In this paper, the turbulent mixed convection in a channel flow with differentially heated walls is considered for a fixed Richardson number (Ri(b) = 0.5) and three different Prandtl numbers (Pr = 1, 0.1 and 0.01). Numerical simulations are conducted assuming constant fluid properties and the effect of the buoyancy is taken into account by means of the Boussinesq approximation. Direct Numerical Simulations (DNS) are performed first and the effect of the buoyancy on the first and second order statistics of the fluid and thermal fields is highlighted. Furthermore, it is found that in mixed convection the Prandtl number has a much larger effect on the results than in the case of forced convection. The obtained DNS results are then used as a validation database for two different RANS turbulent heat flux models, i.e. the classical Reynolds analogy and a recently proposed three-equation algebraic heat flux models called AHFM-NRG+. It is observed that, as expected, the Reynolds analogy fails to predict the thermal field even for unitary Prandtl numbers fluids. On the other hand, it is shown that the AHFM-NRG+ is in a reasonable agreement with the reference DNS over the entire range of Prandtl numbers considered in the study. (C) 2018 Elsevier Ltd. All rights reserved.