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Cited by 477Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeurological disorders and treatments

Parkin-deficient mice are not a robust model of parkinsonism

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Perez, Francisco A., Palmiter, Richard D.·2005·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0409598102PMC PMC548311
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Abstract

Mutations in the human parkin gene cause autosomal recessive juvenile parkinsonism, a heritable form of Parkinson's disease (PD). To determine whether mutations in the mouse parkin gene ( Park2 ) also result in a parkinsonian phenotype, we generated mice with a targeted deletion of parkin exon 2. Using an extensive behavioral screen, we evaluated neurological function, motor ability, emotionality, learning, and memory in aged Parkin-deficient mice. The behavioral profile of Parkin-deficient mice on a B6;129S4 genetic background was strikingly similar to that of control mice, and most differences were not reproducible by using coisogenic mice on a 129S4 genetic background. Moreover, catecholamine levels in the striatum, olfactory bulb, and spinal cord of Parkin-deficient mice were normal. In contrast to previous studies using independently generated Parkin-deficient mice, we found no evidence for nigrostriatal, cognitive, or noradrenergic dysfunction. Understanding why Parkin-deficient mice do not exhibit robust signs of parkinsonism could advance knowledge and treatment of PD.

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  • Parkin-deficient mice and mice expressing a dominant negative form of Nrdp1 are not reported to have significant neurodegenerative disease.

    “Importantly, parkin-deficient mice and mice expressing a dominant negative form of Nrdp1 are not reported to have significant neurodegenerative disease171819.”

    From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [17]

    The Discussion reports intact substantia nigra dopamine neurons and no pathology in aged Parkin-deficient mice, supporting the parkin portion of the claim. Our copy does not report findings for mice expressing dominant-negative Nrdp1, so it does not support that portion. (LLM, conf=0.87)

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  • Lack of reported neurodegeneration in parkin-deficient and Nrdp1 mutant mice makes it unlikely that the Nrdp1 interaction explains the finding of neurodegeneration in Clec16a mutant mice.

    “The lack of reported neurodegeneration in parkin-deficient and Nrdp1 mutant mice171819 makes it unlikely that this interaction explains our finding of neurodegeneration in Clec16a mutant mice.”

    From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [17]

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Authors
Perez, F. A., & Palmiter, R. D.
Affiliations
Howard Hughes Medical Institute (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2005-01-31
Volume
102
Issue
6
Pages
2174-2179
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0409598102
PMC
PMC548311
OpenAlex
W2129698492
Cited by
477
References
45
Citations by year
2026: 6 · 2025: 9 · 2024: 18 · 2023: 18 · 2022: 31 · 2021: 33 · 2020: 29 · 2019: 18 · 2018: 24 · 2017: 18 · 2016: 19 · 2015: 17 · 2014: 26 · 2013: 21 · 2012: 27
FWCI
19.69
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
Parkin, PARK2, juvenile parkinsonism, autosomal recessive juvenile parkinsonism, Parkinson's disease, exon 2 deletion, behavioral phenotypes, motor function, emotionality, learning and memory, catecholamine levels, noradrenergic dysfunction, genetic background effects, B6
MeSH terms
Amphetamines, Animals, Behavior, Animal, Disease Models, Animal, Emotions, Genotype, Humans, Learning, Memory, Mice, Inbred C57BL, Motor Activity, Nerve Tissue, Parkinson Disease, Phenotype, Mice, Knockout, Ubiquitin-Protein Ligases, Mice

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