NDLI: Correction of the genetic defect in hepatocytes from the Watanabe heritable hyperlipidemic rabbit.

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Correction of the genetic defect in hepatocytes from the Watanabe heritable hyperlipidemic rabbit.

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Correction of the genetic defect in hepatocytes from the Watanabe heritable hyperlipidemic rabbit.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Johnston, D. E. Wilson, J. M. Mulligan, R. C. Jefferson, D. M.
Description	Author Affiliation: Wilson JM ( Whitehead Institute for Biomedical Research, Cambridge, MA.);
Abstract	Familial hypercholesterolemia is an inherited disease in humans that is caused by a defect in the receptor for low density lipoproteins (LDLR). The existence of an animal model for this disease, the Watanabe heritable hyperlipidemic (WHHL) rabbit, makes it an attractive candidate for developing new therapies that involve gene transfer into liver. As a first step toward the development of these therapies, we report the use of retrovirus-mediated gene transfer to correct the genetic defect in hepatocytes isolated from WHHL rabbits. A series of retroviral vectors that express the gene for human LDLR were constructed, each differing in the transcriptional elements used to drive LDLR expression. Helper-free amphotropic virus stocks representing each construct were then used to infect primary cultures of hepatocytes that were isolated from newborn WHHL rabbits. The efficiency of transduction, as measured by Southern analysis of integrated proviral sequences, ranged from 20% to 100%. Expression of human LDLR was analyzed by blot hybridization analysis of total cellular RNA and by biochemical and in situ analyses of transduced cultures for receptor function. The vector in which the expression of LDLR was driven by the viral long terminal repeat sequence produced the greatest quantity of LDLR RNA and protein in WHHL hepatocytes; LDLR activity approached normal levels in these cultures.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	12
Volume Number	85
Language	English
Publisher	National Academy of Sciences
Publisher Date	1988-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Genes Genetic Vectors Hyperlipoproteinemia Type II Genetics Liver Metabolism Receptors, LDL Retroviridae Transfection Animals Animals, Newborn Cells, Cultured DNA Disease Models, Animal Genes, Viral Cytology RNA Rabbits Beta-Galactosidase Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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