Purchase this article with an account.
C.J. Spellicy, S.J. Bowne, L.S. Sullivan, J. Zhu, Q. Liu, E.A. Pierce, S.P. Daiger; Characterizing Retinal IMPDH1 in Several Mammalian Species . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4901.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study is to identify and characterize a model organism in which to study IMPDH1 in the retina. Mutations in IMPDH1 cause the RP10 form of retinitis pigmentosa (RP), which is typically characterized by a severe, early onset phenotype with rapid disease progression. IMPDH1 catalyzes the rate–limiting step of de novo guanine synthesis, however research has shown that autosomal dominant RP associated mutations in this protein do not alter its enzymatic function.
Human retinas were isolated by the San Diego Eye Bank and placed in RNAlater or flash frozen within four hours of death. Mouse retinas were isolated and also flash frozen. Retinas from several other mammalian species were obtained from Pel–Freez Biologicals. Proteins and RNA were isolated from the retinas using standard methods. Antibodies against IMPDH1 were used to visualize the IMPDH1 proteins on western blots.
Transcript and protein analyses have shown that human IMPDH1 undergoes alternate splicing to produce multiple retinal isoforms, several of which are novel. Western blot analysis suggests that multiple isoforms are also present in mouse, canine, and bovine retina, but that the relative abundance of the isoforms differ from human.
Our analysis of mammalian retinas suggests that human retina has different ratios of the IMPDH1 proteins than any of the mammalian species tested to date. Analysis of additional species is ongoing.
This PDF is available to Subscribers Only