Gene expression profiling in the submandibular gland, stomach, and duodenum of CAVI-deficient mice

Abstract

Carbonic anhydrase VI (CAVI) is the only secreted isozyme of the α-carbonic anhydrase family, which catalyzes the reversible reaction [Formula in text]. It appears that CAVI protects teeth and gastrointestinal mucosa by neutralizing excess acidity. However, the evidence for this physiological function is limited, and CAVI may have additional functions that have yet to be discovered. To explore the functions of CAVI more fully, we generated Car6 (-/-) mice and analyzed Car6 (-/-) mutant phenotypes. We also examined transcriptomic responses to CAVI deficiency in the submandibular gland, stomach, and duodenum of Car6 (-/-) mice. Car6 (-/-) mice were viable and fertile and had a normal life span. Histological analyses indicated a greater number of lymphoid follicles in the small intestinal Peyer's patches. A total of 94, 56, and 127 genes were up- or down-regulated in the submandibular gland, stomach, and duodenum of Car6 (-/-) mice, respectively. The functional clustering of differentially expressed genes revealed a number of altered biological processes. In the duodenum, the significantly affected biological pathways included the immune system process and retinol metabolic processes. The response to oxidative stress and brown fat cell differentiation changed remarkably in the submandibular gland. Notably, the submandibular gland, stomach, and duodenum shared one important transcriptional susceptibility pathway: catabolic process. Real-time PCR confirmed an altered expression in 14 of the 16 selected genes. The generation and of Car6 (-/-) mice and examination of the effects of CAVI deficiency on gene transcription have revealed several affected clusters of biological processes, which implicate CAVI in catabolic processes and the immune system response.

Nuclear carbonic anhydrase 6B associates with PRMT5 to epigenetically promote IL-12 expression in innate response

“…Car6 −/− mice and Car6-sufficient littermate (Car6 +/+ ) mice were fertile and normal in size. They were viable and normal, consistent with previous reports (16). FACS analysis showed no difference in immune cells including CD19 + B cells, CD4 + T cells, CD8 + T cells, NK cells, and macrophages between Car6 +/+ and Car6 −/− mice (Fig.…”

“…We wondered whether the underlying mechanism for Car6-b selectively promotes IL-12 expression in innate response. CA-VI A is secreted into saliva to maintain pH homeostasis by its CA enzyme activity (16), and CA-VI B also contains this enzyme domain. We wondered whether the pH of cytoplasm and the nucleus of PM might be involved in Car6-bmediated promotion of IL-12 expression.…”

Variations in the bitterness perception-related genes TAS2R38 and CA6 modify the risk for colorectal cancer in Koreans

“…Finally, CAVI is likely linked to the immune response, which may be associated with carcinogenic etiology. In a murine CAVI-deficient model, silenced CAVI expression resulted in the perturbation of lymphoid follicles in the intestinal Peyer's patches and the up- and down-regulation of 127 genes, which were mostly involved in catabolic processes in the duodenum [18]. Variant CAVI may lead to the perturbation of the immune system and related carcinogenic mechanisms and may, therefore, be linked to the risk of CRC.…”

“…Carbonic anhydrase VI (CAVI, gustin, CA6 ), a zinc-containing salivary protein, is known to be involved in PROP-mediated bitterness sensation [16–18]. CA family proteins play a central role in pH regulation and electrolyte balance, and CAVI is known to be a trophic factor for the growth and development of taste buds and bitterness sensation [19, 20].…”

Expression of Carbonic Anhydrase I in Motor Neurons and Alterations in ALS

“…CA6 is initially described as a gustatory protein and highly expressed in the salivary and mammary glands. Mice deficient in both copies of the CA6 gene prefer bitter taste [36,37]. Polymorphism in the human CA6 gene was also linked to bitter taste perception [37].…”