Organization, structure, and function of 95 kb of DNA spanning the murine T-cell receptor [formula omitted] region

Abstract

We have analyzed the organization, structure, and function of the murine T-cell receptor Cα Cδ region. This region spans 94.6 kb of DNA and contains the Cα and Cδ genes, as well as the Vδ5, Jδ2, and 50 different Jα gene segments. Within this sequence we have identified 15 new Jα gene segments, 40 new 5′ RNA splice signals, and 40 new DNA rearrangement signals for the Jα gene segments. The murine Cα Cδ sequence contains an exceptionally high level of coding sequence with over 5.7% of the total sequence found in the exons. This is much more than that found in the β-globin locus and the HPRT locus. Using the sequence data obtained from the Cα Cδ region, we have designed simple assays to test for Jα gene segment transcription and to determine the level of polymorphism for simple repeat sequences among different inbred strains of mice using the polymerase chain reaction. Furthermore, comparisons of this 95 kb of sequence with the available sequence from homologous regions of other species have led to the identification of a highly conserved sequence that is present throughout vertebrates and in the mouse binds lymphocyte-specific nuclear proteins. Comparisons of a 10-kb region, which includes the Cα gene in human and mouse, average 66% sequence similarity. These studies support the contention that large-scale DNA sequencing projects of homologous regions of mouse and human will provide powerful new tools for studying the biology and evolution of loci such as the T-cell receptor and for identifying and posing new questions about the functions of conserved sequences.