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The role of the Prader-Willi syndrome obesity protein, MAGEL2 in the proper functioning of circadian rhythm Open Access


Other title
Circadian rhythm
Prader-Willi syndrome
Type of item
Degree grantor
University of Alberta
Author or creator
Weselake, Sara Victoria
Supervisor and department
Wevrick, Rachel (Medical Genetics)
Examining committee member and department
McDermid, Heather (Medical Genetics, Biological Sciences)
Berry, Fred (Medical Genetics)
Godbout, Rosaline (Oncology)
Medical Sciences - Medical Genetics

Date accepted
Graduation date
Sara Victoria Weselake
Degree level
MAGEL2 is one of the five genes inactivated in Prader-Willi Syndrome (PWS), a genetic disorder, manifesting with symptoms of developmental delay and morbid obesity. Magel2 is highly expressed in the suprachiasmatic nucleus, which is the location of the central clock or circadian pacemaker. Magel2 knockout mice exhibit defects in circadian rhythm. I hypothesized that Magel2 plays a role in one of the inter-connecting feedback loops that control circadian rhythm in suprachiasmatic neurons. I determined that Magel2 acts as a repressive protein in the cycle’s feedback loop using a luciferase assay. Magel2 exerts this effect by restricting the movement of Bmal1 into the nucleus. Magel2 levels are then reduced by increasing Per2, associated with increase movement into the nucleus, as determined by experiments examining subcellular localization and effects on protein levels. Loss of Magel2 in PWS may contribute to sleep abnormalities in this disorder, specifically the cycling between different sleep stages.
License granted by Sara Weselake ( on 2010-10-01T03:50:00Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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File title: Magel2 and Circadian Rhythm
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