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Humanbcr-abl gene has a lethal effect on embryogenesis
Authors:Nora Heisterkamp  Guido Jenster  Dimitris Kioussis  Paul K Pattengale  John Groffen
Institution:(1) Section of Molecular Diagnosis, Department of Pathology, Childrens Hospital of Los Angeles, 4650 Sunset Boulevard, 90027 Los Angeles, CA, USA;(2) Section of Hematopathology, Department of Pathology, Childrens Hospital of Los Angeles, 4650 Sunset Boulevard, 90027 Los Angeles, CA, USA;(3) Laboratory of Gene Structure and Expression, National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA London, UK
Abstract:The chimaericbcr-abl oncogene is thought to have a crucial role in the development or maintenance of chronic nyelogenous leukaemia. To study this oncogene in a more direct way, thebcr-abl gene encoding the P210 protein under control of thebcr gene promoter was introduced into fertilized one-cell embryos, which were then re-implanted into foster mothers. Our data, obtained after several experiments, demonstrate that no live transgenic progeny could be obtained using thisbcr-abl construct. Thebcr gene is expressed in the course of embryogenesis and thebcr-abl gene product appears to have a pleiotropic lethal effect during this period of development. In concordance, several gross abnormalities were observed while no evidence of neoplastic formation was found. These results suggest that thebcr-abl encoded protein severely affects the process of normal embryogenesis.
Keywords:bcr-abl  lethality  embryogenesis  oncogene
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