GAMMA-GLUTAMYL LEUKOTRIENASE, A GAMMA-GLUTAMYL-TRANSPEPTIDASE GENE FAMILY MEMBER, IS EXPRESSED PRIMARILY IN SPLEEN

We have recently identified a mouse enzyme termed gamma-glutamyl leuko trienase (GGL) that converts leukotriene C-4 (LTC4) to leukotriene D-4 (LTD4). It also cleaves some other glutathione (GSH) conjugates, but not GSH itself (Carter, B. Z., Wiseman, A. L., Orkiszewski, R., Ballar d, K. D., Ou, C.-N., and Lieberman, M.W. (1997) J. Biol. Chem. 272, 12 305-12310). We have now cloned a full-length mouse cDNA coding for GGL activity and the corresponding gene. GGL and gamma-glutamyl transpept idase constitute a small gene family. The two cDNAs share a 57% nucleo tide identity and 41% predicted amino acid sequence identity. Their co rresponding genes have a similar intron-exon organization and are loca ted 3 kilobases apart. A search of Genbank and reverse transcription-p olymerase chain reaction analysis failed to identify additional family members. Mapping of the GGL transcription start site revealed that th e GGL promoter is TATA-less but contains an initiator, a control eleme nt for transcription initiation. Northern blots for GGL expression wer e negative. As judged by ribonuclease protection, in situ hybridizatio n, and measurement of enzyme activity, spleen had the highest level of GGL expression. GGL is also expressed in thymic lymphocytes, bronchio lar epithelial cells, pulmonary interstitial cells, renal proximal con voluted tubular cells, and crypt cells of the small intestine as well as in cerebral. cerebellar, and brain stem neurons but not in glial ce lls. GGL is widely distributed in mice, suggesting an important role f or this enzyme.