one year old Mdr−/− mice showed higher percentages of CD5+B220 B cells among mononuclear cells in the peritoneal cavity (50% vs. 15% in controls). Similar observations were made in miR-15a/16-1−/− rodents. Thus, deletions of the Mdr and miR-15a/16-1 are associated with expansion of CD5+B220 cells in the peritoneal cavity. In a fraction of the animals, clonal CD5+ B cell populations were accompanied by significant infiltration of lymphoid organs with histopathologic features resembling human CLL [56, 57]. These mice displayed an enlargement of the spleen white pulp due to the expansion or accumulation of small lymphocytes with a pattern similar to CLL. Discrete aggregates of small lymphocytes were also observed in the bone marrow. Overall, 27% of Mdr−/− and 21% of miR-15a/16-1−/− mice developed CLL. Altogether 42% of Mdr−/− and 26% of miR-15a/16-1−/− mice, 15–18 months of age, developed some type of clonal B cell lymphoproliferation. Mdr−/− mice also showed a trend toward developing B cell tumors (24%), suggesting that monoallelic deletion of the Mdr can cause disease. This trend is not evident in miR-15a/16-1-deleted mice, probably due to the lower penetrance of the phenotype. Mdr−/− mice died earlier than their wild type littermates, suggesting that the homozygous mice eventually succumb
