Key result
Mice humanized with APOB knockout human hepatocytes successfully model human hypobetalipoproteinemia and lipid disorders.
Why the study?
Differences in lipoprotein metabolism between mice and humans make it difficult to model disorders of human lipid metabolism in transgenic mice.
Human lipid metabolism disorders can be successfully modeled in liver chimeric mice using human knockout hepatocytes.
No immediate clinical implications; leaves open utility of humanized models for lipid disorder research.
Lipoprotein metabolism is significantly different between mice and humans thus making it difficult to model disorders of human lipid metabolism in transgenic mice. Systemic lipoprotein metabolism is predominantly governed by hepatocytes, and mice with humanized livers display human-like lipid profiles. Here we report a highly efficient method to knock out genes in human hepatocytes while retaining their ability to repopulate immune deficient rodents. As proof-of-principle Fah deficient, immune compromised mice were repopulated with Apolipoprotein B (APOB) knockout human hepatocytes. Mice humanized with knockout cells recapitulated typical features of human hypobetalipoproteinemia. We conclude that at least some human lipid metabolism disorders can be modeled in liver chimeric mice using human knockout hepatocytes.
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Tiyaboonchai et al. (2026) studied Hypobetalipoproteinemia. Repopulation with Apolipoprotein B (APOB) knockout human hepatocytes was evaluated on Recapitulation of typical features of human hypobetalipoproteinemia. Mice humanized with APOB knockout human hepatocytes successfully recapitulated typical features of human hypobetalipoproteinemia, demonstrating a novel method to model human lipid metabolism disorders.
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