Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a]
In this study, we created LDL receptor (LDLr) defective (WHHL) transgenic rabbits expressing human apo[a] to examine whether LDLr mediates the Lp[a] clearance from the plasma. By crossbreeding WHHL rabbits with human apo[a] transgenic rabbits, we obtained two groups of human apo[a] transgenic rabbit...
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| Format: | Article |
| Language: | English |
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Elsevier
2000-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520320435 |
| _version_ | 1818739313999872000 |
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| author | Jianglin Fan Mireille Challah Hiroaki Shimoyamada Masashi Shiomi Santica Marcovina Teruo Watanabe |
| author_facet | Jianglin Fan Mireille Challah Hiroaki Shimoyamada Masashi Shiomi Santica Marcovina Teruo Watanabe |
| author_sort | Jianglin Fan |
| collection | DOAJ |
| description | In this study, we created LDL receptor (LDLr) defective (WHHL) transgenic rabbits expressing human apo[a] to examine whether LDLr mediates the Lp[a] clearance from the plasma. By crossbreeding WHHL rabbits with human apo[a] transgenic rabbits, we obtained two groups of human apo[a] transgenic rabbits with defective LDLr functions: apo[a]+/0 WHHL heterozygous (LDLr+/−) and apo[a]+/0 WHHL homozygous (LDLr−/−) rabbits. The lipid and lipoprotein levels of human apo[a] WHHL rabbits were compared to those of human apo[a] transgenic rabbits with normal LDLr functions (LDLr+/+). The apo[a] production rate was evaluated by analyzing apo[a] mRNA expression in the liver, the major site for apo[a] synthesis in transgenic rabbits. We found that pre-β lipoproteins were markedly increased accompanied by a 2-fold increase in the plasma Lp[a] in apo[a]+/0/LDLr+/− rabbits and a 4.2-fold increase in apo[a]+/0/LDLr−/− rabbits compared with that in apo[a]+/0 rabbits with normal LDLr function. In apo[a]+/0/LDLr−/− rabbits, there was a marked increase in plasma total cholesterol and triglycerides, as was found in their counterpart non-transgenic WHHL rabbits. Northern blot analysis revealed that hepatic apo[a] expression in WHHL transgenic rabbits was similar to that in LDLr+/+ transgenic rabbits, suggesting the accumulation of plasma Lp[a] in WHHL transgenic rabbits was not due to increased apo[a] synthesis.In conclusion, absence of a functional LDLr leads to a marked accumulation of plasma Lp[a] in human apo[a] transgenic WHHL rabbits and LDLr may participate in the catabolism of Lp[a] in rabbits. |
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| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
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| publishDate | 2000-06-01 |
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| series | Journal of Lipid Research |
| spelling | doaj.art-97c182e71d264db2a56c8825478d88e72022-12-21T21:25:47ZengElsevierJournal of Lipid Research0022-22752000-06-0141610041012Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a]Jianglin Fan0Mireille Challah1Hiroaki Shimoyamada2Masashi Shiomi3Santica Marcovina4Teruo Watanabe5To whom correspondence should be addressed.; Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, 305-8575 JapanDepartment of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, 305-8575 JapanDepartment of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, 305-8575 JapanInstitute for Experimental Animals, Kobe University School of Medicine, Kobe, JapanNorthwest Lipid Research Laboratories, University of Washington, Seattle, WA 98103Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, 305-8575 JapanIn this study, we created LDL receptor (LDLr) defective (WHHL) transgenic rabbits expressing human apo[a] to examine whether LDLr mediates the Lp[a] clearance from the plasma. By crossbreeding WHHL rabbits with human apo[a] transgenic rabbits, we obtained two groups of human apo[a] transgenic rabbits with defective LDLr functions: apo[a]+/0 WHHL heterozygous (LDLr+/−) and apo[a]+/0 WHHL homozygous (LDLr−/−) rabbits. The lipid and lipoprotein levels of human apo[a] WHHL rabbits were compared to those of human apo[a] transgenic rabbits with normal LDLr functions (LDLr+/+). The apo[a] production rate was evaluated by analyzing apo[a] mRNA expression in the liver, the major site for apo[a] synthesis in transgenic rabbits. We found that pre-β lipoproteins were markedly increased accompanied by a 2-fold increase in the plasma Lp[a] in apo[a]+/0/LDLr+/− rabbits and a 4.2-fold increase in apo[a]+/0/LDLr−/− rabbits compared with that in apo[a]+/0 rabbits with normal LDLr function. In apo[a]+/0/LDLr−/− rabbits, there was a marked increase in plasma total cholesterol and triglycerides, as was found in their counterpart non-transgenic WHHL rabbits. Northern blot analysis revealed that hepatic apo[a] expression in WHHL transgenic rabbits was similar to that in LDLr+/+ transgenic rabbits, suggesting the accumulation of plasma Lp[a] in WHHL transgenic rabbits was not due to increased apo[a] synthesis.In conclusion, absence of a functional LDLr leads to a marked accumulation of plasma Lp[a] in human apo[a] transgenic WHHL rabbits and LDLr may participate in the catabolism of Lp[a] in rabbits.http://www.sciencedirect.com/science/article/pii/S0022227520320435lipoprotein[a]WHHL rabbitapolipoprotein[a]LDL receptortransgenic rabbitmetabolism |
| spellingShingle | Jianglin Fan Mireille Challah Hiroaki Shimoyamada Masashi Shiomi Santica Marcovina Teruo Watanabe Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a] Journal of Lipid Research lipoprotein[a] WHHL rabbit apolipoprotein[a] LDL receptor transgenic rabbit metabolism |
| title | Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a] |
| title_full | Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a] |
| title_fullStr | Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a] |
| title_full_unstemmed | Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a] |
| title_short | Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a] |
| title_sort | defects of the ldl receptor in whhl transgenic rabbits lead to a marked accumulation of plasma lipoprotein a |
| topic | lipoprotein[a] WHHL rabbit apolipoprotein[a] LDL receptor transgenic rabbit metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520320435 |
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