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rdf:type |
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lifeskim:mentions |
umls-concept:C0011847,
umls-concept:C0021492,
umls-concept:C0025914,
umls-concept:C0025933,
umls-concept:C0026809,
umls-concept:C0028754,
umls-concept:C0205171,
umls-concept:C0299583,
umls-concept:C0443252,
umls-concept:C0679058,
umls-concept:C1547699,
umls-concept:C1564874,
umls-concept:C1947976,
umls-concept:C2700640
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pubmed:issue |
25
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pubmed:dateCreated |
1998-1-15
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pubmed:abstractText |
The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes mellitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2-5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-2547998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-2554300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-6358778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7046470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7504271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7515101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7584109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7584987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7624776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7624778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7663508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7791793,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7842013,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-7984236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8449404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8548812,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8618912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8892935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8898192,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8900534,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8934224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8939859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8957370,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8962136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-8962149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-9000710,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-9037069,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-9055858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9391128-9114043
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
94
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13921-6
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:9391128-Animals,
pubmed-meshheading:9391128-Base Sequence,
pubmed-meshheading:9391128-Blood Glucose,
pubmed-meshheading:9391128-DNA Primers,
pubmed-meshheading:9391128-Dependovirus,
pubmed-meshheading:9391128-Diabetes Mellitus, Type 2,
pubmed-meshheading:9391128-Eating,
pubmed-meshheading:9391128-Female,
pubmed-meshheading:9391128-Gene Therapy,
pubmed-meshheading:9391128-Genetic Vectors,
pubmed-meshheading:9391128-Glucose Tolerance Test,
pubmed-meshheading:9391128-Injections, Intramuscular,
pubmed-meshheading:9391128-Insulin,
pubmed-meshheading:9391128-Leptin,
pubmed-meshheading:9391128-Mice,
pubmed-meshheading:9391128-Mice, Inbred C57BL,
pubmed-meshheading:9391128-Mice, Obese,
pubmed-meshheading:9391128-Obesity,
pubmed-meshheading:9391128-Proteins,
pubmed-meshheading:9391128-Recombination, Genetic,
pubmed-meshheading:9391128-Weight Gain
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pubmed:year |
1997
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pubmed:articleTitle |
Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin.
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pubmed:affiliation |
Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.
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pubmed:publicationType |
Journal Article
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