International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 4 - MAPPING AND CHARACTERISATION OF A NOVEL ENU MUTANT WITH A SHORT CIRCADIAN PERIOD AND REDUCED ENTRAINMENT TO LIGHT

Nolan P
MRC Mammalian Genetics Unit

Co-Authors: Bacon Y, Breeds S, Clay J, Ooi A, Kerr S
Institutions: MRC Mammalian Genetics Unit

We are conducting a screen in mice for ENU-induced mutations affecting circadian rhythms and entrainment to light. The screen consists of an assessment of mouse wheel-running activity in a 12:12 hr light:dark cycle for 7-10 days followed by assessment in constant darkness (DD) for 20 days. Responses to light are assessed using two protocols, a) a 15 minute light pulse given at circadian time 16 (CT16) on the tenth day in constant darkness and b) an additional 12 hrs of light upon transition from light:dark conditions to constant darkness. We have identified one particular dominant mutant line in our screen (PLAY 8) where both circadian and light-responsive parameters are affected. PLAY 8 mutants can exhibit a range of phenotypes including a shortening of the circadian period by one hour, free-running in light:dark conditions, arrhythmicity in constant darkness and reduced or absent responses to light using both protocols. A genome scan of backcross progeny detected one region of linkage on distal mouse Chr 8 and further fine mapping allowed us to narrow down the critical region to 10 Mb. No genes previously associated with circadian rhythms map to this region and no likely candidates have been identified using online genome browsers. We are continuing to refine the critical region using additional polymorphic markers and recombinants. In parallel, we are using qPCR in wild-type and mutant brain samples in an attempt to asses the effect of the mutation on the cyclical expression of core clock components such as clock, period and bmal1.


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