title: Autotaxin overexpression causes embryonic lethality and vascular defects.
abstract: Autotaxin (ATX) is a secretory protein, which converts lysophospholipids to lysophosphatidic acid (LPA), and is essential for embryonic vascular formation. ATX is abundantly detected in various biological fluids and its level is elevated in some pathophysiological conditions. However, the roles of elevated ATX levels remain to be elucidated. In this study, we generated conditional transgenic (Tg) mice overexpressing ATX and examined the effects of excess LPA signalling. We found that ATX overexpression in the embryonic period caused severe vascular defects and was lethal around E9.5. ATX was conditionally overexpressed in the neonatal period using the Cre/loxP system, which resulted in a marked increase in the plasma LPA level. This resulted in retinal vascular defects including abnormal vascular plexus and increased vascular regression. Our findings indicate that the ATX level must be carefully regulated to ensure coordinated vascular formation.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yukiura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Kuniyuki
authors.initials: K
authors.lastname: Kano
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kise
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan; PREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan; CREST, Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000002:abnormalities*; D005260:Female; D005804:Genes, Lethal; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D000099189:Lysophospholipase D
chemical_list: D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D