In the absence of a downstream element, the apolipoprotein E gene is expressed at high levels in kidneys of transgenic mice.
Human apolipoprotein (apo) E gene constructs with 30 or 5 kilobases of 5'-flanking and 1.5 kilobases of 3'-flanking regions were used to create transgenic mice. High levels of human apoE mRNA were present in the transgenic kidney, but none was detected in the liver, which is normally the major source of apoE. When a construct with 5 kilobases of 5'- and 23 kilobases of 3'-flanking regions was used, only trace levels of human apoE mRNA were detected in the kidney, whereas high levels were found in the liver. These results indicated that regulatory elements downstream of the human apoE gene interacted with the transcription initiation complex to stimulate gene expression in the liver while suppressing expression in the kidney. In each case, human apoE was secreted into the plasma. The source of human apoE in the transgenic kidney was the epithelial cells lining the proximal tubule and Bowman's capsule.
Simonet
W S
WS
Gladstone Foundation Laboratories for Cardiovascular Disease, University of California, San Francisco 94140-0608.
Bucay
N
N
Lauer
S J
SJ
Wirak
D O
DO
Stevens
M E
ME
Weisgraber
K H
KH
Pitas
R E
RE
Taylor
J M
JM
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D003001:Cloning, Molecular; D004274:DNA, Recombinant; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009693:Nucleic Acid Hybridization; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid; D012867:Skin / Q000032:analysis; D013737:Testis / Q000032:analysis; D014018:Tissue Distribution; D014158:Transcription, Genetic
D001057:Apolipoproteins E; D004274:DNA, Recombinant; D015347:RNA Probes; D012333:RNA, Messenger