We previously identified KEPI as a morphine-regulated gene using subtractive hybridization and differential display PCR. Upon phosphorylation by protein kinase C, KEPI becomes a powerful inhibitor of protein phosphatase 1. To gain insights into KEPI functions, we created KEPI knockout (KO) mice on mixed 129S6 × C57BL/6 genetic backgrounds. KEPI maps onto mouse chromosome 10 close to the locus that contains the μ-opioid receptor (Oprm1) and provides a major quantitative trait locus for morphine effects. Analysis of single nucleotide polymorphisms in and near the Oprm1 locus identified a doubly-recombinant mouse with C57BL/6 markers within 1 Mb on either side of the KEPI deletion. This strategy minimized the amount of 129S6 DNA surrounding the transgene and documented the C57BL/6 origin of the Oprm1 gene in this founder and its offspring. Recombinant KEPIKO mice displayed a) normal analgesic responses and normal locomotion after initial morphine treatments, b) accelerated development of tolerance to analgesic effects of morphine, c) elevated activity of protein phosphatase 1 in thalamus, d) attenuated morphine reward as assessed by conditioned place preference. These data support roles for KEPI action in adaptive responses to repeated administration of morphine that include analgesic tolerance and drug reward.

A human cholecystokinin-B/gastrin receptor cDNA (CCKBR) has been recently cloned and its transcriptional product has been characterized. The cDNA probe was mapped by fluorescence in situ hybridization to chromosome 11 at bands p15.5→p15.4. The localization of this receptor gene provides a useful marker for this region of chromosome 11 permitting the identification of diseases involving the gene and interactions with other genes.

In this study, CA46 and ST486, two Epstein-Barr (EBV) negative cell lines derived from sporadic BL, were analyzed by multicolor spectral karyotyping, G-banding, fluorescence in situ hybridization with single-copy gene probes, and comparative genomic hybridization (CGH). In addition to reciprocal t(8;14)(q24;q32) translocation involving c-myc and IgH loci, we identified a t(7;8;14)(q11.2;q24;q32) translocation in CA 46 cells and t(8;14;18)(q24;q32;q23) in ST486 cells. Both rearrangements were not previously described in BL and resulted in transposition of myc sequences in a new genomic configuration. Several DNA imbalances mapped by CGH at the same sites in both lines, may reflect recurrent genomic changes that are relevant to pathogenesis of BL. We tested the tumorigeni-

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