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Chunk #22 — Introduction — Mouse models of CLL — TCL1 driven CLL mouse model

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Molecular basis of CLL.
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Several years ago, we produced transgenic mice in which the expression of TCL1 was under the control of a VH promoter-IgH-Eμ enhancer that targets expression of the transgene to immature and mature B-cells [31]. The immuno-phenotypic profile of peripheral blood lymphocytes (PBLs) from these mice between one and nine months of age detected an expansion of the B220/IgM+ population, in particular those that were CD5+/B1, whereas such cells are generally infrequent [48]. This expansion was revealed in 100% of the transgenic mice by six months of age, without sign of clinical disease [31]. Fluorescence-activated cell sorting (FACS) analysis detected a phenotypically homogeneous CD5+IgM+ population significantly expanded in the peritoneal cavity of the transgenic mice starting at two months of age (44%) that became then evident in spleen (9%) by four months and bone marrow by eight months (43%) [21, 31]. At this age, Eμ-TCL1 mice presented a slightly enlarged spleen and a much higher cellularity in the peritoneal cavity, ranging between 50- to 100-fold increase. The cell cycle distribution and the rate of cell proliferation in spleen and peritoneal cavity