Source:http://linkedlifedata.com/resource/pubmed/id/14659996
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2003-12-8
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pubmed:abstractText |
The Smith-Lemli-Opitz syndrome (SLOS) is a malformation/mental retardation syndrome resulting from an inborn error in 3beta-hydroxysteroid Delta7-reductase (DHCR7), the terminal enzyme required for cholesterol biosynthesis. Using a targeting strategy designed to virtually eliminate Dhcr7 activity, we have created a SLOS mouse model that exhibits commissural deficiencies, hippocampal abnormalities, and hypermorphic development of serotonin (5-HT) neurons. The latter is of particular interest with respect to current evidence that serotonin plays a significant role in autism spectrum disorders and the recent clinical observation that 50% of SLOS patients present with autistic behavior. Immunohistochemical analyses have revealed a 306% increase in the area of 5-HT immunoreactivity (5-HT IR) in the hindbrains of mutant (Dhcr7-/-) mice as compared to age-matched wild type animals. Amount of 5-HT IR was measured as total area of IR per histological section. Additionally, a regional increase as high as 15-fold was observed for the most lateral sagittal hindbrain sections. In Dhcr7-/- mice, an expansion of 5-HT IR into the ventricular zone and floor plate region was observed. In addition, the rostral and caudal raphe groups exhibited a radial expansion in Dhcr7-/- mice, with 5-HT IR cells present in locations not seen in wild type mice. This increase in 5-HT IR appears to represent an increase in total number of 5-HT neurons and fibers. These observations may help explain the behavioral phenotype seen in SLOS, and provide clues for future therapeutic interventions that utilize pharmacological modulation of the serotonergic system.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7-dehydrocholesterol reductase,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases Acting on CH-CH...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0736-5748
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
451-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:14659996-Animals,
pubmed-meshheading:14659996-Autistic Disorder,
pubmed-meshheading:14659996-Cell Count,
pubmed-meshheading:14659996-Disease Models, Animal,
pubmed-meshheading:14659996-Embryo, Mammalian,
pubmed-meshheading:14659996-Female,
pubmed-meshheading:14659996-Genotype,
pubmed-meshheading:14659996-Immunohistochemistry,
pubmed-meshheading:14659996-Male,
pubmed-meshheading:14659996-Mice,
pubmed-meshheading:14659996-Mice, Inbred C57BL,
pubmed-meshheading:14659996-Mice, Knockout,
pubmed-meshheading:14659996-Neurons,
pubmed-meshheading:14659996-Oxidoreductases Acting on CH-CH Group Donors,
pubmed-meshheading:14659996-Raphe Nuclei,
pubmed-meshheading:14659996-Receptors, Serotonin,
pubmed-meshheading:14659996-Rhombencephalon,
pubmed-meshheading:14659996-Serotonin,
pubmed-meshheading:14659996-Smith-Lemli-Opitz Syndrome
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pubmed:year |
2003
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pubmed:articleTitle |
Abnormal serotonergic development in a mouse model for the Smith-Lemli-Opitz syndrome: implications for autism.
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pubmed:affiliation |
Department of Cell and Developmental Biology, The University of North Carolina, Chapel Hill, NC 27599-7178, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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