Abstract 229: Development of a Conditional Knockout of Cholesterol Synthesis in the Mouse
Dhcr24 (3β-hydroxysteroid-Δ24 reductase) is responsible for reducing the C24-C25 double bond in sterol intermediates of cholesterol and this step is necessary to synthesize cholesterol. In humans, mutations in the Dhcr24 gene cause desmosterolosis (OMIM #602398), characterized by severe developmental abnormalities and elevated levels of desmosterol in plasma and tissue. The first case was reported in 1998 when a premature infant died shortly after birth, had elevated levels of desmosterol and phenotypic abnormalities. Although initially reported as a ‘cholesterol-free mouse’ in Science, the global Dhcr24 knockout mouse shows neonatal lethality within 10h of birth, a finding reproduced in many different laboratories, despite sharing the original knockout mouse.
We now report a conditional knockout model using the LoxP-cre deletion system and show proof-of-principle by studying effects Dhcr24 deletion in the liver.
Author Disclosures: R. Weerasekera: None. A. McKenzie: None. J. Emmer: None. Y. Cai: None. K. Patel: None. R. Tyshynsky: None. S.B. Patel: None.
- © 2014 by American Heart Association, Inc.