal period or at birth, exhibit a subset of the abnormalities previously observed in RXRalpha −/− mutants, often with incomplete penetrance. In marked contrast, RXRalpha af2(o)/RXRbeta −/− and RXRalpha af2(o)/RXRbeta −/− /RXRgamma −/− compound mutants display a large array of malformations, which nearly recapitulate the full spectrum of the defects that characterize the fetal vitamin A-deficiency (VAD) syndrome and were previously found in RAR single and compound mutants, as well as in RXRalpha/RAR(alpha, beta or gamma) compound mutants. Analysis of RXRalpha af2(o)/RAR(alpha, beta or gamma) compound mutants also revealed that they exhibit many of the defects observed in the corresponding RXR alpha/RAR compound mutants. Together, these results demonstrate the importance of the integrity of RXR AF-2 for the developmental functions mediated by RAR/RXR heterodimers, and hence suggest that RXR ligand-dependent transactivation is instrumental in retinoid signalling during development.
The RXRalpha ligand-dependent activation function 2 (AF-2) is important for mouse development
- Views Icon Views
- PDF LinkPDF
- Share Icon Share
- Search Site
B. Mascrez, M. Mark, A. Dierich, N.B. Ghyselinck, P. Kastner, P. Chambon; The RXRalpha ligand-dependent activation function 2 (AF-2) is important for mouse development. Development 1 December 1998; 125 (23): 4691–4707. doi: https://doi.org/10.1242/dev.125.23.4691
Download citation file: