title: Impaired Lymphocytes Development and Xenotransplantation of Gastrointestinal Tumor Cells in Prkdc-Null SCID Zebrafish Model.
abstract: Severe combined immunodeficiency (SCID) mice have widely been used as hosts for human tumor cell xenograft study. This animal model, however, is labor intensive. As zebrafish is largely emerging as a promising model system for studying human diseases including cancer, developing efficient immunocompromised strains for tumor xenograft study are also demanded in zebrafish. Here, we have created the Prkdc-null SCID zebrafish model which provides the stable immune-deficient background required for xenotransplantation of tumor cell. In this study, the two transcription activator-like effector nucleases that specifically target the exon3 of the zebrafish Prkdc gene were used to induce a frame shift mutation, causing a complete knockout of the gene function. The SCID zebrafish showed susceptibility to spontaneous infection, a well-known phenotype found in the SCID mutation. Further characterization revealed that the SCID zebrafish contained no functional T and B lymphocytes which reflected the phenotypes identified in the mice SCID model. Intraperitoneal injection of human cancer cells into the adult SCID zebrafish clearly showed tumor cell growth forming into a solid mass. Our present data show the suitability of using the SCID zebrafish strain for xenotransplantation experiments, and in vivo monitoring of the tumor cell growth in the zebrafish demonstrates use of the animal model as a new platform of tumor xenograft study.
authors: Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: In Hye
authors: IH
authors: Jung
authors: Research Institute of SMT Bio, SMT Bio Co., Ltd., Seoul, Republic of Korea.
authors: Yong-Yoon
authors: YY
authors: Chung
authors: Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Dawoon E
authors: DE
authors: Jung
authors: University of Rochester, Hajim School of Engineering and Applied Sciences, USA.
authors: Young Jin
authors: YJ
authors: Kim
authors: Postgraduate School of Nano Science and Technology, Yonsei University, Seoul, Republic of Korea.
authors: Do Hee
authors: do H
authors: Kim
authors: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Kyung-Sik
authors: KS
authors: Kim
authors: Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: swoopark@yuhs.ac.
authors: Seung Woo
authors: SW
authors: Park
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001706:Biopsy; D045744:Cell Line, Tumor; D051747:DNA-Activated Protein Kinase / Q000172:deficiency*; D004195:Disease Models, Animal; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000172:deficiency*; D010641:Phenotype; D014183:Transplantation, Heterologous
chemical_list: D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human