An intracisternal A-particle DNA sequence is closely linked to the thrombomodulin gene in some strains of laboratory mice

Abstract

Sequence analysis of the 5' end of the thrombomodulin (TM) gene has identified a difference in two strains of laboratory mice, BALB/cBD (maintained at the Oak Ridge National Laboratory) and the strain used for the sequence listed in the GenBank data base. An intracisternal A-particle (IAP) provirus was present in the BALB/cBD sequence but absent from the GenBank sequence. Thus, there are two different 5' regions for the TM gene in mice. Southern blot and polymerase chain reaction analyses on other mouse strains demonstrated the presence of this proviral sequence in five out of ten strains tested. Northern blot analyses demonstrated that there were differences (up to three-fold) in the steady-state levels of TM mRNA among the strains. However, TM mRNA levels did not correlate directly with the presence of the IAP DNA upstream from the TM gene. This is in contrast to other loci (the interleukin-3 gene, c-mos, and the immunoglobulin Ck gene), in which the IAP element is known to affect levels of RNA transcription. While the IAP provirus does not appear to have an effect on TM transcription under normal conditions, it is possible that transcription levels altered by factors like thrombin and tumor necrosis factor are affected by the IAP provirus.