Coding joint formation of endogenous T cell receptor genes in lymphoid cells from scid mice: unusual P-nucleotide additions in VJ-coding joints.

The mouse mutation scid adversely affects the process of VDJ recombination. Attempts to form coding joints, that is, to joint V or D to J gene segments generally fail in developing scid lymphocytes. It has been proposed that the scid mutation results a defective VDJ recombinase system. Here we describe five scid T cell lymphomas containing one or two TcR gamma coding joints each, even though the majority of the multiple TcR gamma chain gene rearrangements and all TcR beta rearrangements in these cells were abnormal with the deletions typically found in scid lymphoid cells. One of the five T cell lymphomas was shown to have an active VDJ recombinase system; however, this activity was defective indicating that the scid phenotype has been retained. We conclude that the scid VDJ recombinase system has not completely lost the ability to form coding joints. P-nucleotide additions of unusual length or composition were found at the junctional border in five of the eight TcR gamma coding joints. This might reflect a defect in the activity of a component of the VDJ recombinase system involved in the generation of P-nucleotide additions. In one of the observed rearrangements, a V gamma 5-J gamma 3 coding joint was formed. This establishes the transcriptional orientation of J gamma 3-C gamma 3 and confirms a previously proposed organization of the TcR gamma genes.