title: The Bulk of Autotaxin Activity Is Dispensable for Adult Mouse Life.
abstract: Autotaxin (ATX, Enpp2) is a secreted lysophospholipase D catalysing the production of lysophosphatidic acid, a pleiotropic growth factor-like lysophospholipid. Increased ATX expression has been detected in a number of chronic inflammatory diseases and different types of cancer, while genetic interventions have proven a role for ATX in disease pathogenesis. Therefore, ATX has emerged as a potential drug target and a large number of ATX inhibitors have been developed exhibiting promising therapeutic potential. However, the embryonic lethality of ATX null mice and the ubiquitous expression of ATX and LPA receptors in adult life question the suitability of ATX as a drug target. Here we show that inducible, ubiquitous genetic deletion of ATX in adult mice, as well as long-term potent pharmacologic inhibition, are well tolerated, alleviating potential toxicity concerns of ATX therapeutic targeting.
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Katsifa
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Eleanna
authors.initials: E
authors.lastname: Kaffe
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Nefeli
authors.initials: N
authors.lastname: Nikolaidou-Katsaridou
authors.affiliation: Genome Engineering Technologies Group and Skeletal Diseases TFA Group, Regeneron Pharmaceuticals Inc., Tarrytown, New York, United States of America.
authors.forename: Aris N
authors.initials: AN
authors.lastname: Economides
authors.affiliation: Physiology and Experimental Medicine Research Program, the Hospital for Sick Children, Center for Phenogenomics, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Newbigging
authors.affiliation: Physiology and Experimental Medicine Research Program, the Hospital for Sick Children, Center for Phenogenomics, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Colin
authors.initials: C
authors.lastname: McKerlie
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Aidinis
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019426:Integrases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010727:Phosphoric Diester Hydrolases / Q000097:blood / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D000099189:Lysophospholipase D
chemical_list: D001583:Benzoxazoles; D019426:Integrases; D010727:Phosphoric Diester Hydrolases; D010879:Piperazines; D013629:Tamoxifen; D000099189:Lysophospholipase D; C550725:6-(3-(piperazin-1-yl)propanoyl)benzo(d)oxazol-2(3H)-one; C045073:Cre recombinase