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ATP-binding cassette (ABC) transporters are transmembrane proteins found at these barriers and function to efflux xenobiotics and maintain chemical homeostasis. Despite the plethora of <jats:italic>ex vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> data showing the function and expression of ABC transporters, no imaging modality exists to study ABC transporter activity <jats:italic>in vivo<\/jats:italic> at the BPB. In the present study, we show that <jats:italic>in vitro<\/jats:italic> models of the placenta possess ABCG2 activity and can specifically transport D-luciferin, the endogenous substrate of firefly luciferase. To test ABCG2 transport activity at the BPB, we devised a breeding strategy to generate a bioluminescent pregnant mouse model to demonstrate transporter function <jats:italic>in vivo.<\/jats:italic> We found that coadministering the ABCG2 inhibitors Ko143 and gefitinib with D-luciferin increased bioluminescent signal from fetuses and placentae, whereas the control P-gp inhibitor DCPQ had no effect. We believe that our bioluminescent pregnant mouse model will facilitate greater understanding of the BPB and ABCG2 activity in health and disease.<\/jats:p>","DOI":"10.1038\/srep20418","type":"journal-article","created":{"date-parts":[[2016,2,8]],"date-time":"2016-02-08T10:50:47Z","timestamp":1454928647000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bioluminescent imaging of ABCG2 efflux activity at the blood-placenta barrier"],"prefix":"10.1038","volume":"6","author":[{"given":"Jeyan S.","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bih-Rong","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Madigan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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