3.1.2. Prph2C214S

The substitution of a cysteine at position 214 in Prph2 with a serine (C214S) was shown to cause ADRP, a degeneration of rods followed by a late-onset degeneration of cones [100]. Expression of the C214S transgene in the presence of the full complement of WT Prph2 mice failed to produce any phenotype, proving that the phenotype observed in patients is through a mechanism other than dominant gain-of-function [85]. However, when expressed in *Prph2*+/− or *Prph2*−/− retinas, the C214S protein failed to rescue the functional and structural phenotypes in both rods and cones, indicating that the C214S mutation is resulting in a loss of function. An interesting finding was that the C214S mutant Prph2 was unable to interact with Rom1, indicating an alteration in the formation of complexes caused by this mutation. Although an ample amount of Prph2 C214S transgene message was detected, only a trace amount of the mutant protein was identified, which led to the conclusion of a loss-of-function phenotype associated with the C214S mutation. It is unclear whether the low levels of mutant protein are due to a low rate of synthesis or instability of the mutant protein.
