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Science 18 May 2001:
Vol. 292. no. 5520, pp. 1385 - 1388
DOI: 10.1126/science.1060418
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Reports

Genetic Analysis of Digestive Physiology Using Fluorescent Phospholipid Reporters

Steven A. Farber,12*dagger ddagger Michael Pack,3*dagger Shiu-Ying Ho,2 Iain D. Johnson,5 Daniel S. Wagner,4 Roland Dosch,4 Mary C. Mullins,4 H. Stewart Hendrickson,6 Elizabeth K. Hendrickson,6 Marnie E. Halpern1

Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleavage products results in intense gall bladder fluorescence. Genetic screening identifies zebrafish mutants, such as fat free, that show normal digestive organ morphology but severely reduced phospholipid and cholesterol processing. Thus, fluorescent lipids provide a sensitive readout of lipid metabolism and are a powerful tool for identifying genes that mediate vertebrate digestive physiology.

1 Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210, USA.
2 Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
3 Department of Medicine,
4 Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
5 Molecular Probes Inc., Eugene, OR 97402, USA.
6 Department of Chemistry, University of Washington, Seattle, WA 98133, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: sfarber{at}lac.jci.tju.edu, mpack{at}mail.med.upenn.edu

ddagger    Present address: Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

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Science. ISSN 0036-8075 (print), 1095-9203 (online)