Cellular and Molecular Biological Studies of a Retroviral Induced Lymphoma, Transmitted via Breast Milk in a Mouse Model
The objective of this study is to determine the phenotype of lymphoma associated with temperature sensitive Moloney Murine Leukemia Virus (Mo-MuLV-ts1) retrovirus and the alteration in specific genes of mRNA expression in these lymphomas. MoMuLV-ts1 infection in BALB/c mice mimics HIV infection in humans. In previous work, we have demonstrated breast milk transmitted Mo-MuLV-ts1 infection and subsequent lymphoma development in offspring. In this experiment, a total of 146 pups from BALB/c mice were divided into 5 groups; one control and 4 experimental. Splenic tissues were used for immunohisto-chemistry, Inverse-PCR and quantitative real-time PCR (RT-PCR). Through studying viral integration sites, twenty-seven genes were identified as candidate genes in lymphoma development. mRNA expression levels for each of 27 genes were determined using a standard curve method, normalized for GAPDH gene expression. A total of 13 pups developed lymphoma of which 7 suckled either from their infected biological or surrogate mothers and developed T-cell lymphoma (Group #1 and #2). Six pups from control mother that suckled from infected surrogate mother (Group #3) developed T-cell lymphoma and B-cell lymphoma. The cells of these lymphomas expressed significantly higher levels of mRNA for two genes (Gfi1 and Ncor2). Two other genes (Ahi1 and Tacc3) were found to be generally significantly upregulated in all lymphomas. Our results indicated that ts1 integration activates the expression of four cellular genes including Ahi1, Ncor2, Tacc3, and Gfi1 that may contribute to lymphomagenesis.
School:University of Toledo Health Science Campus
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:retro viruses hiv lymphomas mo mulv ts1 mother to child transmission breast milk
Date of Publication:01/01/2008