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Publication : Contrasting in vivo effects of murine and human apolipoprotein A-II. Role of monomer versus dimer.

First Author  Gong EL Year  1996
Journal  J Biol Chem Volume  271
Issue  11 Pages  5984-7
PubMed ID  8626380 Mgi Jnum  J:92458
Mgi Id  MGI:3052813 Doi  10.1074/jbc.271.11.5984
Citation  Gong EL, et al. (1996) Contrasting in vivo effects of murine and human apolipoprotein A-II. Role of monomer versus dimer. J Biol Chem 271(11):5984-7
abstractText  The role of apolipoprotein A-II (apoA-II) in high density lipoprotein (HDL) structure and metabolism has been studied previously in transgenic mice overexpressing either human or murine apoA-II. These studies have shown differences between these two groups of transgenic animals in the levels of very low density, low density, and high density lipoproteins, in the HDL particle size distribution, and in the relationship between apoA-II levels and lipoprotein levels. To determine whether these differences are due to the fact that human apoA-II is dimeric and murine apoA-II monomeric, we have examined the effects of monomeric human apoA-II (hA-IImon) in transgenic mice. Site-directed mutagenesis (Cys6 -> Ser) was used to generate 15 transgenic founder lines of hA-IImon mice, that contained plasma hA-IImon concentrations over a 10-fold range (11 mg/dl to 185 mg/dl). The hA-IImon floated in the d < or = 1.21 g/ml fraction and migrated as an apoA-II monomer by nonreducing SDS-polyacrylamide gel electrophoresis. HDL levels were not correlated with hA-IImon levels (r = -0.26); HDL particle size and size distribution, as well as very low density and low density lipoprotein levels and sizes, were unchanged compared to nontransgenic control mice. These results suggest that differences between mice overexpressing human dimeric apoA-II and those overexpressing murine apoA-II are the result of sequence differences between these two apoA-II molecules and are not solely due to the fact that human apoA-II exists as a dimer.
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