TitleThe α-tocopherol transfer protein is essential for vertebrate embryogenesis.
Publication TypeJournal Article
Year of Publication2012
AuthorsMiller, GW, Ulatowski, L, Labut, EM, Lebold, KM, Manor, D, Atkinson, J, Barton, CL, Tanguay, RL, Traber, MG
JournalPLoS One
Volume7
Issue10
Paginatione47402
Date Published2012
ISSN1932-6203
Keywordsalpha-Tocopherol, Animals, Carrier Proteins, Central Nervous System, Embryonic Development, Gene Expression Regulation, Developmental, Humans, Vertebrates, Vitamin E, Vitamin E Deficiency, Zebrafish
Abstract

The hepatic α-tocopherol transfer protein (TTP) is required for optimal α-tocopherol bioavailability in humans; mutations in the human TTPA gene result in the heritable disorder ataxia with vitamin E deficiency (AVED, OMIM #277460). TTP is also expressed in mammalian uterine and placental cells and in the human embryonic yolk-sac, underscoring TTP's significance during fetal development. TTP and vitamin E are essential for productive pregnancy in rodents, but their precise physiological role in embryogenesis is unknown. We hypothesize that TTP is required to regulate delivery of α-tocopherol to critical target sites in the developing embryo. We tested to find if TTP is essential for proper vertebrate development, utilizing the zebrafish as a non-placental model. We verify that TTP is expressed in the adult zebrafish and its amino acid sequence is homologous to the human ortholog. We show that embryonic transcription of TTP mRNA increases >7-fold during the first 24 hours following fertilization. In situ hybridization demonstrates that Ttpa transcripts are localized in the developing brain, eyes and tail bud at 1-day post fertilization. Inhibiting TTP expression using oligonucleotide morpholinos results in severe malformations of the head and eyes in nearly all morpholino-injected embryos (88% compared with 5.6% in those injected with control morpholinos or 1.7% in non-injected embryos). We conclude that TTP is essential for early development of the vertebrate central nervous system.

DOI10.1371/journal.pone.0047402
Alternate JournalPLoS ONE
PubMed ID23077608
PubMed Central IDPMC3471827
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
R01 HD062109 / HD / NICHD NIH HHS / United States
HD062109 / HD / NICHD NIH HHS / United States