Increase in mutant frequencies in mice expressing the BCR-ABL activated tyrosine kinase.
The acquisition of the Philadelphia (Ph) chromosome (or BCR-ABL translocation) represents a detrimental pathophysiological event in humans. The activated tyrosine kinases, which are produced by this translocation, are associated with fatal hematological malignancies. The initial molecular dissection of BCR-ABL has linked the expression of this constitutively activated kinase with enhanced genomic instability. We directly evaluated the consequence of BCR-ABL expression on genomic instability using the Big Blue in vivo mutagenesis mouse system. We report that the expression of BCR-ABL in both spleens and kidneys confers a mutator phenotype represented by a statistically significant elevation in mutant frequencies.
Salloukh
H F
HF
Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada.
Laneuville
P
P
D000818:Animals; D004789:Enzyme Activation; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl