Neurodegeneration and Failure of Autophagy in an Atp13a2 Knockout Mouse of Juvenile Parkinsonism
AdvisorKruer, Michael C.
Hammer, Ronald P.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractParkinson Disease (PD) is a neurodegenerative disorder characterized by motor and cognitive decline. While the majority of PD cases are sporadic cases in older individuals, 5-10% of cases are familial and juvenile forms of parkinsonism. Several genes have been associated with familial parkinsonism, including the gene ATP13A2, found mutated in cases of juvenile parkinsonism. ATP13A2 is a P-type ATPase protein, and its function has been implicated in the transport of polyamines, with loss of ATP13A2 resulting in cell toxicity due to the accumulation of polyamines in endolysosomes. Mutations in ATP13A2 have also been associated with the lysosomal storage disorder Neuronal Ceroid Lipofuscinosis, and additional studies have also suggested a role of ATP13A2 in lysosomal function and autophagy. Two prior published mouse models with mutations in Atp13a2 have exhibited a mild PD phenotype, and this thesis aims to characterize a novel Atp13a2 mouse model with a deletion of exons 21-29, to determine if this novel model better recapitulates the PD phenotype compared to existing Atp13a2 mouse models.
Degree ProgramGraduate College
Clinical Translational Sciences