Targeted deletion of fatty acid transport protein-4 results in early embryonic lethality.
Fatty acid transport protein-4 (FATP4) is the major FATP in the small intestine. We previously demonstrated, using in vitro antisense experiments, that FATP4 is required for fatty acid uptake into intestinal epithelial cells. To further examine the physiological role of FATP4, mice carrying a targeted deletion of FATP4 were generated. Deletion of one allele of FATP4 resulted in 48% reduction of FATP4 protein levels and a 40% reduction of fatty acid uptake by isolated enterocytes. However, loss of one FATP4 allele did not cause any detectable effects on fat absorption on either a normal or a high fat diet. Deletion of both FATP4 alleles resulted in embryonic lethality as crosses between heterozygous FATP4 parents resulted in no homozygous offspring; furthermore, no homozygous embryos were detected as early as day 9.5 of gestation. Early embryonic lethality has been observed with deletion of other genes involved in lipid absorption in the small intestine, namely microsomal triglyceride transfer protein and apolipoprotein B, and has been attributed to a requirement for fat absorption early in embryonic development across the visceral endoderm. In mice, the extraembryonic endoderm supplies nutrients to the embryo prior to development of a chorioallantoic placenta. In wild-type mice we found that FATP4 protein is highly expressed by the epithelial cells of the visceral endoderm and localized to the brush-border membrane of extraembryonic endodermal cells. This localization is consistent with a role for FATP4 in fat absorption in early embryogenesis and suggests a novel requirement for FATP4 function during development.
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D050612:Fatty Acid Transport Proteins; D005260:Female; D005313:Fetal Death / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D005804:Genes, Lethal; D006579:Heterozygote; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D013347:Subcellular Fractions / Q000378:metabolism
D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C493572:Slc27a4 protein, mouse