BP-3, a novel member of the CD38/ADP-ribosyl cyclase family: Its function and regulation in immune system development.

摘要

Murine BP-3 cell surface antigen is a variably glycosylated glycosyl-phosphatidylinositol-linked molecule that is expressed by early B and T lineage cells, myeloid cells, and discrete reticular cells in the peripheral lymphoid organs. It is also expressed on the brush border of intestinal epithelial cells and the lumenal surface of renal collecting tubules, suggesting that it may be an ectoenzyme. As a first step toward understanding the physiological role(s) of the BP-3 molecule, the BP-3 cDNA was cloned, sequenced, and expressed. Two BP-3 gene transcripts were found to share the same open reading frame, but to utilize different polyadenylation sites.;To study the regulatory mechanism of the BP-3 gene expression, the transcription start sites of the BP-3 gene were determined in a pro-B cell line. The major transcriptional start site (;To understand BP-3 function in the immune system development, a BP-3 knockout vector was constructed and used for gene targeting in embryonic stem cells. These cells have been implanted into blastocytes to create a BP-3 gene-deficient mouse model.;A search for BP-3-related gene sequences in available databases indicated that BP-3 is a novel gene that shares significant homology with CD38 and molluscan ADP-ribosyl cyclase, enzymes that generate the calcium mobilizing agent cyclic ADP-ribose from NAD. The recombinant BP-3 molecule has relatively low ADP-ribosyl cyclase enzyme activity, measurable only at pH 4.0. The BP3 gene was mapped to mouse chromosome 5, very near the gene for CD38, supporting the view that they arose by gene duplication. Analysis of genomic clones indicates that the BP-3 gene consists of 9 exons and spans approximately 27 kb. The overall exon organization of the BP-3 gene is very similar to that reported for the ADP-ribosyl cyclase gene in the mollusc, Aphysia kurodai.