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Germ line insertions of moloney murine leukemia virus in the TLL mouse causes site-specific differences in
Ann-Sofie Johansson1, Maria Eriksson, Ulrika Norén-Nyström
1Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, S-90185 Umeå, Sweden.
Background:
Moloney murine leukemia virus (Mo-MLV) has proven valuable for studies of the pathogenesis of malignant lymphoma. Inoculation of newborn mice induces T cell lymphoma with 100% incidence. The TLL (T cell lymphoma/leukemia)-strain was previously established and was shown to spontaneously develop T cell lymphoma at high frequency.
Materials And Methods:
Differential screening of cDNA libraries was performed to discover an involvement of Mo-MLV and genomic sequencing was used to identify the chromosomal position of Mo-ML V proviral integration sites. Immunophenotypes of the tumors were established by flow cytometty. Disease frequency curves were created according to the Kaplan-Meier method.
Results:
Two independent Mo-MLV germ line integrations were characterized on chromosomes 2 and 14, giving rise to two substrains of mice denoted TLL-2 and TLL-14. The chromosomal position of the integrated provirus affected the frequency of disease, as well as the immunophenotype of the tumors.
Conclusion:
The data suggest that factors influencing the transcriptional activity of the chromosomal regions, leading to differences in proviral expression, could underlie the observed difference in tumor frequency.
