Characterization of retinal inosine monophosphate dehydrogenase 1 in several mammalian species.

Purpose: The purpose of this study was to characterize the inosine monophosphate dehydrogenase 1 (IMPDH1) protein isoforms in mammalian retinas, in order to determine the species distribution of these variants and identify an optimal animal model for studying IMPDH1-associated retinal diseases. Mutations in IMPDH1 cause the RP10 form of autosomal dominant retinitis pigmentosa, and are a rare cause of Leber congenital amaurosis.

Methods: Retinas from several mammalian species were obtained commercially. Human retinas were isolated by the San Diego Eye Bank and flash frozen within four hours post mortem. Proteins were isolated from retinal tissue using the PARIS protocol. Anti-IMPDH1 antibodies were used to visualize the IMDPH1 proteins on Western blots.

Results: Transcript and protein analyses have shown that IMPDH1 undergoes alternate splicing to produce at least two retinal isoforms in both human and mouse. The relative abundance of these IMPDH1 isoforms is different between mouse and human. This study extends these findings by showing that the two IMPDH1 isoforms are also present in dog, rat, sheep, pig, and cow retina, but that, as with mouse, the relative abundances of these isoforms differ from those found in human retina.

Conclusions: The existence of two major retinal isoforms of the IMPDH1 protein is maintained across all mammalian species tested. The relative abundance of IMPDH1 proteins in human retina is unique in comparison to other mammalian species, indicating an apparent lack of an ideal model organism for human retinal IMPDH1 expression. Pig and/or sheep may prove to be potential model organisms based on the observed retinal isoform abundance in these species. These findings will aid future research in understanding the role of retinal-specific IMPDH1 proteins, and will contribute to research elucidating the pathophysiology associated with IMPDH1 missense mutations.