{"title":"恒河猴自发性少原性突变诱导的高胆固醇血症","authors":"Akiko Takenaka, Juri Suzuki, Hiroyuki Tanaka, Kumiko Hibino, Yoshiro Kamanaka, Shin Nakamura, Fusako Mitsunaga, Yoshi Kawamoto, Mayumi Morimoto, Seitaro Aisu, Takayoshi Natsume","doi":"10.1111/jmp.12642","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Activity of low-density lipoprotein receptor (LDLR), plasma CH levels and mRNA expression levels of <i>LDLR</i> were measured after administration of 0.1% (0.27 mg/kcal) or 0.3% CH.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Activity of <i>p</i>. (<i>Cys82Tyr</i>) of LDLR was 71% and 42% in the heterozygotes and a homozygote, respectively. The mRNA expression level of <i>LDLR</i> in the <i>p</i>. (<i>Val241Ile</i>) of membrane-bound transcription factor protease, site 2 (<i>MBTPS2</i>, S2P protein) was 0.83 times lower than normal levels. <i>LDLR</i> 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Oligogenic mutations of <i>p</i>. (<i>Cys82Tyr</i>) in <i>LDLR</i> and <i>p</i>. (<i>Val241Ile</i>) in <i>MBTPS2</i> (S2P) caused hypercholesterolemia exceeding cardiovascular risk levels under a 0.1% CH diet.</p>\n </section>\n </div>","PeriodicalId":16439,"journal":{"name":"Journal of Medical Primatology","volume":"52 4","pages":"230-243"},"PeriodicalIF":0.8000,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jmp.12642","citationCount":"0","resultStr":"{\"title\":\"Hypercholesterolemia induced by spontaneous oligogenic mutations in rhesus macaques (Macaca mulatta)\",\"authors\":\"Akiko Takenaka, Juri Suzuki, Hiroyuki Tanaka, Kumiko Hibino, Yoshiro Kamanaka, Shin Nakamura, Fusako Mitsunaga, Yoshi Kawamoto, Mayumi Morimoto, Seitaro Aisu, Takayoshi Natsume\",\"doi\":\"10.1111/jmp.12642\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Activity of low-density lipoprotein receptor (LDLR), plasma CH levels and mRNA expression levels of <i>LDLR</i> were measured after administration of 0.1% (0.27 mg/kcal) or 0.3% CH.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Activity of <i>p</i>. (<i>Cys82Tyr</i>) of LDLR was 71% and 42% in the heterozygotes and a homozygote, respectively. The mRNA expression level of <i>LDLR</i> in the <i>p</i>. (<i>Val241Ile</i>) of membrane-bound transcription factor protease, site 2 (<i>MBTPS2</i>, S2P protein) was 0.83 times lower than normal levels. <i>LDLR</i> 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Oligogenic mutations of <i>p</i>. (<i>Cys82Tyr</i>) in <i>LDLR</i> and <i>p</i>. (<i>Val241Ile</i>) in <i>MBTPS2</i> (S2P) caused hypercholesterolemia exceeding cardiovascular risk levels under a 0.1% CH diet.</p>\\n </section>\\n </div>\",\"PeriodicalId\":16439,\"journal\":{\"name\":\"Journal of Medical Primatology\",\"volume\":\"52 4\",\"pages\":\"230-243\"},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2023-04-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jmp.12642\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medical Primatology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/jmp.12642\",\"RegionNum\":4,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Primatology","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jmp.12642","RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
Hypercholesterolemia induced by spontaneous oligogenic mutations in rhesus macaques (Macaca mulatta)
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.
期刊介绍：
The Journal of Medical Primatology publishes research on non-human primates as models to study, prevent, and/or treat human diseases; subjects include veterinary medicine; morphology, physiology, reproductive biology, central nervous system, and cardiovascular diseases; husbandry, handling, experimental methodology, and management of non-human primate colonies and laboratories; non-human primate wildlife management; and behaviour and sociology as related to medical conditions and captive non-human primate needs.
Published material includes: Original Manuscripts - research results; Case Reports - scientific documentation of a single clinical study; Short Papers - case histories, methodologies, and techniques of particular interest; Letters to the Editor - opinions, controversies and sporadic scientific observations; Perspectives – opinion piece about existing research on a particular topic; Minireviews – a concise review of existing literature; Book Reviews by invitation; Special Issues containing selected papers from specialized meetings; and Editorials and memoriams authored by the Editor-in-Chief.
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