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High level expression of human apolipoprotein A-I in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein A-I

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Abstract

To examine the consequences of increased apolipoprotein A-I production on cholesterol and lipoprotein metabolism, we have produced two lines of transgenic rats; one expressing moderate and one very high levels of human apolipoprotein A-I. The rats were produced by microinjection of a 13 kbp DNA fragment containing the human apolipoprotein A-I gene plus 10 kbp of its 5′ flanking sequence and 1 kbp of its 3′ flanking sequence. Both lines of transgenic rats express human apolipoprotein A-I mRNA in liver and human apolipoprotein A-I in plasma. Sera from these rats contain significantly higher levels of total apolipoprotein A-I, high density lipoprotein cholesterol and phospholipid than sera from non-transgenic littermates. Transgenic rats expressing high levels of human apolipoprotein A-I have reduced levels of serum rat apolipoprotein A-I suggesting a mechanism exists to down-regulate apolipoprotein A-I production. These transgenic rats provide a unique animal model to examine the effects of increased apolipoprotein A-I production on lipid and lipoprotein metabolism.

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Author notes

  1. Marke E. Swanson

    Present address: DNX Inc., 303B College Road East, 08540, Princeton, NJ, USA

Authors and Affiliations

  1. Department of Molecular Biology, Sandoz Research Institute, 59 Route 10, 07936, East Hanover, NJ, USA

    Marke E. Swanson & Irene St Denny

  2. Department of Lipoprotein Metabolism, Sandoz Research Institute, 59 Route 10, 07936, East Hanover, NJ, USA

    Thomas E. Hughes, Dennis S. France & James R. Paterniti Jr

  3. Preclinical Research, Sandoz Ltd, CH-4002, Basel, Switzerland

    Carlo Tapparelli, Patrick Gfeller & Kurt Bürki

Authors
  1. Marke E. Swanson
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  2. Thomas E. Hughes
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  3. Irene St Denny
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  4. Dennis S. France
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  5. James R. Paterniti Jr
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  6. Carlo Tapparelli
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  7. Patrick Gfeller
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  8. Kurt Bürki
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Swanson, M.E., Hughes, T.E., Denny, I.S. et al. High level expression of human apolipoprotein A-I in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein A-I. Transgenic Research 1, 142–147 (1992). https://doi.org/10.1007/BF02528779

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  • DOI: https://doi.org/10.1007/BF02528779

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