Gender‐Specific Multidrug‐Resistance Transporter Expression in Choroid Plexus

Abstract

Multidrug efflux transporters of the ATP‐Binding cassette (ABC) family, ABCC1 (Mrp1) and ABCC4 (Mrp4) located on the basolateral membrane of the CP, play important roles in clearing the brain of unwanted substances and protecting it from potentially harmful material in the circulation. Previous research has shown gender‐specific patterns and compensatory responses in liver and kidney. However, little is known about the gender differences and their function in brain. In the present study we examine Mrp1 and Mrp4 mRNA expression in CP using a Mrp4 knockout mouse (Mrp4‐/‐) model and also investigate whether Abcc transporters are expressed in a gender dependent pattern as in kidney and liver. We hypothesized that the female predominant Mrp1 and Mrp4 expression will remain in CP and that in the absence of Mrp4, the activity of Mrp1 will increase. qPCR and immunoblot analysis showed that Mrp4 mRNA and protein are expressed at much higher levels in the female than in male CP. Immunoblot analysis on CP of Mrp4‐/‐ mice showed higher protein expression of Mrp1 in males supporting our hypothesis that the activity of the Mrp1 would increase. Abcc transporters share a wide variety of substrates: therefore, compensation by Mrp1 in the absence of Mrp4 and gender divergent transporter expression could manifest in differential disposition of endogenous substrates, toxicants, and therapeutic drugs, from the CSF to the blood. These sex‐specific differences in the CP highlight the need to evaluate sex differences in neurological disorders, especially those that differ in prevalence and symptoms between men and women.