Rodent Models of Autosomal Recessive Parkinson Disease

Suzana Gispert, Georg Auburger, Korah Pushpamangalam Kuruvilla, Mark Ledoux

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Using traditional linkage analysis and positional cloning, mutations in genes encoding PARKIN, PINK1, and DJ-1 have been causally associated with the autosomal recessive Parkinson disease (PD) variants PARK2, PARK6, and PARK7, respectively. Traditional germline knock-out models targeting PARKIN, PINK1, and DJ-1 have failed to recapitulate the preferential affection of the substantia nigra pars compacta by core features of late-stage PD, particularly the formation of classical Lewy body and Lewy neurite protein aggregates and the selective loss of dopaminergic neurons, which result in the classical phenotype of deficient spontaneous locomotion in PD. However, in vivo and in vitro studies using knock-out, knock-down, and overexpression have shown a role for these proteins in stress-response and quality-control, particularly in the autophagic degradation of dysfunctional mitochondria as a crucial pathobiological feature of Parkinsonism. Although face validity has been limited to date, rodent PD models are improving, by combining stressors with the absence of stress-response, by using conditional knock-outs, and by overexpressing dominant-negative factors. Rodent models will be crucial to understand the cell-type specific neurodegeneration in PD and to identify disease preventative treatments that target central pathogenic processes rather than providing only symptomatic benefit. In this chapter, we review rodent models for three recessive forms of PD and a variety of multiplex mutants that have yielded important insights into the altered biology of mitochondria in PD.

Original languageEnglish (US)
Title of host publicationMovement Disorders
Subtitle of host publicationGenetics and Models: Second Edition
PublisherElsevier Inc.
Pages329-343
Number of pages15
ISBN (Print)9780124051959
DOIs
StatePublished - Jan 1 2015

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Parkinson Disease
Rodentia
Mitochondria
Rodent Diseases
Lewy Bodies
Dopaminergic Neurons
Parkinsonian Disorders
Neurites
Locomotion
Heat-Shock Proteins
Reproducibility of Results
Quality Control
Organism Cloning
Phenotype
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Gispert, S., Auburger, G., Pushpamangalam Kuruvilla, K., & Ledoux, M. (2015). Rodent Models of Autosomal Recessive Parkinson Disease. In Movement Disorders: Genetics and Models: Second Edition (pp. 329-343). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-405195-9.00019-6

Rodent Models of Autosomal Recessive Parkinson Disease. / Gispert, Suzana; Auburger, Georg; Pushpamangalam Kuruvilla, Korah; Ledoux, Mark.

Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc., 2015. p. 329-343.

Research output: Chapter in Book/Report/Conference proceedingChapter

Gispert, S, Auburger, G, Pushpamangalam Kuruvilla, K & Ledoux, M 2015, Rodent Models of Autosomal Recessive Parkinson Disease. in Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc., pp. 329-343. https://doi.org/10.1016/B978-0-12-405195-9.00019-6
Gispert S, Auburger G, Pushpamangalam Kuruvilla K, Ledoux M. Rodent Models of Autosomal Recessive Parkinson Disease. In Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc. 2015. p. 329-343 https://doi.org/10.1016/B978-0-12-405195-9.00019-6
Gispert, Suzana ; Auburger, Georg ; Pushpamangalam Kuruvilla, Korah ; Ledoux, Mark. / Rodent Models of Autosomal Recessive Parkinson Disease. Movement Disorders: Genetics and Models: Second Edition. Elsevier Inc., 2015. pp. 329-343
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