Stumpf Miriam, Choorapoikayil Suma, den Hertog Jeroen
Hubrecht Institute - KNAW and University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
Hubrecht Institute - KNAW and University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands; CNRS, UMR 5235, Dynamique des Interactions Membranaires Normales et Pathologiques, Univ Montpellier 2, 34095 Montpellier, France.
Methods. 2015 May;77-78:191-6. doi: 10.1016/j.ymeth.2014.11.002. Epub 2014 Nov 11.
Zebrafish is an excellent model system for the analysis of gene function. We and others use zebrafish to investigate the function of the tumor suppressor, Pten, in tumorigenesis and embryonic development. Zebrafish have two pten genes, ptena and ptenb. The recently identified N-terminal extension of human PTEN that may facilitate cell membrane transfer, appears not to be conserved in zebrafish Ptena or Ptenb. Mutants that retain a single wild type pten allele develop tumors, predominantly hemangiosarcomas. Homozygous double mutants are embryonic lethal. Zebrafish embryos lacking functional Pten display enhanced proliferation of endothelial cells, resulting in hyperbranching of blood vessels. In addition, ptena-/-ptenb-/- mutant embryos display enhanced proliferation of hematopoietic stem and progenitor cells and concomitant arrest of differentiation, although Pten-deficient cells commit to all blood cell lineages. Zebrafish is an ideal model for intravital imaging and future work using ptena-/-ptenb-/- mutants will enhance our understanding of the function of Pten in vivo.
斑马鱼是用于基因功能分析的优秀模型系统。我们和其他研究人员利用斑马鱼来研究肿瘤抑制因子Pten在肿瘤发生和胚胎发育中的功能。斑马鱼有两个pten基因，ptena和ptenb。最近发现的人类PTEN的N端延伸可能有助于细胞膜转移，但在斑马鱼的Ptena或Ptenb中似乎并不保守。保留单个野生型pten等位基因的突变体发生肿瘤，主要是血管肉瘤。纯合双突变体胚胎致死。缺乏功能性Pten的斑马鱼胚胎显示内皮细胞增殖增强，导致血管过度分支。此外，ptena-/-ptenb-/-突变体胚胎显示造血干细胞和祖细胞增殖增强以及伴随的分化停滞，尽管缺乏Pten的细胞可分化为所有血细胞谱系。斑马鱼是活体成像的理想模型，未来使用ptena-/-ptenb-/-突变体的研究将增进我们对Pten体内功能的理解。
