| Four strains of spontaneously hyperlipidemic (SHL) mice: phenotypic distinctions determined by genetic backgrounds. | |
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MedLine Citation:
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PMID: 11866033 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Spontaneously hyperlipidemic (SHL) mice are Japanese wild mice (KOR) with disruption of the apolipoprotein E (Apo E) gene. These mice (KOR-Apoe(shl)) are superhypercholesterolemic and develop severe xanthoma, but their atherosclerosis is relatively mild compared with Apo E knockout mice. First, we tested whether this distinction is due to additional mutation of the Apoc1 and/or Apoc2 genes in KOR-Apoe(shl). Southern blot analysis, but found no gross disruption of these genes. Next, we tested whether the phenotypic distinction is due to differences in the genetic background. To this end, we established three lines of congenic SHL mice with a genetic background of C57BL/6, BALB/c or C3H/He, and named them, respectively, C57BL/6.KOR-Apoe(shl) (B6.KOR-Apoe(shl)), BALB/c.KOR-Apoe(shl) (C.KOR-Apoe(shl)) and C3H/He.KOR-Apoe(shl) (C3.KOR-Apoe(shl)). Hypercholesterolemia was most severe in KOR-Apoe(shl) followed the by others as follows; KOR-Apoe(shl)>>C3.KOR-Apoe(shl)>C.KOR-Apoe(shl)>B6.KOR-Apoe(shl). In contrast, atherosclerosis was most severe in B6.KOR Apoe(shl) followed by the others: B6.KOR-Apoe(shl)>C.KOR-Apoe(shl)>>C3.KOR-Apoe(shl)> or =KOR-Apoe(shl). This order, however, did not match that in xanthoma, which was highly prominent in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KORApoe(shl). This order, however, did not match that in xanthoma, which was highly prominant in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KOR-Apoe(shl). These distinctions suggest that the severity of each of the phenotypes is determined by distinct genetic backgrounds which probably are composed of polymorphism of lipid metabolism-related proteins. We found that apolipoprotein A-I is decreased in each SHL strain and polymorphic between B6.KOR-Apoe(shl) and the other strains examined. This polymorphism may be related to the most severe atherosclerosis observed in B6.KOR-Apoe(shl). It is most likely that combination of such polymorphisms is due to the genetic background accountable for phenotype distinctions. |
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Authors:
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Y Matsushima; T Sakurai; A Ohoka; T Ohnuki; N Tada; Y Asoh; M Tachibana |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of atherosclerosis and thrombosis Volume: 8 ISSN: 1340-3478 ISO Abbreviation: J. Atheroscler. Thromb. Publication Date: 2001 |
Date Detail:
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Created Date: 2002-02-27 Completed Date: 2002-08-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9506298 Medline TA: J Atheroscler Thromb Country: Japan |
Other Details:
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Languages: eng Pagination: 71-9 Citation Subset: IM |
Affiliation:
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Research Institute, Saitama Cancer Center, Ina, Japan. matsu@cancer-c.pref.saitama.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arteriosclerosis / genetics, pathology Blotting, Southern Blotting, Western Cholesterol / blood Hyperlipidemias / genetics* Lipoproteins / classification Mice Mice, Mutant Strains / genetics* Phenotype Species Specificity Xanthomatosis / genetics, pathology |
| Chemical | |
Reg. No./Substance:
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0/Lipoproteins; 57-88-5/Cholesterol |
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