論文 - 詳細
| RRC ID | 2495 |
|---|---|
| 著者 | Hanaoka R, Katayama S, Dawid IB, Kawahara A. |
| タイトル | Characterization of the heme synthesis enzyme coproporphyrinogen oxidase (CPO) in zebrafish erythrogenesis. |
| ジャーナル | Genes Cells |
| Abstract |
Hemoglobin consists of heme and globin proteins and is essential for oxygen transport in all vertebrates. Although biochemical features of heme synthesis enzymes have been well characterized, the function of these enzymes in early embryogenesis is not fully understood. We found that the sixth heme synthesis enzyme, coproporphyrinogen oxidase (CPO), is predominantly expressed in the intermediate cell mass (ICM) that is a major site of zebrafish primitive hematopoiesis. Knockdown of zebrafish CPO using anti-sense morpholinos (CPO-MO) leads to a significant suppression of hemoglobin production without apparent reduction of blood cells. Injection of human CPO RNA, but not a mutant CPO RNA that is similar to a mutant responsible for a hereditary coproporphyria (HCP), restores hemoglobin production in the CPO-MO-injected embryos. Furthermore, expression of CPO in the ICM is severely suppressed in both vlad tepes/gata1 mutants and in biklf-MO-injected embryos. In contrast, over-expression of biklf and gata1 significantly induces ectopic CPO expression. The function of CPO in heme biosynthesis is apparently conserved between zebrafish and human, suggesting that CPO-MO-injected zebrafish embryos might be a useful in vivo assay system to measure the biological activity of human CPO mutations. |
| 巻・号 | 11(3) |
| ページ | 293-303 |
| 公開日 | 2006-3-1 |
| DOI | 10.1111/j.1365-2443.2006.00939.x |
| PII | GTC939 |
| PMID | 16483317 |
| MeSH | Amino Acid Sequence Animals Blood Cells / metabolism Coproporphyrinogen Oxidase / antagonists & inhibitors Coproporphyrinogen Oxidase / metabolism* Embryo, Mammalian / cytology Embryo, Mammalian / drug effects Embryo, Mammalian / metabolism Embryo, Nonmammalian Erythropoiesis* GATA1 Transcription Factor / chemistry GATA1 Transcription Factor / genetics GATA1 Transcription Factor / metabolism Gene Expression Regulation, Developmental* Hematopoiesis Hemoglobins / metabolism Humans In Situ Hybridization Kruppel-Like Transcription Factors / chemistry Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism Microinjections Molecular Sequence Data Oligonucleotides, Antisense / genetics Oligonucleotides, Antisense / pharmacology Sequence Homology, Amino Acid Zebrafish / embryology Zebrafish / genetics Zebrafish / metabolism* Zebrafish Proteins / chemistry Zebrafish Proteins / genetics Zebrafish Proteins / metabolism |
| IF | 1.655 |
| 引用数 | 16 |
| WOS 分野 | GENETICS & HEREDITY CELL BIOLOGY |
| リソース情報 | |
| ゼブラフィッシュ | RIKEN WT (RW) |