Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated -synuclein gene mutations precede central nervous system changes
Identifieur interne : 000466 ( Main/Exploration ); précédent : 000465; suivant : 000467Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated -synuclein gene mutations precede central nervous system changes
Auteurs : Yien-Ming Kuo ; Zhishan Li ; Yun Jiao ; Nathalie Gaborit ; Amar K. Pani ; Bonnie M. Orrison ; Benoit G. Bruneau ; Benoit I. Giasson ; Richard J. Smeyne ; Michael D. Gershon ; Robert L. Nussbaum [États-Unis]Source :
- Human Molecular Genetics [ 0964-6906 ] ; 2010-05-01.
Abstract
Parkinson disease (PD) is a neurodegenerative disease with motor as well as non-motor signs in the gastrointestinal tract that include dysphagia, gastroparesis, prolonged gastrointestinal transit time, constipation and difficulty with defecation. The gastrointestinal dysfunction commonly precedes the motor symptoms by decades. Most PD is sporadic and of unknown etiology, but a fraction is familial. Among familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes -synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates found in neurons in PD. We set out to develop transgenic mice expressing mutant -synuclein (either A53T or A30P) from insertions of an entire human SNCA gene as models for the familial disease. Both the A53T and A30P lines show robust abnormalities in enteric nervous system (ENS) function and synuclein-immunoreactive aggregates in ENS ganglia by 3 months of age. The A53T line also has abnormal motor behavior but neither demonstrates cardiac autonomic abnormalities, olfactory dysfunction, dopaminergic neurotransmitter deficits, Lewy body inclusions or neurodegeneration. These animals recapitulate the early gastrointestinal abnormalities seen in human PD. The animals also serve as an in vivo system in which to investigate therapies for reversing the neurological dysfunction that target -synuclein toxicity at its earliest stages.
Url:
DOI: 10.1093/hmg/ddq038
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated -synuclein gene mutations precede central nervous system changes</title><author><name sortKey="Kuo, Yien Ming" sort="Kuo, Yien Ming" uniqKey="Kuo Y" first="Yien-Ming" last="Kuo">Yien-Ming Kuo</name></author><author><name sortKey="Li, Zhishan" sort="Li, Zhishan" uniqKey="Li Z" first="Zhishan" last="Li">Zhishan Li</name></author><author><name sortKey="Jiao, Yun" sort="Jiao, Yun" uniqKey="Jiao Y" first="Yun" last="Jiao">Yun Jiao</name></author><author><name sortKey="Gaborit, Nathalie" sort="Gaborit, Nathalie" uniqKey="Gaborit N" first="Nathalie" last="Gaborit">Nathalie Gaborit</name></author><author><name sortKey="Pani, Amar K" sort="Pani, Amar K" uniqKey="Pani A" first="Amar K." last="Pani">Amar K. Pani</name></author><author><name sortKey="Orrison, Bonnie M" sort="Orrison, Bonnie M" uniqKey="Orrison B" first="Bonnie M." last="Orrison">Bonnie M. Orrison</name></author><author><name sortKey="Bruneau, Benoit G" sort="Bruneau, Benoit G" uniqKey="Bruneau B" first="Benoit G." last="Bruneau">Benoit G. Bruneau</name></author><author><name sortKey="Giasson, Benoit I" sort="Giasson, Benoit I" uniqKey="Giasson B" first="Benoit I." last="Giasson">Benoit I. Giasson</name></author><author><name sortKey="Smeyne, Richard J" sort="Smeyne, Richard J" uniqKey="Smeyne R" first="Richard J." last="Smeyne">Richard J. Smeyne</name></author><author><name sortKey="Gershon, Michael D" sort="Gershon, Michael D" uniqKey="Gershon M" first="Michael D." last="Gershon">Michael D. Gershon</name></author><author><name sortKey="Nussbaum, Robert L" sort="Nussbaum, Robert L" uniqKey="Nussbaum R" first="Robert L." last="Nussbaum">Robert L. Nussbaum</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:5227239BDF11AEFDE162723F5DD6194B8B48A631</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1093/hmg/ddq038</idno><idno type="url">https://api.istex.fr/document/5227239BDF11AEFDE162723F5DD6194B8B48A631/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001992</idno><idno type="wicri:Area/Main/Curation">001741</idno><idno type="wicri:Area/Main/Exploration">000466</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated -synuclein gene mutations precede central nervous system changes</title><author><name sortKey="Kuo, Yien Ming" sort="Kuo, Yien Ming" uniqKey="Kuo Y" first="Yien-Ming" last="Kuo">Yien-Ming Kuo</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Li, Zhishan" sort="Li, Zhishan" uniqKey="Li Z" first="Zhishan" last="Li">Zhishan Li</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Jiao, Yun" sort="Jiao, Yun" uniqKey="Jiao Y" first="Yun" last="Jiao">Yun Jiao</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Gaborit, Nathalie" sort="Gaborit, Nathalie" uniqKey="Gaborit N" first="Nathalie" last="Gaborit">Nathalie