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RT6 is a developmentally regulated cell-surface membrane adenosine 5′-diphosphate-ribosyltransferase/nicotinamide adenine dinucleotide-glycohydrolase inserted within the membrane by a glycophosphatidylinositol anchor. In the rat it is restricted to mature T lymphocytes and a subpopulation of natural killer cells. With respect to the data now available, three aspects concerning the function of RT6 are discussed: first, the meaning of the marked polymorphisms; second, its enzymatic activity; third, its possible role concerning T-cell survival. The observation that the rat RT6 gene contains two transcription start sites suggests their different use by distinct subpopulations of T cells. The fact that the expression of RT6 is defective in lymphopenic diabetes prone (DP-BB) rats, although the RT6 gene is structurally not grossly altered in these animals, makes this rat strain a promising model to study the biological meaning of RT6. While it mostly is believed that the RT6 expression defect of the DP-BB rat is a consequence of the lymphopenia, the present paper discusses the possibility that the RT6 expression defect is causally involved in the lymphopenia, and that a normal expression of RT6 may protect the recent thymic emigrants from apoptosis. [ABSTRACT FROM AUTHOR]

With draft copies of several model genomes available in the near future, attention is turning towards the genetic mechanisms that determine differences between individuals. While mutations in protein coding regions affect the structure of gene products, polymorphisms outside such regions may cause quantitative differences in gene expression. Here we summarize observations indicating that such differences may be mediated by allele-specific alterations in the modification or structure of DNA. Mono-allelic expression of the rat T-cell differentiation marker RT6 in a subpopulation of cells is associated with allele-specific differences in DNA methylation in the RT6 promoter. In contrast to previously described examples of mono-allelic expression, these are determined neither stochastically nor by parental origin, but by cis-acting elements within the alleles. An attractive candidate is a rodent identifier (ID) element exclusively present in the RT6α allele. In the case of the rat nucleolin gene, a polymorphic dinucleotide repeat in the 5′ region modulates promoter strength and form left-handed Z-DNA in vivo. Models explaining putative effects of DNA formation on transcription are presented. These observations suggest novel mechanisms by which repetitive DNA, an abundant source of polymorphism in the mammalian genome, may exert quantitative effects on gene expression. [ABSTRACT FROM AUTHOR]