Use of carbonic anhydrase II-deficient mice in uncovering the cellular location of membrane-associated isoforms

Abstract

As long ago as 1960, plasma membranes and cell organelles were shown by Karler and Woodbury to exhibit carbonic anhydrase (CA) (carbonate hydrolyase; EC: 4.1.1.) activity. For tissues like kidney (Wistrand and Knuttilla, 1989), lung (Waheed et al., 1992), blood vessels (Ghandour et al., 1992), and skeletal muscle (Gros, 1991), this activity has since been shown to originate from a membrane-bound integral hydrophic isoform of CA, now designated as CA IV (cf. Sly and Hu, 1995). The CA IV activity of these tissues can be detected by the cobalt-phosphate histochemical method (cf. Ridderstråle, 1991). However, this method also detects CA activity associated with cell membranes of renal distal tubules, neuroretina, choroid epithelium, ciliary epithelium, cornea and brain (Ridderstråle et al., 1992, 1994; Ridderstråle and Wistrand, 1998), where CA IV has been claimed not to be present (Brown et al., 1990; Hageman et al., 1991; Ghandour et al., 1992). Moreover, the histochemical technique occasionally localizes CA-activity to cell nuclei, and mitochondria (cf. Ridderstråle, 1991).