International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 112 - GENETIC INSTABILITY IN A TRANSGENIC MOUSE MODEL FOR PHILADELPHIACHROMOSOME-POSITIVE ALL

Rudolph C
Institute of Cell and Molecular Pathology, Hannover Medical School

Co-Authors: 1) Steinemann D, 2) Hegazy AN, 3) Schrock E, 2) Klein C, 1) Schlegelberger B
Institutions: 1) Institute of Cell and Molecular Pathology, Hannover Medical School, 2) Department of Pediatric Hematology and Oncology, Hannover Medical School, 3) Institute of Clinical Genetics, Dresden

Aims: Retrovirally induced expression of fusion proteins in human and mouse cells is a common tool to understand the development and progression of hematologic malignancies. Recently, chromosome aberrations, syntenic with those in human leukemias, were found in a double transgenic mouse model for AML M3. We therefore investigated a possible genetic instability and karyotypic evolution after transfection of BM185wt cells using Spectral Karyotyping (SKY) and fluorescence in situ hybridization (FISH). This mouse pre-B-cell line is characterized by the retrovirally induced expression of the p185 BCR-ABL fusion protein and represents an in vitro model for Philadelphia-chromosome-positive acute lymphocytic leukemia (ALL). Methods: Chromosome preparations were made from BM185wt cells and from BM185wt cells retrovirally transfected to express ovalbumin-GFP or GFP alone, to study T-cell response. Hybridization with the SKY probe was performed according to manufacturer`s instructions (Applied Spectral Imaging). To determine the quantity of cells with Der(12)T(XE?;12D), a FISH probe was generated from BAC clone RP23-382J5, hybridizing to region F2 of the X-chromosome. Results: SKY analysis revealed numerical and structural chromosomal alterations in all cell lines. In the mostly hyperdiploid chromosome complements we detected additional chromosomes 5, 12, 18 and loss of the Y-chromosome. An unbalanced translocation, involving parts of chromosomes X and 12, was found in 15% of BM185wt cells and 12% of ovalbumin-GFP-expressing cells by FISH analysis. Conclusions: The chromosomal instability observed in this transgenic mouse model for Philadelphia-chromosome-positive ALL might be induced by BCR-ABL expression. Our findings may help to find chromosomal regions involved in leukemogenesis and tumor progression.


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