Developmental abnormalities in mouse embryos lacking the HDL receptor SR-BI

Nicolás Guillermo Santander, Susana Contreras-Duarte, María Fernanda Awad, Carlos Lizama, Isabella Passalacqua, Attilio Rigotti, Dolores Busso*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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 intercrosses 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

Original languageEnglish
Pages (from-to)1086-1096
Number of pages11
JournalHuman Molecular Genetics
Volume22
Issue number6
DOIs
StatePublished - Mar 2013
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Chilean National Council for Scientific and Technological Research (CONICYT) programs Inserción de Investigadores Jóvenes en Academia (79090028 to D.B.) and Fondo Nacional del Desarrollo Científico y Tec-nológico (11090064 to D.B. and 1110712 to A.R.) and by the Summer Research Program for Medical Students from the School of Medicine, Pontificia Universidad Católica de Chile (to I.P.).

Keywords

  • Cholesterol
  • HDL receptor SR BI
  • High density lipoprotein receptor
  • Unclassified drug

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