There are four aspects of Tla gene regulation, reflecting: 1) Cell lineage and developmental stage; TL is expressed constitutively only by thymocytes. 2) Genomic variation; Tlab mice do not express TL. 3) Differentiation; prothymocytes express TL after hormonal induction. 4) Aberrant expression; some leukemias of Tlab mice express TL. In the Gix system, unlike TL, the product at the cell surface (Gix-gp70) represents a normally non- productive integrated retrovirus genome obeying mendelian rules and expression may be regulated by an unlinked gene. Expression of Gix and productive infection may accompany leukemic transformation in Gix- mice. The existence of Gix- mice, and the occurrence of Gix+ leukemias in Gix- mice, are parallels with Tla. These two systems offer instructive models of the aberrant regulation of cellular genes (Tla), and integrated retroviral genomic genes (Env Gix-gp70), by leukemic cells. It is proposed to clone and structurally compare Tlaa (expressor), Tlab (non- expressor) and Tlac (low-expressor) genes to identify any differences in promotor, enhancer or other gene constituents which may account for differential regulation in the four situations noted. Exon shuffling should be helpful particularly in eludicating the basis of physiological TL expression according to cell lineage and differentiational sequence. A further aim is to analyse a suggestion, revealed in Preliminary Studies, of regional homology between Tla and what may be a linked Q gene expressed in different hematopoietic lineages. Other opportunities are provided by the Gix system, representing the gp70 product of the Env gene of integrated retrovirus, expressed in mendelian fashion in the non-productive viral mode. The intention is to clone structural Gix cDNA and genomic DNA, making use of viral gp70 Env as a probe, and Gix antiserum and monoclonal antibody to recognize the product. Cloning of a regulatory gene can then be undertaken by monitoring Gix expression serologically on thymocytes, the prime Gix-expressor cell type, of radiation chimeras restored with bone marrow cells transfected with the candidate gene by means of the pZIP-NeoSV(X) vector system. Isolation and comparison of Gix genes of Gix non-expressor normal cells and Gix-expressor leukemia cells of identical origin is intended to trace a genomic basis for aberrant Gix expression accompanying leukemic transformation, and any relation that may have to aberrant Tla expression.
| Horie, M; Matsuura, A; Chang, K J et al. (1991) Properties of the promoter region of the T18d (T13c) Tla gene. Immunogenetics 33:171-7 |
| Horie, M; Niikawa, J; Chang, K J et al. (1991) A role for the interferon response DNA sequence in directing transcription of the T18d Tla gene. Immunogenetics 34:293-8 |
| Matsuura, A; Schloss, R; Shen, F W et al. (1989) Expression of the Q8/9d gene by T cells of the mouse. Immunogenetics 30:156-61 |
