ParkinsonCanadaV1, Main, Exploration, bibRecord, 001145

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

Identifieur interne : 001145 ( Main/Exploration ); précédent : 001144; suivant : 001146

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

Auteurs : Maxime W. C. Rousseaux ; Paul C. Marcogliese ; Dianbo Qu ; Sarah J. Hewitt ; Sarah Seang ; Raymond H. Kim ; Ruth S. Slack ; Michael G. Schlossmacher ; Diane C. Lagace ; Tak W. Mak ; David S. Park [Corée du Sud]

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2012.

RBID : PMC:3465410

English descriptors

KwdEn :
- Animals, Disease Models, Animal, Dopaminergic Neurons (metabolism), Dopaminergic Neurons (pathology), Humans, Intracellular Signaling Peptides and Proteins, Locus Coeruleus (metabolism), Locus Coeruleus (pathology), Mice, Mice, Knockout, Nerve Tissue Proteins, Oncogene Proteins, Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (pathology), Substantia Nigra (metabolism), Substantia Nigra (pathology).
MESH :
- chemical : Intracellular Signaling Peptides and Proteins, Nerve Tissue Proteins, Oncogene Proteins.
- genetics : Parkinson Disease.
- metabolism : Dopaminergic Neurons, Locus Coeruleus, Parkinson Disease, Substantia Nigra.
- pathology : Dopaminergic Neurons, Locus Coeruleus, Parkinson Disease, Substantia Nigra.
- Animals, Disease Models, Animal, Humans, Mice, Mice, Knockout.

Abstract

DJ-1 mutations cause autosomal recessive early-onset Parkinson disease (PD). We report a model of PD pathology: the DJ1-C57 mouse. A subset of DJ-1–nullizygous mice, when fully backcrossed to a C57BL/6J background, display dramatic early-onset unilateral loss of dopaminergic (DA) neurons in their substantia nigra pars compacta, progressing to bilateral degeneration of the nigrostriatal axis with aging. In addition, these mice exhibit age-dependent bilateral degeneration at the locus ceruleus nucleus and display mild motor behavior deficits at aged time points. These findings effectively recapitulate the early stages of PD. Therefore, the DJ1-C57 mouse provides a tool to study the preclinical aspects of neurodegeneration. Importantly, by exome sequencing, we identify candidate modifying genes that segregate with the phenotype, providing potentially critical clues into how certain genes may influence the penetrance of DJ-1–related degeneration in mice.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465410

DOI: 10.1073/pnas.1205102109
PubMed: 23019375
PubMed Central: 3465410

Affiliations:

Corée du Sud

Le document en format XML

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, K1H 8M5;</nlm:aff>
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, K1H 8M5;</nlm:aff>
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, Geumjeong-gu, Busan 609-735,<country>South Korea</country>
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<front><div type="abstract" xml:lang="en"><p>DJ-1 mutations cause autosomal recessive early-onset Parkinson disease (PD). We report a model of PD pathology: the DJ1-C57 mouse. A subset of DJ-1–nullizygous mice, when fully backcrossed to a C57BL/6J background, display dramatic early-onset unilateral loss of dopaminergic (DA) neurons in their <italic>substantia nigra pars compacta</italic>
, progressing to bilateral degeneration of the nigrostriatal axis with aging. In addition, these mice exhibit age-dependent bilateral degeneration at the <italic>locus ceruleus</italic>
 nucleus and display mild motor behavior deficits at aged time points. These findings effectively recapitulate the early stages of PD. Therefore, the DJ1-C57 mouse provides a tool to study the preclinical aspects of neurodegeneration. Importantly, by exome sequencing, we identify candidate modifying genes that segregate with the phenotype, providing potentially critical clues into how certain genes may influence the penetrance of DJ-1–related degeneration in mice.</p>
</div>
</front>
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<affiliations><list><country><li>Corée du Sud</li>
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<tree><noCountry><name sortKey="Hewitt, Sarah J" sort="Hewitt, Sarah J" uniqKey="Hewitt S" first="Sarah J." last="Hewitt">Sarah J. Hewitt</name>
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<name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name>
<name sortKey="Marcogliese, Paul C" sort="Marcogliese, Paul C" uniqKey="Marcogliese P" first="Paul C." last="Marcogliese">Paul C. Marcogliese</name>
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<name sortKey="Seang, Sarah" sort="Seang, Sarah" uniqKey="Seang S" first="Sarah" last="Seang">Sarah Seang</name>
<name sortKey="Slack, Ruth S" sort="Slack, Ruth S" uniqKey="Slack R" first="Ruth S." last="Slack">Ruth S. Slack</name>
</noCountry>
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La maladie de Parkinson au Canada (serveur d'exploration)

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

Source :

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.