Genetic analysis of digestive physiology using fluorescent phospholipid reporters.
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.
Farber
S A
SA
Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210, USA. sfarber@lac.jci.tju.edu
Pack
M
M
Ho
S Y
SY
Johnson
I D
ID
Wagner
D S
DS
Dosch
R
R
Mullins
M C
MC
Hendrickson
H S
HS
Hendrickson
E K
EK
Halpern
M E
ME
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D001647:Bile Acids and Salts / Q000494:pharmacology; D001896:Boron Compounds / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004068:Digestive System Physiological Phenomena / Q000187:drug effects; D005456:Fluorescent Dyes / Q000378:metabolism*; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009154:Mutation / Q000235:genetics; D010743:Phospholipids / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D001896:Boron Compounds; D005456:Fluorescent Dyes; D006538:Heptanoic Acids; D010743:Phospholipids; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin; D008049:Lipase