Can I read Non-physiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage on EtoBox?

Non-physiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage by Guenter Cichon; Thomas Willnow; Susanne Herwig; Wolfgang Uckert; Peter Löser; Hartmut H. Schmidt; Tahar Benhidjeb; Peter M. Schlag; Frank Schnieders; Dagmara Niedzielska; Joerg Heeren is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Non-physiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage about?

## Background: Gene therapy of familial hypercholesterolemia (fh) requires successful transfer and lifelong expression of a functional low density lipoprotein receptor (ldlr) gene in the liver. most of the vector systems currently employed for gene therapy use promoter elements which do not modulate transgene expression in a physiological manner. ## Methods: To study the in vivo effects of constitutive ldlr gene expression in the absence of interfering immunological reactions we established a new mouse model which combines homozygous ldlr deficiency and severe combined immune deficiency (scid). ## Results: Adenovirus-mediated transfer and expression of the ldlr gene under the control of a commonly used virus-derived promoter (minimal cmv promoter) leads to prolonged reduction of serum cholesterol levels in ldlr-deficient scid mice. during the first 10 days after gene therapy serum cholesterol drops to about 10% of pretherapeutic values. serum cholesterol persists on this level for 2 weeks and then slowly starts to rise again. four months after vector application serum levels have reached about 40% of pretherapeutic values. however, as early as 5 days after gene transfer, the histol

Who reads Non-physiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage?

Author

Guenter Cichon; Thomas Willnow; Susanne Herwig; Wolfgang Uckert; Peter Löser; Hartmut H. Schmidt; Tahar Benhidjeb; Peter M. Schlag; Frank Schnieders; Dagmara Niedzielska; Joerg Heeren

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 1099-498X)

Published

2004

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)