Gaborit</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Pani, Amar K" sort="Pani, Amar K" uniqKey="Pani A" first="Amar K." last="Pani">Amar K. Pani</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Orrison, Bonnie M" sort="Orrison, Bonnie M" uniqKey="Orrison B" first="Bonnie M." last="Orrison">Bonnie M. Orrison</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Bruneau, Benoit G" sort="Bruneau, Benoit G" uniqKey="Bruneau B" first="Benoit G." last="Bruneau">Benoit G. Bruneau</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Giasson, Benoit I" sort="Giasson, Benoit I" uniqKey="Giasson B" first="Benoit I." last="Giasson">Benoit I. Giasson</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Smeyne, Richard J" sort="Smeyne, Richard J" uniqKey="Smeyne R" first="Richard J." last="Smeyne">Richard J. Smeyne</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Gershon, Michael D" sort="Gershon, Michael D" uniqKey="Gershon M" first="Michael D." last="Gershon">Michael D. Gershon</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Nussbaum, Robert L" sort="Nussbaum, Robert L" uniqKey="Nussbaum R" first="Robert L." last="Nussbaum">Robert L. Nussbaum</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2010-05-01">2010-05-01</date><biblScope unit="volume">19</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1633">1633</biblScope><biblScope unit="page" to="1650">1650</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">5227239BDF11AEFDE162723F5DD6194B8B48A631</idno><idno type="DOI">10.1093/hmg/ddq038</idno><idno type="ArticleID">ddq038</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Parkinson disease (PD) is a neurodegenerative disease with motor as well as non-motor signs in the gastrointestinal tract that include dysphagia, gastroparesis, prolonged gastrointestinal transit time, constipation and difficulty with defecation. The gastrointestinal dysfunction commonly precedes the motor symptoms by decades. Most PD is sporadic and of unknown etiology, but a fraction is familial. Among familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes -synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates found in neurons in PD. We set out to develop transgenic mice expressing mutant -synuclein (either A53T or A30P) from insertions of an entire human SNCA gene as models for the familial disease. Both the A53T and A30P lines show robust abnormalities in enteric nervous system (ENS) function and synuclein-immunoreactive aggregates in ENS ganglia by 3 months of age. The A53T line also has abnormal motor behavior but neither demonstrates cardiac autonomic abnormalities, olfactory dysfunction, dopaminergic neurotransmitter deficits, Lewy body inclusions or neurodegeneration. These animals recapitulate the early gastrointestinal abnormalities seen in human PD. The animals also serve as an in vivo system in which to investigate therapies for reversing the neurological dysfunction that target -synuclein toxicity at its earliest stages.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Bruneau, Benoit G" sort="Bruneau, Benoit G" uniqKey="Bruneau B" first="Benoit G." last="Bruneau">Benoit G. Bruneau</name><name sortKey="Gaborit, Nathalie" sort="Gaborit, Nathalie" uniqKey="Gaborit N" first="Nathalie" last="Gaborit">Nathalie Gaborit</name><name sortKey="Gershon, Michael D" sort="Gershon, Michael D" uniqKey="Gershon M" first="Michael D." last="Gershon">Michael D. Gershon</name><name sortKey="Giasson, Benoit I" sort="Giasson, Benoit I" uniqKey="Giasson B" first="Benoit I." last="Giasson">Benoit I. Giasson</name><name sortKey="Jiao, Yun" sort="Jiao, Yun" uniqKey="Jiao Y" first="Yun" last="Jiao">Yun Jiao</name><name sortKey="Kuo, Yien Ming" sort="Kuo, Yien Ming" uniqKey="Kuo Y" first="Yien-Ming" last="Kuo">Yien-Ming Kuo</name><name sortKey="Li, Zhishan" sort="Li, Zhishan" uniqKey="Li Z" first="Zhishan" last="Li">Zhishan Li</name><name sortKey="Orrison, Bonnie M" sort="Orrison, Bonnie M" uniqKey="Orrison B" first="Bonnie M." last="Orrison">Bonnie M. Orrison</name><name sortKey="Pani, Amar K" sort="Pani, Amar K" uniqKey="Pani A" first="Amar K." last="Pani">Amar K. Pani</name><name sortKey="Smeyne, Richard J" sort="Smeyne, Richard J" uniqKey="Smeyne R" first="Richard J." last="Smeyne">Richard J. Smeyne</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Nussbaum, Robert L" sort="Nussbaum, Robert L" uniqKey="Nussbaum R" first="Robert L." last="Nussbaum">Robert L. Nussbaum</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000466 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000466 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:5227239BDF11AEFDE162723F5DD6194B8B48A631
|texte= Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated -synuclein gene mutations precede central nervous system changes
}}
| This area was generated with Dilib version V0.6.23. |  |