Impact of liver-specific deletion of Dhcr24 gene on tissue gene expression

Genetic loss of the enzyme 3ß-hydroxysterol-∆24 reductase (DHCR24) results in Desmosterolosis (MIM #602398), a rare disease that presents with multiple congenital anomalies. Earlier studies to create a Dhcr24 global knockout mouse have failed as the pups died within 24 h of birth from lethal dermopathy. We generated a conditional knockout mouse model (Dhcr24flx/flx) and validated it by creating a liver-specific knockout Dhcr24flx/flx, Alb-Cre mouse using a mouse expressing cre recombinase driven by the albumin promoter. Despite increased circulatory and liver desmosterol due to loss of cholesterol synthesis in the liver, these mice demonstrated no marked changes in growth, fertility, hepatic architecture, lipoprotein secretion, etc. RNA-Seq analysis of the female mouse liver revealed no notable perturbations in pathways participating in cholesterol biosynthesis. RNA was isolated from liver, adrenal and macrophage of 1 mouse in each group. KO mouse from each sex were compared to floxed Cre negative control mouse of the same sex.