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Updated: Jul 30, 2025
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
Hypercholesterolemia induced by spontaneous oligogenic mutations in rhesus macaques (Macaca mulatta)
Akiko Takenaka1, Juri Suzuki2, Hiroyuki Tanaka2
1Department of Health and Nutrition, Faculty of Health and Human Life, Nagoya Bunri University, Inazawa, Japan.
Background:
A rhesus macaque with the fourth highest plasma cholesterol (CH) levels of 501 breeding macaques was identified 22 years ago. Seven offspring with gene mutations causing hypercholesterolemia were obtained.
Methods:
Activity of low-density lipoprotein receptor (LDLR), plasma CH levels and mRNA expression levels of LDLR were measured after administration of 0.1% (0.27 mg/kcal) or 0.3% CH.
Results:
Activity of p. (Cys82Tyr) of LDLR was 71% and 42% in the heterozygotes and a homozygote, respectively. The mRNA expression level of LDLR in the p. (Val241Ile) of membrane-bound transcription factor protease, site 2 (MBTPS2, S2P protein) was 0.83 times lower than normal levels. LDLR mRNA levels were increased for up to 4 weeks by administration of 0.3% CH before suddenly decreasing to 80% of the baseline levels after 6 weeks.
Conclusion:
Oligogenic mutations of p. (Cys82Tyr) in LDLR and p. (Val241Ile) in MBTPS2 (S2P) caused hypercholesterolemia exceeding cardiovascular risk levels under a 0.1% CH diet.
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