The BCR/ABL oncogene, associated with the t(9;22) Philadelphia chromosome in humans, is characteristic of chronic myeloid leukemia (CML).
These conditional knock-in/knockout mice constitutively express a single copy of the human BCR/ABL p210-IRES-EGFP from the endogenous mouse Bcr locus after the excision of a loxP-flanked Stop cassette. Heterozygous mice are born at predicted Mendlian frequency and display normal growth. Lack of expression of wildtype Bcr results in haploinsufficiency reflected in reduced message and protein.
Progeny derived from a cross with Vav1-cre (e.g. Stock No. 008610) or Mx1-cre (e.g. Stock No. 003556) mice to excise the floxed stop in hematopoietic cells develop the earliest stages of CML, but not leukemia, even when maintained for up to 1.5 years. This contrasts with previous models involving non-Bcr promoters and multiple copies of BCR/ABL. Compound mutant mice have normal white blood cell counts and their differentials display normal myeloid and monocytic frequencies, with only a slight trend of decreased lymphocyte frequencies over the first year of observation. White blood cells and spleen extracts in the compound mutant mice express GFP.
