Faculty Collaboration Database

Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz syndrome mouse. Mol Genet Metab 2007 May;91(1):7-14

Date

01/02/2007

Pubmed ID

17197219

Pubmed Central ID

PMC1852500

DOI

10.1016/j.ymgme.2006.11.009

Scopus ID

2-s2.0-34047251013 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

The Smith-Lemli-Opitz syndrome (SLOS) is caused by a genetic defect in cholesterol biosynthesis; mutations in the enzyme 3ss-hydroxysterol Delta7 reductase (Dhcr7) lead to a failure of cholesterol (and desmosterol) synthesis, with an accumulation of precursor sterols, such as 7-dehydrocholesterol. Extensive genotype-phenotype analyses have indicated that there is considerable variation in the severity of the disease, much of which is not explained by defects in the Dhcr7 gene alone. Factors ranging from variations in maternal-fetal cholesterol transfer during pregnancy, to other genetic factors have been proposed to account for this variability. Variations at the APOE locus affect plasma cholesterol levels in humans and this polymorphic gene has been found to be associated with cardiovascular as well as neurological disorders. This locus has recently been implicated in accounting for some of the variations in SLOS. To address whether maternal hypercholesterolemia can affect fetal outcome, we tested the ability of maternal hypercholesterolemia to rescue the neonatal lethality in a mouse model of SLOS. Maternal hypercholesterolemia, induced by ApoE or Ldl-r deficiency not only failed to ameliorate the postnatal lethality, it increased the prenatal mortality of Dhcr7 deficient pups. Thus the murine data suggest that maternal loss of ApoE or Ldl-r function further exacerbates the neonatal lethality, suggesting they may play a role in maternal transfer of cholesterol to the embryo.

Author List

Solcà C, Pandit B, Yu H, Tint GS, Patel SB

Author

Hongwei Yu MD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Apolipoproteins E
Brain
Cholesterol
Embryo, Mammalian
Female
Genes, Lethal
Genotype
Humans
Liver
Lung
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pregnancy
Smith-Lemli-Opitz Syndrome
Triglycerides