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Defects of the LDL receptor in WHHL transgenic rabbits lead to a marked accumulation of plasma lipoprotein[a]
- Source :
- Journal of Lipid Research, Vol 41, Iss 6, Pp 1004-1012 (2000), Scopus-Elsevier
- Publication Year :
- 2000
- Publisher :
- Elsevier, 2000.
-
Abstract
- 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](1/0) 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-beta 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.
- Subjects :
- Plasma lipoprotein
medicine.medical_specialty
Transgene
QD415-436
Biochemistry
Animals, Genetically Modified
Endocrinology
apolipoprotein[a]
Internal medicine
medicine
Animals
Humans
WHHL rabbit
Northern blot
RNA, Messenger
cardiovascular diseases
biology
Catabolism
Chemistry
food and beverages
nutritional and metabolic diseases
LDL receptor
Cell Biology
Metabolism
Lipoprotein(a)
transgenic rabbit
Receptors, LDL
biology.protein
lipids (amino acids, peptides, and proteins)
Rabbits
metabolism
lipoprotein[a]
Lipoprotein
Subjects
Details
- Language :
- English
- ISSN :
- 00222275
- Volume :
- 41
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of Lipid Research
- Accession number :
- edsair.doi.dedup.....8b02dc2fbfdc0c4e7ab430c06a419a4a