Developmental abnormalities in mouse embryos lacking the HDL receptor SR-BI
Developmental abnormalities in mouse embryos lacking the HDL receptor SR-BI
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DOI：
10.1093/hmg/dds510
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发表时间：
2013-03-15
影响因子：
3.5
通讯作者：
Busso, Dolores
中科院分区：
文献类型：
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作者：
Guillermo Santander, Nicolas;Contreras-Duarte, Susana;Busso, Dolores
SRBI基因编码一种与高密度脂蛋白具有高亲和力的脂蛋白受体，主要在肝脏和类固醇生成组织中表达。老鼠体内这种基因的破坏和人类体内的突变会导致脂蛋白新陈代谢和/或生育能力的改变。在小鼠的发育过程中，清道夫受体B类成员I(SR-BI)存在于卵黄囊和胎盘中，并且只在妊娠后期的胚胎中表达。在人类中，已在滋养层细胞和胎盘中检测到它。尽管杂合子杂交获得的携带SR-BI零突变的小鼠的比例低于孟德尔比率的预期，表明该受体参与了宫内发育，但这种死亡的原因仍不清楚。在这项工作中，我们表明，缺乏SR-BI的胚胎表现出高发病率的脑外畸形，并对女性有性别偏见。免疫定位研究证实，SR-BI在发育早期不在胚胎中表达，并允许更详细地描述其在调节母婴营养物质转运的细胞中的定位。与野生型相比，SR-BI缺失型胚胎含有较少的胆固醇，提示SR-BI参与了母胎胆固醇的转运。新生儿SR-BI缺陷幼鼠表现出宫内生长受限，这表明该受体对胎儿生长也很重要。总之，我们的工作结果表明，胚胎外组织中SR-BI的存在参与了胆固醇和/或其他脂质的母胎运输，并在神经管关闭和胎儿生长过程中发挥了作用。
The srbi gene encodes a lipoprotein receptor with high affinity for high density lipoprotein that is mainly expressed in the liver and in steroidogenic tissues. Disruption of this gene in mice and mutations in humans lead to alterations in lipoprotein metabolism and/or fertility. During murine development, scavenger receptor class B member I (SR-BI) is present in the yolk sac and the placenta and is only expressed in the embryo itself late in gestation. In humans, it has been detected in trophoblast cells and placenta. Although the proportion of mice carrying a null mutation in SR-BI obtained from heterozygous inter-crosses is lower than the expected by the Mendelian ratio, suggesting the involvement of this receptor in intrauterine development, the cause of this demise has remained unknown. In this work, we show that embryos lacking SR-BI exhibit a high prevalence of exencephaly with a sex bias toward females. Immunolocalization studies confirmed that SR-BI is not expressed in the embryo at early stages of development and allowed a more detailed description of its localization in the cells that mediate maternal-fetal transport of nutrients. SR-BI-null embryos contain less cholesterol than their wild-type littermates, suggesting the involvement of SR-BI in materno-fetal cholesterol transport. Newborn SR-BI-deficient pups exhibit intrauterine growth restriction, suggesting that this receptor is also important for fetal growth. Altogether, the results of our work suggest that the presence of SR-BI in extraembryonic tissues is involved in the maternal-fetal transport of cholesterol and/or other lipids with a role during neural tube closure and fetal growth.