Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses
- Lawrence Berkeley Lab., CA (United States)
In Western societies high density lipoprotein (HDL) levels correlate inversely with the risk for coronary heart disease. The primary protein component of both human and mouse HDL is apolipoprotein A-I (apoAI), which comprises {gt}70% of HDL protein and 30% of HDL mass. Human HDLs include particles of several distinct size subpopulations, wheras HDLs from inbred C57BL/6 mice contain a single population of particles. To study the regulation of apoAI expression and its role in HDL assembly, we created transgenic C57BL/6 mice containing the human apoAI gene. Two independent lines of transgenic mice with approximately twice the normal plasma levels of total apoAI were studied. The level of mouse apoAI is reduced {gt}4-fold in both transgenic lines, comprising only 4% of total plasma apoAI levels in one transgenic line and 13% in the other. The authors demonstrate that the mechanism responsible for the decrease in mouse apoAI is posttranscriptional. Parallel to the replacement of mouse with human apoAI, the single HDL species normally present in the plasma of C57BL/6 is replaced by two HDL subclasses similar in size to human HDL{sub 2b} and HDL{sub 3a}. The changes in murine apolipoprotein levels and HDL subclass size are inherited by all transgenic offspring of the two founder animals. These results suggest a dominant role of apoAI in determining the HDL particle size distribution and a mechanism involving expression of human apoAI transgenes that alters the plasma levels of mouse apoAI.
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 5043770
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:2; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
APOLIPOPROTEINS
BIOCHEMISTRY
ARTERIOSCLEROSIS
GENE REGULATION
DNA
AUTORADIOGRAPHY
MAN
MICE
PHOSPHORUS 32
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARDIOVASCULAR DISEASES
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DISEASES
ISOTOPES
LIGHT NUCLEI
LIPIDS
LIPOPROTEINS
MAMMALS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
RODENTS
VASCULAR DISEASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques