3.1.4. Prph2L185P

The substitution of leucine at position 185 to proline (L185P) in Prph2 causes a rare digenic form of RP. Patients heterozygous for both the L185P mutation and a null mutation in Rom1 exhibit symptoms of RP, while carriers of any of the two mutations do not show a phenotype [102,103]. Transgenic mice expressing the L185P mutation in a *Prph2*+/− or a digenic *Prph2*+/−/*Rom1*+/− background displayed a late onset thinning of the outer nuclear layer (ONL) concomitant with reduced scotopic electroretinograms (ERG) [104].

The transgenic mouse models described above provided valuable insights into the pathophysiology of Prph2 related diseases. Since the promoters used to express the transgene are heterologous, often levels of expression of the transgene di ffer considerably from that of the endogenous leading to a varied phenotype.

### *3.2. Prph2 Knockin Mouse Models*

The variation in expression levels of the transgene observed in transgenic mouse models is particularly problematic in cases of reduced levels of the expressed protein since reductions in the expression level of WT Prph2 were shown to result in haploinsu fficiency leading to severe retinal defects [16,105]. Haploinsu fficiency makes it hard to distinguish between the e ffects seen in transgenic mice that are due to the mutation or those resulting from the reduced levels of expressed protein. In order to overcome this, recent studies relied on Prph2 knockin mouse models for a set of mutations found in patients of Prph2 related diseases. Below are the models currently presented in the literature and comparison of their retinal phenotypes to patient's phenotype carrying the same mutation.
