Choroid plexus transport: gene deletion studies

Choroid plexus (CP) epithelial cells and their linking tight junctions form the blood-CSF barrier (along with the arachnoid membrane) and are the primary site of CSF secretion. As with the cerebral endothelium, the site of the blood-brain barrier (BBB), the CP epithelium possesses a wide variety of transporters [1-4]. CP transporters are involved in cell and CSF homeostasis, the movement of nutrients into and waste products out of the CSF, and CSF secretion. In addition, as ependymal cells are not linked by tight junctions, CP transport may impact periventricular brain regions and potentially deeper structures by affecting CSF composition.It is important to identify which transporters are present at the CP and their role (physiological and potentially therapeutic). However, the latter is complicated by the array of transporters present, overlapping substrate specificity and often a lack of specific inhibitors. One approach that has proven useful in transporter studies is the use of animals with gene deletions (e.g. KO mice) or gene mutations (functional knockouts). This approach has been used extensively in BBB studies to examine the role of different ATP-binding cassette (ABC) transporters in drug efflux (e.g. [5-8]). Multidrug resistance protein [MDR], breast cancer related protein [BCRP] and multidrug resistance associated proteins [MRPs] are all present at the BBB and have considerable substrate overlap. In comparison, relatively few CP transport studies have employed KO animals. This paper reviews those studies and the insights they give on CP transport and the relative functions of the blood-CSF and the blood brain barriers. It also discusses some methodological considerations when performing such studies. This paper does not aim to review the production of KO (and transgenic) mice.Multiple transporter KO mice have been generated. For example, there have been BBB transport studies on KO mice for Abcb1 (P-glycoprotein; Mdr1; [7]), Abcg2 (breast cancer related p