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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
51
|
| pubmed:dateCreated |
1999-1-26
|
| pubmed:abstractText |
Familial hypobetalipoproteinemia, a syndrome characterized by abnormally low plasma levels of low density lipoprotein cholesterol, is caused by mutations in the apolipoprotein (apo) B gene that interfere with the synthesis of a full-length apoB100. In many cases of familial hypobetalipoproteinemia, nonsense or frameshift mutations result in the synthesis of a truncated apoB protein. To understand why these mutations result in low plasma cholesterol levels, we used gene targeting in mouse embryonic stem cells to introduce a nonsense mutation (N1785Stop) into exon 26 of the mouse Apob gene. The sole product of this mutant Apob allele was a truncated apoB, apoB39. Mice homozygous for this "apoB39-only" (Apob39) allele had low plasma levels of apoB39 and markedly reduced plasma levels of very low density lipoprotein and low density lipoprotein cholesterol when fed a high fat diet. Analysis of liver and intestinal RNA from heterozygous apoB39-only mice revealed that the Apob39 mRNA levels were 60-70% lower than those from the wild-type allele. Interestingly, apoB39 was not cleared as rapidly from the plasma as apoB48. The apoB39-only mice provide new insights into the mechanisms of familial hypobetalipoproteinemia and the structural features of apoB that are important for lipoprotein metabolism.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins B,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Codon, Nonsense,
http://linkedlifedata.com/resource/pubmed/chemical/Codon, Terminator,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
18
|
| pubmed:volume |
273
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
33977-84
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9852051-Animals,
pubmed-meshheading:9852051-Apolipoproteins B,
pubmed-meshheading:9852051-Base Sequence,
pubmed-meshheading:9852051-Chimera,
pubmed-meshheading:9852051-Cholesterol,
pubmed-meshheading:9852051-Codon, Nonsense,
pubmed-meshheading:9852051-Codon, Terminator,
pubmed-meshheading:9852051-Dietary Fats,
pubmed-meshheading:9852051-Exons,
pubmed-meshheading:9852051-Female,
pubmed-meshheading:9852051-Frameshift Mutation,
pubmed-meshheading:9852051-Hypobetalipoproteinemias,
pubmed-meshheading:9852051-Lipoproteins,
pubmed-meshheading:9852051-Male,
pubmed-meshheading:9852051-Mice,
pubmed-meshheading:9852051-Mice, Inbred C57BL,
pubmed-meshheading:9852051-Mice, Mutant Strains,
pubmed-meshheading:9852051-Mutagenesis, Site-Directed,
pubmed-meshheading:9852051-Oligodeoxyribonucleotides,
pubmed-meshheading:9852051-Stem Cells
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
A gene-targeted mouse model for familial hypobetalipoproteinemia. Low levels of apolipoprotein B mRNA in association with a nonsense mutation in exon 26 of the apolipoprotein B gene.
|
| pubmed:affiliation |
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94141-9100, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|