Differences in tissue-specific and embryonic expression of mouse Ceacam1 and Ceacam2 genes

The intercellular adhesion molecule CEACAM1, also known as C-CAM1 (where CA M is cell-adhesion molecule), can function as a tumour suppressor in severa l carcinomas, including those of the prostate, breast, bladder and colon. T his suggests that CEACAM1 may play an important role in the regulation of n ormal cell growth and differentiation. However, there is no direct evidence to support this putative function of CEACAM1. To elucidate its physiologic al function by targeted gene deletion, we isolated the Ceacam genes from a mouse 129 Sv/Ev library. Although there is only one Ceacam1 gene in humans and one in rats, two homologous genes (Ceacam1 and Ceacam2) have been ident ified in the mouse. Our sequence analysis revealed that the genes encoded n ine exons and spanned approx. 16-17 kb (Ceacam1) and 25 kb (Ceacam2). The g enes were highly similar (79.6 %) The major differences in the protein-codi ng regions were located in exons 2, 5 and 6 (76.9 %, 87.0 % and 78.5 % simi larity respectively). In addition, introns 2. 5 and 7 were also significant ly different, being 29.7 %, 59.8 % and 64.5 % similar respectively. While m ost of these differences were due to nucleotide substitutions, two insertio ns of 418 and 5849 bp occurred in intron 2 of Ceacam2. and another two inse rtions of 1384 and 197 bp occurred in introns 5 and 7 respectively. To dete rmine whether functional redundancy exists between Ceacam1 and Ceacam2, we examined their expression in 16 mouse tissues by using semi-quantitative re verse transcription-PCR, As in human and rat, in the mouse Ceacam1 mRNA was highly abundant in the liver, small intestine, prostate and spleen. In con trast, Cencam2 mRNA was only detected in kidney, testis and, to a lesser ex tent, spleen. Reverse transcription-PCR using testis RNA indicated that Cea cam2 in the testis is an alternatively spliced form containing only exons 1 , 2, 5, 6, 8 and 9. In the mouse embryo, Ceacam1 mRNA was detected at day 8 .5, disappeared between days 9.5 and 12.5, and re-appeared at day 19. On th e other hand, no Ceacam2 mRNA was detected throughout embryonic development . The different tissue expression patterns and regulation during embryonic development suggest that the CEACAM1 and CEACAM2 proteins, although highly similar, may have different functions both during mouse development and in adulthood.