Germ line insertions of moloney murine leukemia virus in the TLL mouse causes site-specific differences in lymphoma/leukemia frequency and tumor immunophenotype.
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.


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.


CONCLUSIONS
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.
Johansson
Ann-Sofie
AS
Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, S-90185 Umeå, Sweden.
Eriksson
Maria
M
Norén-Nyström
Ulrika
U
Larefalk
Asa
A
Eriksson
Björn
B
Holmberg
Dan
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016130:Immunophenotyping; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000235:genetics*; D016662:Virus Integration