Proximity of the CTLA-1 serine esterase and Tcr alpha loci in mouse and man.

Abstract

The serine esterase CTLA-1 gene was shown by in situ hybridization to map to the D segment of mouse chromosome 14, the same localization as a member of the immunoglobulin superfamily, Tcr alpha. To further demonstrate the proximity of CTLA-1 and Tcr alpha, genetic linkage was tested in mouse using restriction fragment length polymorphisms and a backcross progeny, and no recombination was observed in the 100 backcross products studied. Recombination events between Tcr alpha/CTLA-1 and the markers Gdh-X and NP-1 show that the most probable order of these loci in the mouse 14D region is NP-1-Tcr alpha/Ctla-1-Gdh-X. In man, the human homologue of CTLA-1 was shown by in situ hybridization to map on chromosome 14, at 14q11-q12, where Tcr alpha also maps. Using the human cell line SUP-T1, bearing the inversion inv(14) (q11;q32), we further demonstrated the loci order in man to be centromere-NP-1-Tcr alpha-CTLA-1. To complement the cytogenetic and genetic mapping data, we tried to determine the physical distance between the two genes by pulsed field gel electrophoresis (PFGE). DNA prepared from various cell types, both mouse and human, were digested with a panel of rare cutter enzymes and hybridized first with CTLA-1, then with Tcr alpha probes. None of the bands identified hybridized with both Tcr alpha and CTLA-1 probes for either mouse or human cells. Although the physical mapping by PFGE is inconclusive, the cytogenetic and genetic data support close linkage of the Tcr alpha and CTLA-1 genes in both mouse and man, suggesting homology between the D region of mouse chromosome 14 and the q11-q12 region of human chromosome 14, encompassing the Tcr alpha and CTLA-1 loci. These findings also provide another example of proximity of genes coding for a member of the Ig super-family and a serine esterase.