THE ORGANIZATION AND EXPRESSION OF THE MDM2 GENE

The mdm2 gene encodes a zinc finger protein that negatively regulates p53 function by binding and masking the p53 transcriptional activation domain. Two different promoters control expression of mdm2, one of wh ich is also transactivated by p53. We cloned and characterized the mdm 2 gene from a murine 129 library. It contained at least 12 exons and s panned approximately 25 kb of DNA. Sequencing of the mdm2 gene reveale d three nucleotide differences that resulted in amino acid substitutio ns in the previously published mdm2 sequence. Sequencing of normal Bal bC/J DNA and the original cosmid clone isolated from the 3T3DM cell li ne revealed that they are identical, suggesting that the published seq uence is in error at these three positions. In addition, we analyzed t he expression pattern of mdm2 and found ubiquitous low-level expressio n throughout embryo development and in adult tissues. Analysis of mRNA hom numerous tissues for several mdm2 spliced variants that had been identified in the transformed 3T3DM cell line revealed that these vari ants could not be detected in the developing embryo or in adult tissue s. (C) 1996 Academic Press, Inc.