Characterisation of inosine monophosphate dehydrogenase expression during retinal development: Differences between variants and isoforms

Jennifer H. Gunter, Elaine C. Thomas, Nadia Lengefeld, Sarah J. Kruger, Leah Worton, Edith M. Gardiner, Alun Jones, Nigel L. Barnett, Jonathan P. Whitehead*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

Abstract

In mammals there are two ubiquitous, catalytically indistinguishable isoforms of inosine monophosphate dehydrogenase and mutations in the type I isoform, but not type II, cause retina-specific disorders. We have characterised the spatio-temporal expression of these proteins during development of the rat retina and performed functional investigations of the recently described retinal type I variants. Inosine monophosphate dehydrogenase was present in all immature cells throughout the retina during embryonic and neonatal development. Following eye opening and cell differentiation its distribution was restricted to the photoreceptors and bipolar cells, becoming prominent in Müller cells with aging. Type II was present in early, developing retinae whilst type I was undetectable. An isoform switch occurred around P10, after which the type I variants, type Iα and type Iγ, were the major forms. Functional investigations indicate type Iγ has greater catalytic activity compared with other variants and isoforms. Finally, all forms of type I show an increased propensity to form intracellular macrostructures compared to type II and these structures appear to be regulated in response to changing intracellular GTP levels. Collectively these data demonstrate that (i) type I does not play a role in early retinal development, (ii) type Iγ has greater activity and (iii) there are differences between type I and type II isoforms. These observations are consistent with the aetiology of retinitis pigmentosa and raise the possibility that programmed expression of specific inosine monophosphate dehydrogenase proteins may have arisen to meet the requirements of the cellular environment.

Original languageEnglish
Pages (from-to)1716-1728
Number of pages13
JournalInternational Journal of Biochemistry and Cell Biology
Volume40
Issue number9
DOIs
Publication statusPublished - 7 Feb 2008
Externally publishedYes

    Fingerprint

Cite this