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| Inducible inactivation of hepatic LRP gene by Cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants |
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| Author(s): Rohlmann A, Gotthardt M, Hammer RE, Herz J |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 101 Issue: 3 Pages: 689-695 Published: FEB 1 1998 |
| Times Cited: 222 References: 31 |
| Abstract: The multifunctional low density lipoprotein (LDL) receptor-related protein (LRP) has been postulated to participate in a number of diverse physiological and pathological processes ranging from the homeostasis of plasma lipoproteins, atherosclerosis, and fibrinolysis to neuronal regeneration and survival. It has not been possible to demonstrate in vivo the physiological significance of LRP for each of these complex processes by a conventional gene knockout approach because LRP is essential for embryonic development. Here we have used the Cre/loxP recombination system to achieve inducible, tissue-specific and quantitative disruption of the LRP gene in adult mice, Inactivation of LRP in the livers of LDL receptor-deficient mice resulted in the accumulation of cholesterol-rich remnant lipoproteins in the circulation. In normal animals, this caused a compensatory upregulation of the LDL receptor in the liver, Conditional gene targeting has thus allowed us to isolate a specific physiological function of LRP for in vivo analysis and has provided unequivocal evidence for another LDL receptor-independent cholesterol clearance pathway in liver. |
| Document Type: Article |
| Language: English |
| Reprint Address: Herz, J (reprint author), Univ Texas, SW Med Ctr, Dept Mol Genet, Howard Hughes Med Inst, 5323 Harry Hines Blvd, Dallas, TX 75235 USA |
Addresses:
1. Univ Texas, SW Med Ctr, Dept Mol Genet, Howard Hughes Med Inst, Dallas, TX 75235 USA
2. Univ Texas, SW Med Ctr, Dept Biochem, Howard Hughes Med Inst, Dallas, TX 75235 USA
3. Max Delbruck Ctr Mol Med, Berlin, Germany |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: YW195 |
| ISSN: 0021-9738 |
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