Development of shRNA transgenic mice for preclinical studies of the MKK4 regeneration kinase

The liver harbors a distinct capacity for endogenous regeneration; however, liver regeneration is often impaired in disease and therefore insufficient to compensate for the loss of hepatocytes and organ function. We recently identified MKK4 as a key regulator of liver regeneration by an in vivo RNAi screen. We could show that the knock down of MKK4 in hepatocytes increases their regenerative capacity and robustness. For further investigations we set out to generate shRNA transgenic mouse lines for inducible and reversible gene silencing of MKK4. We used mir30 based MKK4-shRNAs and placed them in the 3' untransla…