Date of Award
Doctor of Philosophy
Analysis of DNA from retrovirally induced tumours has revealed that the host sequences disrupted by retroviral integration in multiple independent tumours are "tagged" as genes critical to normal cell proliferation and differentiation. During retroviral infection, retroviral integration occurs randomly into many sites in the host genome. However retrovirally induced tumours can be shown to have originated from a single cell which has sustained genetic damage to particular cell sequences. Damage to these cell sequences has contributed to the development of this clone of cells into a tumour. Genes identified in this way are invaluable to the understanding of neoplastic as well as normal cell growth because they point to cellular functions which can not be otherwise assayed.;In order to investigate the molecular mechanisms by which a murine retrovirus, TBLV, induces thymic lymphoma, DNA from multiple independent tumours was analysed for the existence of a cellular region frequently disrupted by the presence of a provirus. Such a common locus of integration was found. The uninterrupted, normal equivalent region of mouse cellular DNA was isolated from a genomic library and analysed for its potential to encode a functional gene.;DNA sequences from the common locus of integration which has been named Tblvi-1 were found to be conserved amongst diverse eukaryotic species and expressed in mRNA from normal mouse tissues and tumour tissues which suggest it represents a functional cellular gene. The locus was mapped to the mouse X chromosome and represents a novel genetic locus involved in tumour development.
Mueller, Rosemary Ellen, "Identification And Analysis Of A Genetic Locus, Tblvi-1, Frequently Disrupted By Retroviral Integration In Murine Thymic Lymphomas" (1992). Digitized Theses. 2145.