Disease relevance of Car4

• A cDNA encoding the murine carbonic anhydrase IV (mCA IV) gene, modified to resemble a form of mature human carbonic anhydrase IV (Okuyama, T., Waheed, A., Kusumoto, W., Zhu, X. L., and Sly, W. S. (1995) Arch. Biochem. Biophys. 320, 315-322), was expressed in Escherichia coli [1].
• Among the detoxification-associated molecules, carbonic anhydrase IV was specifically down-regulated in CEC of Th2- but not Th1-mediated colitis [2].
• Reduced forward progression of TAL-deficient spermatozoa is associated with diminished mitochondrial reactive oxygen intermediate production and Ca(2+) levels, intracellular acidosis, and compensatory down-regulation of carbonic anhydrase IV and overexpression of CD38 and gamma-glutamyl transferase [3].

High impact information on Car4

• To examine the relative importance of these two isozymes in this and other physiological functions attributed to extracellular CAs, we produced CA IV and CA XIV knockout (KO) mice by targeted mutagenesis and the doubly deficient CA IV/XIV KO mice by intercrossing the individual null mice [4].
• Thus, both CA IV and CA XIV contribute to extracellular buffering in the central nervous system, although CA IV appears to be more important in the hippocampus [4].
• Carbonic anhydrase IV and XIV knockout mice: roles of the respective carbonic anhydrases in buffering the extracellular space in brain [4].
• Results of immunohistochemistry and immunoelectron microscopy on sections from rat and mouse brain are presented that show the distribution of CA IV to be quite distinct from that of CA II [5].
• Carbonic anhydrase IV on brain capillary endothelial cells: a marker associated with the blood-brain barrier [5].

Biological context of Car4

• These results establish CA IV as a cytochemical marker associated with the blood-brain barrier and suggest an important role for CA IV in CO2 and HCO3- homeostasis in brain [5].
• Like the brains of Car-2n mutants, those of double mutants (MldCar-2n) were deficient in mRNA and protein for CAII and showed upregulation of a different isozyme, CAIV [6].
• A 1193-bp cDNA containing the complete murine carbonic anhydrase IV coding sequence was isolated from a Balb/c kidney cDNA library [7].
• The nucleotide sequence alignment between mouse and rat CA IV cDNAs reveals 84% identity [8].
• A function in HCO3- transport during sperm capacitation at fertilization is suggested for the CA IV found in spermatozoa [9].

Anatomical context of Car4

• Western blot analysis showed higher expression of CA IV immunoreactive protein in renal membranes from males than in those from females [10].
• Western blots of purified myelin showed a band corresponding to CA IV in CA(II)D mice [11].
• Immunocytochemical staining demonstrated CA IV in oligodendrocytes and myelinated tracts in normal mouse brains and stronger staining of the same structures in brains of CA(II)D mutants [11].
• In Car-2(0) mouse colonic mucosa, total CA activity was reduced 80% and cytosolic CA I and membrane-bound CA IV activities were not increased [12].
• The expression of CA IV, CA VII and CA-RP VIII was somewhat similar: they were expressed in the cortex, hippocampus and midbrain structures and their expression did not change after the kainic acid treatment [13].

Associations of Car4 with chemical compounds

• CA IV is expressed on and is limited to the luminal surface of endothelial cells of cerebral capillaries [5].
• The activity of purified recombinant carbonic anhydrase IV was highly resistant to sodium dodecyl sulfate, as is the native enzyme [7].
• After rapid dilution of washed, guanidine hydrochloride-denatured inclusion bodies into a glutathione-, l-arginine-containing renaturation buffer, an active carbonic anhydrase IV at yields of 3-4 mg/liter was easily purified from cultures expressing the form lacking the N-terminal targeting sequence and 26 C-terminal residues [7].
• Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to plasma membrane surfaces by a phosphatidylinositol glycan linkage [14].
• Carbonic anhydrase IV (CAIV), which is also present in these tissues, is glycosylphosphatidyl inositol-anchored to the outer surface of the plasma membrane where it catalyzes the hydration-dehydration of CO(2)/HCO(3)(-) [15].

Other interactions of Car4

• Expression of CA IX in the CA IV/CA XIV knockout animals was further confirmed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry [16].
• Expression of carbonic anhydrase IV in carbonic anhydrase II-deficient mice [10].
• CA(II)D resulted in a much lower total CA specific activity in all tissues examined but in higher CA IV specific activities in soluble and membrane-associated fractions and pure myelin [11].
• METHODS: Compression tests were performed on individual caudal vertebrae (Ca4, Ca5, Ca6) obtained from male and female mice from two transgenic lines (TG420 and TG450) and nontransgenic control mice [17].
• CA IV and CA XII are important kidney isoforms [18].

Analytical, diagnostic and therapeutic context of Car4

• Molecular cloning of the mouse gene coding for carbonic anhydrase IV [8].
• By electron microscopy, tsMPT cells are polarized and show microvilli at their apical surface. tsMPT cells express brush border enzymes gamma-glutamyl transpeptidase and carbonic anhydrase IV [19].
• The expression of CA IV mRNA on Northern blots tripled from day 11 to day 15 and then remained stable until the end of pregnancy [20].

References