Generation and validation of a conditional knockout mouse model for desmosterolosis.

ABSTRACT: The enzyme 3β-hydroxysterol-Δ24 reductase (DHCR24, EC 1.3.1.72) catalyzes the conversion of desmosterol to cholesterol and is obligatory for post-squalene cholesterol synthesis. Genetic loss of this enzyme results in desmosterolosis (MIM #602398), a rare disease that presents with multiple congenital anomalies, features of which overlap with subjects with the Smith-Lemli-Opitz syndrome (another post-squalene cholesterol disorder). Global knockout (KO) of Dhcr24 in mice recapitulates the biochemical phenotype, but pups die within 24 h from a lethal dermopathy, limiting its utility as a disease model. Here, we report a conditional KO mouse model (Dhcr24^flx/flx) and validate it by generating a liver-specific KO (Dhcr24^{flx/flx,Alb-Cre}). Dhcr24^{flx/flx,Alb-Cre} mi

SUBMITTER: Kanuri B 

PROVIDER: S-EPMC7933790 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature