Cloning and functional characterization of the early-lymphocyte-specific Pb99 gene

The Pb99 gene is specifically expressed in pre-B cells and thymocytes and n ot in mature B and T cells or nonlymphoid tissues, implying that it may fun ction in early lymphoid development. We have previously described the cloni ng of an incomplete cDNA for Pb99. Here we report the isolation of full-len gth cDNAs and genomic clones for the murine Pb99 gene and the mapping of it s location to mouse chromosome 8. Sequence analyses of different Pb99 cDNA clones suggest that there may be at least three forms of the Pb99 protein g enerated by differential processing of the Pb99 transcript. The cDNA with t he longest open reading frame encodes a putative protein that has seven hyd rophobic domains similar to those of seven membrane-spanning proteins, such as the classical G protein-coupled receptors. To directly address the role of the Pb99 protein in lymphoid development, Pb99-deficient mice were gene rated by gene targeting, and lymphocyte development in these mice was analy zed.