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This research aims to investigate hypercholesterolemia in LDL receptor knockout mice and explore gene therapy as a reversal method.

Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery.

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This research aims to investigate hypercholesterolemia in LDL receptor knockout mice and explore gene therapy as a reversal method.
Created LDL receptor knockout mice using homologous recombination in embryonic stem cells.
Administered a recombinant adenovirus encoding the human LDL receptor to evaluate cholesterol level reversal.
Measured plasma cholesterol levels, particle size, and receptor activity after gene delivery.
LDLR-/- mice exhibited total plasma cholesterol levels twofold higher than wild-type mice.
Adenovirus delivery normalized elevated IDL and LDL levels within 4 days, restoring LDL receptor function.
Increased clearance of 125I-VLDL in treated LDLR-/- mice confirmed gene therapy efficacy.

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Randomized trial reveals gene therapy reduces cholesterol levels in hypercholesterolemic mice, indicating potential for treatment.

Ishibashi et al. (1993) studied this question.

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