Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy of sebaceous and meibomian glands and depletion of wax esters in the eyelid

Stearoyl-CoA desaturase (SCD) is a microsomal rate-limiting enzyme in the c ellular synthesis of monounsaturated fatty acids (MUFA), mainly oleate (18: 1) and palmitoleate (16:1), which are the major MUFA of membrane phospholip ids, cholesterol esters and triglycerides. Three well-characterized isoform s of SCD, SCD1, SCD2 and SCD3, exist in mice. To investigate the physiologi c functions of SCD1, we generated SCD1 null (SCD1 -/-) mice. The skin and e yelid of SCD1 -/- mice are deficient in triglycerides and cholesterol ester s, and the eyelid also is deficient in wax esters. Furthermore, the eyelid and skin of SCD1 -/- mice have higher levels of free cholesterol. SCD1 -/- mice develop cutaneous abnormalities and narrow eye fissure with atrophic s ebaceous and meibomian glands. Consumption of diets containing high levels of oleate, failed to restore the levels of triglycerides, cholesterol ester s and wax esters in SCD1 -/- mice to the levels found in the eyelid of wild -type mice. These results reveal a physiologic role of SCD in cholesterol h omeostasis as well as in the de novo biosynthesis of cholesterol esters, tr iglycerides and wax esters required for normal skin and eyelid function.