3.1.3. Prph2P216L

A substitution of a proline at position 216 in Prph2 with a leucine (P216L) was found to cause RP in patients [101]. Expression of P216L in mice in presence of WT Prph2 (*Prph2*+/+) levels led to an age-dependent significant decrease in scotopic responses and shortened rod OSs with normal disc alignments, indicative of a dominant-gain-of-function effect [84]. Moreover, in the presence of one

WT allele of *Prph2* (*Prph2*+/−), expression of the P216L caused a significant decrease in rod function compared to *Prph2*+/− mice. In these mice, a more severe OS shortening and disorganization of the discs could be observed in presence of the P216L mutant protein. Interestingly, expression of the P216L protein in a *Prph2*−/− retina caused the formation of small, highly ROS, which represents a limited rescue when compared to the complete absence of ROS in *Prph2*−/<sup>−</sup>*.* Taken together, these results prove that the P216L mutation in Prph2 results in a dominant-gain-of e ffect, in agreemen<sup>t</sup> with the rod dominant phenotype observed in patients.
