title: Ornithine-δ-Aminotransferase Inhibits Neurogenesis During Xenopus Embryonic Development.
abstract: OBJECTIVE
  In humans, deficiency of ornithine-δ-aminotransferase (OAT) results in progressive degeneration of the neural retina (gyrate atrophy) with blindness in the fourth decade. In this study, we used the Xenopus embryonic developmental model to study functions of the OAT gene on embryonic development.
  
  
  METHODS
  We cloned and sequenced full-length OAT cDNA from Xenopus oocytes (X-OAT) and determined X-OAT expression in various developmental stages of Xenopus embryos and in a variety of adult tissues. The phenotype, gene expression of neural developmental markers, and enzymatic activity were detected by gain-of-function and loss-of-function manipulations.
  
  
  RESULTS
  We showed that X-OAT is essential for Xenopus embryonic development, and overexpression of X-OAT produces a ventralized phenotype characterized by a small head, lack of axial structure, and defective expression of neural developmental markers. Using X-OAT mutants based on mutations identified in humans, we found that substitution of both Arg 180 and Leu 402 abrogated both X-OAT enzymatic activity and ability to modulate the developmental phenotype. Neurogenesis is inhibited by X-OAT during Xenopus embryonic development.
  
  
  CONCLUSIONS
  Neurogenesis is inhibited by X-OAT during Xenopus embryonic development, but it is essential for Xenopus embryonic development. The Arg 180 and Leu 402 are crucial for these effects of the OAT molecule in development.
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Basic Research Program, Leidos, Inc., National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, United States.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Cooper
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, United States.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Mei
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Basic Research Program, Leidos, Inc., National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, United States.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Borchert
authors.affiliation: Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, United States.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Donald
authors.affiliation: State Key Laboratory of Oncology in Southern China, and Centre for Emerging Infectious Diseases, the Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.affiliation: Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Phang
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055495:Neurogenesis / Q000235:genetics*; D009953:Ornithine-Oxo-Acid Transaminase / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: D012313:RNA; D009953:Ornithine-Oxo-Acid Transaminase