UP-REGULATION OF CARBONIC-ANHYDRASE ISOZYME-IV IN CNS MYELIN OF MICE GENETICALLY DEFICIENT IN CARBONIC-ANHYDRASE-II

Carbonic anhydrase (CA) II is the major CA isozyme in the brain, where it participates in acid-base homeostasis, fluid transport, and myelin synthesis. The CA II deficiency [CA(II)D] mutation in the mouse resul ts in structural changes in the glial cells in the CNS and in decrease d susceptibility to seizures, but no detectable changes in myelin yiel d and ultrastructure. We compared the CA isozymes in brain and spinal cord fractions, as well as in purified myelin, between CA(II)D and con trol mice. CA(II)D resulted in a much lower total CA specific activity in all tissues examined but in higher CA IV specific activities in so luble and membrane-associated fractions and pure myelin. Western blots of purified myelin showed a band corresponding to CA IV in CA(II)D mi ce. This band was weak or undetectable in myelin samples from normal m ice. Immunocytochemical staining demonstrated CA IV in oligodendrocyte s and myelinated tracts in normal mouse brains and stronger staining o f the same structures in brains of CA(II)D mutants. We conclude that C A(II)D mutation in the mouse up-regulates CNS CA IV. We speculate that this up-regulation could mitigate the effect of CA(II)D on myelin for mation and maintenance.