Regulation of the human apolipoprotein AIV gene expression in transgenic mice

FEBS Letters

Ochoa, A¹  Zakin, M.M¹  Baralle, F.E²  Baralle, M²  Muro, A.F²  Vergnes, L¹ 

[1] Unité d'Expression des Gènes Eucaryotes, Institut Pasteur, 28 rue du Dr. Roux, Paris, France;Molecular Pathology, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy

关键词: Apolipoprotein AI-CIII-AIV;    Quantitative polymerase chain reaction;    Tissue specificity;    Intestine;    Liver;    Regulation;    Transgenic mouse;    Apo;    apolipoprotein;    wt;    wild type;   

DOI  :  10.1016/S0014-5793(99)00096-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The apolipoprotein (Apo) AI-CIII-AIV gene cluster has a complex pattern of gene expression that is modulated by both gene- and cluster-specific cis-acting elements. In particular the regulation of Apo AIV expression has been previously studied in vivo and in vitro including several transgenic mouse lines but a complete, consistent picture of the tissue-specific controls is still missing. We have analysed the role of the Apo AIV 3′ flanking sequences in the regulation of gene expression using both in vitro and in vivo systems including three lines of transgenic mice. The transgene consisted of a human fragment containing 7 kb of the 5′ flanking region, the Apo AIV gene itself and 6 kb of the 3′ flanking region (−7+6 Apo AIV). Accurate analysis of the Apo AIV mRNA levels using quantitative PCR and Northern blots showed that the −7+6 kb Apo AIV fragment confers liver-specific regulation in that the human Apo AIV transgene is expressed at approximately the same level as the endogenous mouse Apo AIV gene. In contrast, the intestinal regulation of the transgene did not follow the pattern observed with the endogenous gene although it produced a much higher intestinal expression following the accepted human pattern. Therefore, this animal model provides an excellent substrate to design therapeutic protocols for those metabolic derangements that may benefit from variations in Apo AIV levels and its anti-atherogenic effect.

【 授权许可】

Unknown