Disease relevance of Car9

• Gastric hyperplasia in mice with targeted disruption of the carbonic anhydrase gene Car9 [1].
• Transmembrane carbonic anhydrase IX (CA IX) is frequently expressed in human tumours in response to hypoxia and may serve as a tumour marker and therapeutic target [2].
• In the pulmonary metastatic model, a similar number of metastases was noted after inoculation of RENCA and RENCA/CA-IX [3].
• RENCA/carbonic anhydrase-IX: a murine model of a carbonic anhydrase-IX-expressing renal cell carcinoma [3].
• METHODS: A retrovirus encoding the human CA-IX gene was used to transduce the murine RCC line, RENCA [3].

High impact information on Car9

• CONCLUSIONS: Phenotypic consequences of the Car9 null mutation show the important role of CA IX in morphogenesis and homeostasis of the glandular gastric epithelium via the control of cell proliferation and differentiation [1].
• Correspondingly, CA IX-deficient mice had normal gastric pH, acid secretion, and serum gastrin levels [1].
• Carbonic anhydrase 9 (CA9) is a transmembrane protein overexpressed in a wide variety of tumor types and induced by hypoxia [4].
• Car9 mRNA and CA IX protein expression levels were up-regulated about 2.5- and 3.6-fold, respectively, in the stomach of the Car2-/- mice [5].
• Similar findings were noted with another hypoxia-inducible gene, carbonic anhydrase IX [6].

Biological context of Car9

• Stomach samples were collected from 40 Car 9(-/-) knockout mice and 37 wildtype littermates, and the tissue sections were examined for histology [7].
• RESULTS: Immunohistochemistry demonstrated that both CA IX and XII are present in several tissues of the developing mouse embryo during organogenesis [8].
• In vivo growth kinetics and CA-IX expression were compared between RENCA and RENCA/CA-IX using heterotopic, metastatic, and orthotopic models [3].

Anatomical context of Car9

• Therefore, the unique subcellular localization of CA IX and CA XIV in cardiac myocytes suggests different functions of both enzymes in excitation-contraction coupling [9].
• Inactivation of the VHL gene resulted in hypoxia-inducible factor (HIF)-1alpha stabilization and induction of its target genes, VEGF and CAIX, in mouse embryonic fibroblasts (MEFs) [10].
• Moreover, the availability of the MAbs specific for distinct antigenic regions on two separate extracellular domains offers an opportunity to elaborate a sensitive assay that could be particularly important for CA IX detection in body fluids of cancer patients [2].
• Reverse transcriptase PCR analyses surprisingly revealed strong signals for CA IX mRNA in the kidney and skeletal muscle, while the IHC and Western blotting showed no or weak signals for the corresponding protein [11].
• In a recently described knockout mouse model for CA IX deficiency, the only phenotypic abnormalities were limited to the gastric mucosa, while no changes were observed in the other tissues known to express CA IX in rats and humans [11].

Other interactions of Car9

• CA XIV is predominantly localized in the longitudinal SR, whereas CA IX is mainly expressed in the terminal SR/t-tubular region [9].
• Staining for CA IX revealed a relatively wide distribution pattern with moderate signals in the brain, lung, pancreas and liver and weak signals in the kidney and stomach [8].

References