PLX248371

GSE146523: The effects of liver specific deletion of Dhcr7 on gene expression

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder caused by autosomal recessive mutations in the Dhcr7 gene. SLOS patients present clinically with multiple dysmorphologies, neurological, behavioral and cognitive defects, and demonstrate impaired cholesterol biosynthesis resulting in markedly elevated 7-DHC in all bodily tissues and fluids. Previous rodent models of SLOS suffered from neonatal mortality or variation in the biochemical phenotype over time. We generated a viable murine model bearing a conditional flosed allele of the Dhcr7 gene, and validated it by generating a mice with liver-specific deletion of Dhcr7 by breeding with a strain expressing Cre recombinase driven by an albumin promoter . These mice demonstrated elevated circulatory and liver 7-DHC levels, but phenotypic characterization of the knockout mice revealed no significant changes in viability, fertility, growth curves, liver architecture, hepatic triglyceride secretion, and parameters of systemic glucose homeostasis. Investigation in to changes in the liver transcriptome were investigated withe RNAseq, and identified enrichment in various pathways, including steroid hormone biosynthesis and various cell signaling and metabolism pathways. Most notably missing from the list are the genes related to cholesterol biosynthesis. Generation of this Dhcr7 conditional knockout model will allow for better studies into the post natal effects of blocking cholesterol biosynthesis, accumulation of 7-DHC, and the role of DHCR7 in specific tissues. SOURCE: Shailendra PatelPatel University of Cincinnati