CLONING OF THE MOUSE HOMOLOG OF THE DELETED IN COLORECTAL-CANCER GENE(MDCC) AND ITS EXPRESSION IN THE DEVELOPING MOUSE EMBRYO

Loss of DCC gene expression has now been demonstrated in a wide variet y of metastatic cancers. Here we present the nucleotide sequence and p redicted amino acid sequence of mouse DCC, Mouse and human DCC share 9 6% identity at the amino acid level, Analysis of DCC mRNA expression t hroughout the mid to late stages of gestation in the mouse, demonstrat ed that DCC mRNA is expressed at significantly higher levels in the de veloping mouse embryo than in any adult tissue, In addition, we show t hat an embryo-specific, alternatively spliced, form of DCC is expresse d in day 9.5 through day 18.5 embryos. The expression of both alternat ively spliced forms of DCC is developmentally regulated such that the embryonic form of DCC predominates in day 9.5 and 10.5 embryos. In the later stage embryos the expression of this alternatively spliced form of DCC is down-regulated with respect to that of the adult form, Whol e-mount in situ hybridization of day 11.5 mouse embryos revealed that DCC mRNA is expressed at high levels in the developing brain and the n eural tube, However, no DCC mRNA could be detected in any other embryo nic tissue at this stage of development, These observations suggest th at during embryogenesis DCC may play a pivotal role in the development of the central nervous system.