EXPRESSION IN BALB C AND C57BL/6 MICE OF RT6-1 AND RT6-2 ADP-RIBOSYLTRANSFERASES THAT DIFFER IN ENZYMATIC-ACTIVITY - C57BL/6 RT6-1 IS A NATURAL TRANSFERASE KNOCKOUT/

Several proteins with NAD(+) :arginine ADP-ribosyltransferase (ART) ac tivity are expressed in T cells and affect their function. Rat T cells that express the ART designated RT6 are determinants of the expressio n of autoimmune diabetes. In the mouse, a 35-kDa ecto-ART modulates th e proliferation and functional activity of CTL. Here we report on mous e ARTs designated Rt6-1 and Rt6-2 in BALB/c and C57BL/6 mice. mRNAs fo r Rt6-1 and Rt6-2 were found in spleen, thymus, and intestinal tissue of both strains, but Rt6-1 mRNA in C57BL/6 mice was detected only at l ow levels, Rt6-1 and Rt6-2 cDNAs from both strains were cloned and seq uenced. Predicted amino acid sequences of Rt6-2 were identical in both strains, but there was an in-frame stop codon in the sequence of Rt6- 1 in C57BL/6 mice not present in BALB/c mice, Recombinant C57BL/6 Rt6- 2 and BALB/c Rt6-1 proteins expressed in COS1 cells exhibited ART acti vity and were documented to be glycosylphosphatidylinositol-linked mem brane proteins, COS-1 cells transfected with a C57BL/6 Rt6-1 cDNA cons truct expressed a truncated protein consistent in size with that predi cted by the presence of the stop codon. This similar to 21-kDa protein appeared not to be glycosylphosphatidylinositol linked to the cell su rface and lacked ART activity, C57BL/6 Rt6-1 therefore appears to be a naturally occurring ART knockout. The expression of Rt6-1 and Rt6-2 m RNAs in lymphoid tissues suggests that these ARTs may regulate immune system functions. Expression of Rt6-2 or another redundant ART may com pensate for the lack of enzymatically active Rt6-1 in C57BL/6 mice.