ACCELERATED COMMUNICATION Targeted Disruption of Murine Organic Anion-Transporting Polypeptide 1b2 (oatp1b2/Slco1b2) Significantly Alters Disposition of Prototypical Drug Substrates Pravastatin and Rifampin

Organic anion-transporting polypeptides (OATP) 1B1 and 1B3 are widely acknowledged as important and rate-limiting to the hepatic uptake of many drugs in clinical use. Accordingly, to better understand the in vivo relevance of OATP1B transport-ers, targeted disruption of murine Slco1b2 gene was carried out. It is noteworthy that Slco1b2(/) mice were fertile, de-veloped normally, and exhibited no overt phenotypic abnormal-ities. We confirmed the loss of Oatp1b2 expression in liver using real-time polymerase chain reaction, Western Blot anal-ysis, and immunohistochemistry. Expression of Oatp1a4 and Oatp2b1 but not Oatp1a1 was greater in female Slco1b2(/) mice, but expression of other non-OATP transporters did not significantly differ between wild-type and Slco1b2(/) male mice. Total bilirubin level was elevated by 2-fold in th