Linked Life Data

10893242

Source:http://linkedlifedata.com/resource/pubmed/id/10893242

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2000-11-20
pubmed:abstractText
Nonphysiological truncations of apolipoprotein (apo) B-100 cause familial hypobetalipoproteinemia (FHBL) in humans and mice. An elucidation of the mechanisms underlying the FHBL phenotypes may provide valuable information on the metabolism of apo B-containing lipoproteins and the structure-function relationship of apo B. To generate a faithful mouse model of human FHBL, a subtle mutation was introduced into the mouse apo B gene by targeting embryonic stem cells using homologous recombination followed by removal of the selection marker gene by Cre-loxP-mediated site-specific recombination. The engineered mice bear a premature stop codon at residue 1767 and a 42-base pair loxP inserted into intron 24 of the apo B gene, thus closely resembling the apo B-38.9-producing mutation in humans. Apo B-38.9 was the sole apo B protein in homozygote (apob(38.9/38.9)) plasma. In heterozygotes (apob(+/)(38. 9)), apo B-100 and apo B-48 were reduced by 75 and 40%, respectively, and apo B-38.9 represented 20% of total circulating apo B. Hepatic apo B-38.9 mRNA levels were reduced by 40%. In cultured apob(+/)(38. 9) hepatocytes, apo B-100 was produced in trace quantities, and the synthesis rate of apo B-38.9 relative to apo B-48 was reduced by 40%. However, almost equimolar amounts of apo B-38.9 and apo B-48 were secreted into the media. Pulse-chase studies revealed that apo B-38. 9 was secreted at a faster rate and more efficiently than apoB-48. Nevertheless, both apob(+/)(38.9) and apob(38.9/38.9) mice had reduced hepatic triglyceride secretion rates and fatty livers. Thus, low mRNA levels or defective secretion of apo B-38.9 may not be responsible for the FHBL phenotypes caused by the apo B-38.9 mutation. Rather, a reduced capacity of apo B-38.9 for triglyceride transport may account for the fatty livers in these mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32807-15
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10893242-Animals, pubmed-meshheading:10893242-Apolipoproteins B, pubmed-meshheading:10893242-Base Sequence, pubmed-meshheading:10893242-Cells, Cultured, pubmed-meshheading:10893242-Cholesterol, pubmed-meshheading:10893242-Fatty Liver, pubmed-meshheading:10893242-Hepatocytes, pubmed-meshheading:10893242-Humans, pubmed-meshheading:10893242-Hypobetalipoproteinemias, pubmed-meshheading:10893242-Intestine, Small, pubmed-meshheading:10893242-Liver, pubmed-meshheading:10893242-Mice, pubmed-meshheading:10893242-Mice, Inbred C57BL, pubmed-meshheading:10893242-Mice, Inbred Strains, pubmed-meshheading:10893242-Mice, Transgenic, pubmed-meshheading:10893242-Phospholipids, pubmed-meshheading:10893242-Polyethylene Glycols, pubmed-meshheading:10893242-Polymerase Chain Reaction, pubmed-meshheading:10893242-Sequence Alignment, pubmed-meshheading:10893242-Sequence Homology, Nucleic Acid, pubmed-meshheading:10893242-Surface-Active Agents, pubmed-meshheading:10893242-Triglycerides
pubmed:year
2000
pubmed:articleTitle
A targeted apolipoprotein B-38.9-producing mutation causes fatty livers in mice due to the reduced ability of apolipoprotein B-38.9 to transport triglycerides.
pubmed:affiliation
Division of Atherosclerosis, Nutrition and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. zchen@im.wustl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't