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Leukemic predisposition of pSca-1/Cb2 transgenic mice
Marieke Joosten1, Peter J M Valk, Meritxell Alberich Jordà
1The Institute of Hematology, Erasmus University Rotterdam, Rotterdam, The Netherlands.
Experimental Hematology
|February 2, 2002
Summary
Overexpression of the peripheral cannabinoid receptor Cb2 (also known as Cb2) in mice did not cause hematopoietic defects but increased leukemia susceptibility. Cb2 and Evi1 may collaborate in leukemogenesis.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- The peripheral cannabinoid receptor Cb2 (Cb2) gene is located at the Evi11 locus, a common viral integration site linked to hematopoietic malignancies in mice.
- Understanding the role of Cb2 in hematopoietic development and its potential involvement in cancer is crucial.
Purpose of the Study:
- To investigate the in vivo effects of Cb2 overexpression on hematopoietic development.
- To determine if Cb2 influences susceptibility to leukemia.
Main Methods:
- Generated Cb2 transgenic mice using a Sca-1 promoter to control Cb2 expression.
- Assessed hematopoietic development and Cb2 expression levels via RNase protection and ligand binding assays.
- Investigated leukemic predisposition by infecting transgenic and control mice with Cas-Br-M murine leukemia virus.
Main Results:
- Increased Cb2 gene expression in hematopoietic tissues did not result in observable hematologic defects over a year.
- pSca-1/Cb2 transgenic mice infected with Cas-Br-M MuLV showed a significantly higher incidence of leukemia compared to controls.
- Evidence suggests Evi1 may be overexpressed in virus-induced leukemias in these transgenic mice.
Conclusions:
- Hematopoietic precursor cells with high Cb2 levels exhibit increased susceptibility to leukemia development.
- Cb2 and Evi1 show potential collaborative roles in the process of leukemogenesis.