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

Authors: Gunter, JH  Thomas, EC  Lengefeld, N  Kruger, SJ  Worton, L  Gardiner, EM  Jones, A  Barnett, NL  Whitehead, JP 
Citation: Gunter JH, etal., Int J Biochem Cell Biol. 2008;40(9):1716-28. Epub 2008 Jan 18.
Pubmed: (View Article at PubMed) PMID:18295529
DOI: Full-text: DOI:10.1016/j.biocel.2007.12.018

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 Muller 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 Ialpha and type Igamma, were the major forms. Functional investigations indicate type Igamma 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 Igamma 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.

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CRRD Object Information
CRRD ID: 5144133
Created: 2011-08-01
Species: All species
Last Modified: 2011-08-01
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.