Gene analysis of signal-joint T cell receptor excision circles and their relationship to age in dogs

Abstract The quantification of DNA excision circles produced during T cell receptor (TCR) rearrangement, termed signal joint TCR rearrangement excision circles (sjTRECs), has been employed as a measure of age and thymic function in humans and animals. δRec-ψJα sjTRECs are ring-shaped DNAs that are generated during TCR δ locus deletion that occurs at a late stage of T cell development. In this study, the nucleotide sequences of δRec-ψJα signal joints of canine δRec-ψJα sjTRECs were analyzed. The gene structure of canine δRec-ψJα signal joints was found to be similar to that of humans and mice. However, diversity of signal joints was detected and found to derive from N nucleotide insertions, recombination signal sequence combinational diversity and single-base substitutions at the recombination signal sequence. In addition, an adenine insertion or deletion was found approximately 280 bases from the ψJα signal end. Blood samples were collected from 46 dogs, ranging in age from 3 to 192 months, with a mean age of 96.4 and a SD of 51.5 months. Although δRec-ψJα sjTRECs were detectable in most of the dogs evaluated, the level did not significantly correlate with age. These results indicated that δRec-ψJα sjTREC levels were ineffective as a measure of age in dogs.