Genetic analysis of LDL receptor-related genes

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The low density lipoprotein (LDL) receplor gene family consists of a growing number of structurally closely related endocytic cell surface receptors. Several members of the family are multifunctional and bind a variety of biologically diverse ligands including lipoproteins, enzymes involved in lipid metabolism, active proteases and protease inhibitors. Two family members which exhibit the hroadest ligand recognition specificity, the LI)L receptor-related l)rotein (LRP) and its close homologue gp330/megalin, are required for normal embryonic development. LRP-deficient embryos and newborn gp330/megalindeficient mice suffer from multiple pleiotropic abnormalities which makes it difficult to define the physiological roles of these receptors during development or post-natal life. To better define and dissect specific functions of the LRP in vivo we have employed tissue-specific and inducible gene targeting methods in mice. Somatic disruption of the LRP gene in hepatocytes has allowed us to unequivocally define an alternative, LI)I, receptor-independen! cholesterol clearance pathway in the liver. Experiments aiming at the disruption of the gene in other tissues and cell types, e.g. the vascular wall and neurons, are currently ongoing.

Original languageEnglish (US)
Pages (from-to)A1452
JournalFASEB Journal
Issue number9
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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