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 m...

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Bibliographic Details
Published in:The Journal of biological chemistry 1990-07, Vol.265 (19), p.10809-10812
Main Authors: SIMONET, W. S, BUCAY, N, LAUER, S. J, WIRAK, D. O, STEVENS, M. E, WEISGRABER, K. H, PITAS, R. E, TAYLOR, J. M
Format: Article
Language:English
Subjects:
Animals
Apolipoproteins E - genetics
Biological and medical sciences
Cloning, Molecular
DNA, Recombinant
enhancers
Fundamental and applied biological sciences. Psychology
Gene Expression
genes
Humans
Immunoenzyme Techniques
kidney
Kidney - metabolism
Liver - metabolism
Male
Mice
Mice, Inbred ICR
Mice, Transgenic
Molecular and cellular biology
Molecular genetics
Nucleic Acid Hybridization
Regulatory Sequences, Nucleic Acid
RNA Probes
RNA, Messenger - analysis
Skin - analysis
Testis - analysis
Tissue Distribution
Transcription, Genetic
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(19)38516-3