Human bcr-abl gene has a lethal effect on embryogenesis.
The chimaeric bcr-abl oncogene is thought to have a crucial role in the development or maintenance of chronic myelogenous leukaemia. To study this oncogene in a more direct way, the bcr-abl gene encoding the P210 protein under control of the bcr 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 this bcr-abl construct. The bcr gene is expressed in the course of embryogenesis and the bcr-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 the bcr-abl encoded protein severely affects the process of normal embryogenesis.
Heisterkamp
N
N
Section of Molecular Diagnosis, Childrens Hospital of Los Angeles, CA 90027.
Jenster
G
G
Kioussis
D
D
Pattengale
P K
PK
Groffen
J
J
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D004622:Embryo, Mammalian / Q000502:physiology*; D005313:Fetal Death; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005804:Genes, Lethal; D016313:Genes, abl; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009857:Oncogenes; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping
D009838:Oligodeoxyribonucleotides; D012313:RNA; D016044:Fusion Proteins, bcr-abl