THE GENES ENCODING THE PERIPHERAL CANNABINOID RECEPTOR AND ALPHA-L-FUCOSIDASE ARE LOCATED NEAR A NEWLY IDENTIFIED COMMON VIRUS INTEGRATION SITE, EVI11

A new common region of virus integration, Evi11, has been identified i n two retrovirally induced murine myeloid leukemia cell lines, NFS107 and NFS78, By interspecific backcross analysis, it was shown that Evi1 1 is located at the distal end of mouse chromosome 4, in a region that shows: homolog with human 1p36, The genes encoding the peripheral can nabinoid receptor (Cnr2) and alpha-L-fucosidase (Fuca1) were identifie d near the integration site by using a novel exon trapping system, Cnr 2 is suggested to be the target gene for viral interference in Evi11, since proviruses are integrated in the first intron of Cnr2 and retrov iral integrations alter mRNA expression of Cnr2 in NFS107 and NFS78, I n addition, proviral integrations were demonstrated within the 3' untr anslated region of Cnr 2 in five independent newly derived CasBrM-MuLV (mouse murine leukemia virus) tumors, CSL13, CSL14 CSL16, CSL27, and CSL97. The Cnr2 gene encodes a seven-transmembrane G-protein-coupled r eceptor which is normally expressed in hematopoietic tissues, Our data suggest that the peripheral cannabinoid receptor gene might he involv ed in leukemogenesis as a result of aberrant expression of Cnr2 due to retroviral integration in Evi11.