We generated an Rbm20^S637A knock-in mouse, mimicking an un-phosphorylatable mutation found in a well-studied case of DCM as well as an Rbm20 knock-out mouse, and confirmed that the serine residue is critical for the splicing regulation by RBM20 in the heart (Sci Rep, 2018, 2020). 

Surprisingly, only the Rbm20^S637A knock-in mouse developed DCM-like phenotypes and fatal arrhythmia (Figure, Sci Rep, 2020). Similar DCM-like phenotypes were also observed in a pig model of DCM caused by another missense mutation in the RSRSP stretch (Nat Med, 2020). 

The knock-in animal models will be excellent new tools to elucidate mechanisms of DCM pathogenesis and to develop effective therapeutics.