Doctoral Dissertations

Date of Award

8-1989

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biomedical Sciences

Major Professor

Raymond A. Popp

Committee Members

Howard A. Adler, Frank W. Larimer, Richard J. Mural, Juliam Preston, Bob Ulrich

Abstract

Mus musculus strains C57BL/10 and C57BL/10.F are congenic. Both strains carry a germline murine leukemia provirus, emv-2<.u>, on chromosome 8 but differ in the expression of ecotropic MuLV. Southern analysis of restriction endonuclease digested DNA and hybridization with a 400 base pair ecotropic virus specific probe were used to detect ecotropic proviruses. Restriction fragment length polymorphisms were used to identify unique proviral sequences, to determine partial restriction maps, and to examine the frequency and location of proviral integration of ecotropic MuLVs in the somatic cell DNA of these strains of mice.

DNA from the spleens of six-month-old male BIO.F mice contained multiple copies of ecotropic proviruses that were not detected in the BIO mice. Every BIO.F mouse examined contained a provirus different from emv- 2; this provirus was designated BlOFv. In addition to emv-2 and BlOFv, a variety of other novel proviruses were found in the DNA of BIO.F splenocytes. These proviruses were integrated into many different sites in the DNA at an average freguency of two copies per cell. These novel proviruses may be recombinant viruses generated in these highly viremic animals. DNA from spleens and lymph nodes contained more copies of these proviruses than did DNA from nonlymphatic tissues (e.g. liver and kidney).

To study the effects of radiation on the integration and appearance of novel acquired proviruses in the C57BL/10.F mice, two-month-old male mice were exposed to a single dose of 1, 2, or 3 Gy of X-rays. Four months after the 2 and 3 Gy exposure there was an increase in the number of mice with enlarged spleens, incidence and severity of histopathological changes in the spleens, clonal expansion of cells containing a common provirus, and the number of spleens containing novel acquired proviruses.

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