This application explores the discovery that a circadian clock found in photo receptors is regulated by a mechanism that includes a transcription/translation mechanism and provides output into a number of systems that show rhythmic behavior including transcription of some genes. To explore these observations, there are four specific aims: 1) to clone and characterize rhythmic mRNAs, 2) to analyze the regulation of rhythmic messenger RNAs by light and dopamine to explore their relationship to the clock, 3) to determine if the rhythmic gene products in Xenopus are rhythmically regulated in other vertebrate retinas or other circadian clock systems and 4) to develop a transfectable culture system suitable to study rhythmic gene expression in the retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002414-24
Application #
2888088
Study Section
Special Emphasis Panel (ZRG1-VISB (01))
Project Start
1989-07-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
24
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Besharse, Joseph C; McMahon, Douglas G (2016) The Retina and Other Light-sensitive Ocular Clocks. J Biol Rhythms 31:223-43
Carver, Koryn A; Lourim, David; Tryba, Andrew K et al. (2014) Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature. Am J Physiol Cell Physiol 307:C989-98
Fogerty, Joseph; Besharse, Joseph C (2014) Subretinal infiltration of monocyte derived cells and complement misregulation in mice with AMD-like pathology. Adv Exp Med Biol 801:355-63
Toonen, Joseph; Liang, Lina; Sidjanin, Duska J (2012) Waved with open eyelids 2 (woe2) is a novel spontaneous mouse mutation in the protein phosphatase 1, regulatory (inhibitor) subunit 13 like (Ppp1r13l) gene. BMC Genet 13:76
Scoma, Heather Dehlin; Humby, Monica; Yadav, Geetha et al. (2011) The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light. PLoS One 6:e25382
Fogerty, Joseph; Besharse, Joseph C (2011) 174delG mutation in mouse MFRP causes photoreceptor degeneration and RPE atrophy. Invest Ophthalmol Vis Sci 52:7256-66
Insinna, Christine; Luby-Phelps, Katherine; Link, Brian A et al. (2009) Analysis of IFT kinesins in developing zebrafish cone photoreceptor sensory cilia. Methods Cell Biol 93:219-34
Insinna, Christine; Humby, Monica; Sedmak, Tina et al. (2009) Different roles for KIF17 and kinesin II in photoreceptor development and maintenance. Dev Dyn 238:2211-22
Insinna, Christine; Besharse, Joseph C (2008) Intraflagellar transport and the sensory outer segment of vertebrate photoreceptors. Dev Dyn 237:1982-92
Green, Carla B; Douris, Nicholas; Kojima, Shihoko et al. (2007) Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity. Proc Natl Acad Sci U S A 104:9888-93

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