Date of Award

Spring 2011

Document Type

Restricted Thesis

Terms of Use

© 2011 Youda Cao. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.

Degree Name

Bachelor of Arts

Department

Biology Department

First Advisor

Colin Purrington

Second Advisor

Kathleen King Siwicki

Abstract

The hereditary spastic paraplegias (HSPs) are a group of inherited neurological disorders that are characterized by spastic lower extremity weakness due to a retrograde degradation of corticospinal motor neurons. SPG3A, the gene locus coding for atlastin-l, is the most common cause of early onset HSP. Atlastin-l is a dynamin-like GTPase with a role in formation of the ER network. Implementing knock-down of atlastin-l expression in neurons using interfering RNA reduces the number of neuronal processes and impairs axon formation and elongation during development. Several point mutations found in patients, such as K80A, impair GTPase activity of atlastin-1. In this experiment, I sought to determine if the GTPase activity of atlastin-l is specifically necessary for normal axon growth, in contrast to the whole protein interaction. A knock-in model of the point mutation was created and propogated. It was found that in cultured cortical knock-in neurons when atlastin-l GTPase was limited, the axon lengths ofthe cells were significantly shorter when compared with those in wild-type neurons early in neuronal development. Therefore, the lack of normal axon growth in SPG3A may contribute to its basis of early onset, and may result from a limited GTPase function.

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