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The role of circadian clock genes in the eye: a shift in scientific focus

Objetivo

The mammalian circadian system controls daily cycles in sleep, activity, and physiology, with precise synchronisation to environmental daily light cycles as its main function (entrainment). Studies in knockout mice showed that the clock genes perl, per2, c ryl, cry2 are essential to drive the mammalian circadian oscillation, but their precise role in entrainment remains unclear. Clock gene knockout mice are affected in their circadian light response. Previous work has shown that light induced behavioural pha se shifts and induction of the immediate early gene c-Fos in the central circadian pacemaker (suprachiasmatic nucleus; SCN) are affected by per and cry gene deletions. Such results are mostly interpreted as an effect caused by malfunction of the central pa cemaker. The hypothesis, however, that deletion of a clock genes is likely to affect the circadian organisation in the retina and may reduce its phototransduction efficiency has so far been overlooked. In this study, we want to separate the effect of per o r cry gene deletions on the light responses in the eye and the circadian system. Electro-retinogram, retinal c-Fos induction, SCN c-Fos induction, behavioural phase shifts will be quantified mperl''', per2~'~, perl'''!''', cryl''', cry2''', and wildtype mi ce. Differences in light responses will be correlated with the anatomy of classical and non-classical retinal photoreceptors. Aberations of rhythmicity in melatonin production and electrical activity in isolated retinas will be studied as a possible source for anatomical and light response differences. For these retinal preparations a new melatonin producing mouse model, bearing one of the clock gene deletions, will be developed. This project is not funded otherwise and although most equipment and material is available at the host institute, it can only be continued when additional scientific personnel can be hired. This re-integration grant provides the best financial possib

Convocatoria de propuestas

FP6-2002-MOBILITY-11
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Coordinador

RIJKSUNIVERSITEIT GRONINGEN.
Aportación de la UE
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Dirección
Broerstraat 5
GRONINGEN
Países Bajos

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Coste total
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