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

Abstract

The intercellular adhesion molecule CEACAM1, also known as C-CAM1 (where CAM is cell-adhesion molecule), can function as a tumour suppressor in several carcinomas, including those of the prostate, breast, bladder and colon. This suggests that CEACAM1 may play an important role in the regulation of normal cell growth and differentiation. However, there is no direct evidence to support this putative function of CEACAM1. To elucidate its physiological 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 identified in the mouse. Our sequence analysis revealed that the genes encoded nine exons and spanned approx. 16-17 kb (Ceacam1) and 25 kb (Ceacam2). The genes were highly similar (79.6%). The major differences in the protein-coding regions were located in exons 2, 5 and 6 (76.9%, 87.0% and 78.5% similarity respectively). In addition, introns 2, 5 and 7 were also significantly different, being 29.7%, 59.8% and 64.5% similar respectively. While most of these differences were due to nucleotide substitutions, two insertions of 418 and 5849 bp occurred in intron 2 of Ceacam2, and another two insertions of 1384 and 197 bp occurred in introns 5 and 7 respectively. To determine whether functional redundancy exists between Ceacam1 and Ceacam2, we examined their expression in 16 mouse tissues by using semi-quantitative reverse transcription-PCR. As in human and rat, in the mouse Ceacam1 mRNA was highly abundant in the liver, small intestine, prostate and spleen. In contrast, Ceacam2 mRNA was only detected in kidney, testis and, to a lesser extent, spleen. Reverse transcription-PCR using testis RNA indicated that Ceacam2 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 the 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.

Liver-specific reconstitution of CEACAM1 reverses the metabolic abnormalities caused by its global deletion in male mice

“…Consistent with the predominant expression of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in the liver [5], we have shown that CEACAM1 provides a post-receptor mechanistic underpinning of how impaired insulin clearance causes chronic hyperinsulinaemia [6–8]. Upon its phosphorylation by the insulin receptor [9], CEACAM1, a plasma membrane glycoprotein, increases the rate of receptor-mediated insulin uptake into the hepatocyte and its targeting to the degradation pathways by taking part in the insulin receptor endocytosis complex [10].…”

“…r Cc1 levels were negligible in the hypothalamus of all genotypes. Neither r Cc1 nor m Cc1 were detected in the WAT of any genotype [5]. Nevertheless, CEACAM1 may still be targeted to an undetermined extrahepatic cell/tissue.…”

“…5c). Of note, because the cytoplasmic domain of CEACAM2 shares a high homology with that of CEACAM1, in particular at the tyrosine site [5], p-CEACAM1 antibodies also recognise p-CEACAM2 which is highly expressed in the hypothalamus [27]. To investigate whether the increase in hypothalamic FASN activity contributes to hyperphagia, we examined the effect of C75, a FASN inhibitor [28], on daily food intake.…”

Ouabain and Insulin Induce Sodium Pump Endocytosis in Renal Epithelium

“…CEACAM2, a highly homologous related protein to CEACAM1, is the predominant protein in murine kidney 20 . With CEACAM proteins being expressed in kidney proximal tubules, we evaluated the role of CEACAM2 in regulating blood pressure following salt loading.…”

Structure and evolution of the mouse pregnancy-specific glycoprotein (Psg) gene locus

“…Conversely, a small number of human and mouse CEACAM variants lack a membrane anchor and are secreted. Membrane-anchored CEACAMs are widely expressed during embryonic development and in adult tissues, and are implicated in carcinogenesis, angiogenesis and regulation of immune functions [13,14]. In contrast, PSGs and some CEACAMs are expressed almost exclusively in trophoblasts of the haemochorial placenta of rodents and primates [4,5,15].…”