Lipid metabolism in zebrafish.
Forward genetics is an unbiased methodology to discover new genes or functions of genes. At the present, the zebrafish is one of the few vertebrate systems where large-scale forward genetic studies are practical. Fluorescent lipid labeling of zebrafish larvae derived from families created from ENU-mutagenized fish enabled us to perform a large scale in vivo screen to identify mutants with perturbed lipid processing. With the aid of the zebrafish genome project, positional cloning of mutated genes with abnormal lipid metabolism can be accelerated. MO- and gripNA-based transient gene silencing is feasible in zebrafish embryos and provides a reverse genetic screening strategy to search for important lipid regulators. The advantages of using zebrafish as a vertebrate model to study lipid metabolism include its rapid external development and its optical clarity that enables the monitoring of biological processes. Large scale, high-throughput drug screening in vivo, especially for drugs that inhibit lipid absorption, can be easily achieved in this model. These zebrafish-based assays are important tools to understand aspects of lipid biology with significant clinical implications.
Ho
Shiu-Ying
SY
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Thorpe
Juanita L
JL
Deng
Yun
Y
Santana
Evelyn
E
DeRose
Robert A
RA
Farber
Steven A
SA
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism; D000069059:Atorvastatin; D001384:Azetidines / Q000494:pharmacology; D001896:Boron Compounds / Q000737:chemistry; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004224:Diterpenes / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D005038:Ethylnitrosourea / Q000494:pharmacology; D000069438:Ezetimibe; D005204:Farnesol / Q000494:pharmacology; D051231:Farnesyltranstransferase; D051228:Geranyltranstransferase; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017368:Protein Prenylation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; C077527:7-nitrobenz-2-oxa-1,3-diazol-4-ylcholesterol; D017306:Annexin A2; D001384:Azetidines; D001896:Boron Compounds; D051242:Caveolin 1; D022461:Caveolins; D004224:Diterpenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D010714:Phosphatidylethanolamines; D011758:Pyrroles; C483858:phosphatidylethanolamine; D005204:Farnesol; D004247:DNA; D002784:Cholesterol; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; C017338:geranylgeraniol; D019883:Alkyl and Aryl Transferases; D051228:Geranyltranstransferase; D051231:Farnesyltranstransferase; D000069438:Ezetimibe; D009327:4-Chloro-7-nitrobenzofurazan; D005038:Ethylnitrosourea; D008798:Mevalonic Acid