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Gene Review

Car4  -  carbonic anhydrase 4

Mus musculus

Synonyms: AW456718, CA IV, CA-IV, Ca4, Carbonate dehydratase IV, ...
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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


Biological context of Car4


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


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


  1. Catalytic properties of murine carbonic anhydrase IV. Hurt, J.D., Tu, C., Laipis, P.J., Silverman, D.N. J. Biol. Chem. (1997) [Pubmed]
  2. Colonic epithelial functional phenotype varies with type and phase of experimental colitis. Mizoguchi, E., Xavier, R.J., Reinecker, H.C., Uchino, H., Bhan, A.K., Podolsky, D.K., Mizoguchi, A. Gastroenterology (2003) [Pubmed]
  3. Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa. Perl, A., Qian, Y., Chohan, K.R., Shirley, C.R., Amidon, W., Banerjee, S., Middleton, F.A., Conkrite, K.L., Barcza, M., Gonchoroff, N., Suarez, S.S., Banki, K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Carbonic anhydrase IV and XIV knockout mice: roles of the respective carbonic anhydrases in buffering the extracellular space in brain. Shah, G.N., Ulmasov, B., Waheed, A., Becker, T., Makani, S., Svichar, N., Chesler, M., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Carbonic anhydrase IV on brain capillary endothelial cells: a marker associated with the blood-brain barrier. Ghandour, M.S., Langley, O.K., Zhu, X.L., Waheed, A., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  6. Effects of carbonic anhydrase II (CAII) deficiency on CNS structure and function in the myelin-deficient CAII-deficient double mutant mouse. Cammer, W., Zhang, H., Tansey, F.A. J. Neurosci. Res. (1995) [Pubmed]
  7. Isolation and expression of murine carbonic anhydrase IV. Hurt, J.D., Tu, C., Laipis, P.J. Protein Expr. Purif. (1998) [Pubmed]
  8. Molecular cloning of the mouse gene coding for carbonic anhydrase IV. Tamai, S., Cody, L.B., Sly, W.S. Biochem. Genet. (1996) [Pubmed]
  9. Carbonic anhydrase in mouse testis and epididymis; transfer of isozyme IV to spermatozoa during passage. Ekstedt, E., Holm, L., Ridderstråle, Y. J. Mol. Histol. (2004) [Pubmed]
  10. Expression of carbonic anhydrase IV in carbonic anhydrase II-deficient mice. Brion, L.P., Cammer, W., Satlin, L.M., Suarez, C., Zavilowitz, B.J., Schuster, V.L. Am. J. Physiol. (1997) [Pubmed]
  11. Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II. Brion, L.P., Suarez, C., Zhang, H., Cammer, W. J. Neurochem. (1994) [Pubmed]
  12. Acid-base effects on electrolyte transport in CA II-deficient mouse colon. Goldfarb, D.S., Sly, W.S., Waheed, A., Charney, A.N. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
  13. Expression of carbonic anhydrases II, IV, VII, VIII and XII in rat brain after kainic acid induced status epilepticus. Halmi, P., Parkkila, S., Honkaniemi, J. Neurochem. Int. (2006) [Pubmed]
  14. Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination. Stams, T., Chen, Y., Boriack-Sjodin, P.A., Hurt, J.D., Liao, J., May, J.A., Dean, T., Laipis, P., Silverman, D.N., Christianson, D.W. Protein Sci. (1998) [Pubmed]
  15. Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter. Alvarez, B.V., Loiselle, F.B., Supuran, C.T., Schwartz, G.J., Casey, J.R. Biochemistry (2003) [Pubmed]
  16. Expression of Membrane-bound Carbonic Anhydrases IV, IX, and XIV in the Mouse Heart. Scheibe, R.J., Gros, G., Parkkila, S., Waheed, A., Grubb, J.H., Shah, G.N., Sly, W.S., Wetzel, P. J. Histochem. Cytochem. (2006) [Pubmed]
  17. Human growth hormone transgene expression increases the biomechanical structural properties of mouse vertebrae. Steinke, B., Patwardhan, A.G., Havey, R.M., King, D. Spine. (1999) [Pubmed]
  18. Expression of membrane-associated carbonic anhydrase isoforms IV, IX, XII, and XIV in the rabbit: induction of CA IV and IX during maturation. Purkerson, J.M., Schwartz, G.J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  19. A conditionally immortalized cell line from murine proximal tubule. Loghman-Adham, M., Rohrwasser, A., Helin, C., Zhang, S., Terreros, D., Inoue, I., Lalouel, J.M. Kidney Int. (1997) [Pubmed]
  20. Expression of carbonic anhydrase IV in mouse placenta. Rosen, O., Suarez, C., Schuster, V.L., Brion, L.P. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
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