In human, CAR2 deficiencies can result in osteopetrosis, renal tubular acidosis, impaired growth, cerebral calcification, and mental retardation. Mice homozygous for Car2<n> do not display cerebral calcification or osteopetrosis, although medial calcification of small arteries has been found in several organs, most notably the male genital tract. The phenotype of these mice includes renal tubular acidosis, doubled urine output, increased urine pH and Cl-, decreased blood pH and HCO-3, phosphatemia, lower plasma bicarbonate, and a smaller body size. Despite smaller body weight, the kidneys are of normal size and plasma potassium and creatinine levels are normal. Type A and B intercalated cells of the kidney are severely depleted. Car2n homozygotes have reduced susceptibility to audiogenic and chemogenic seizures and hippocampal slices from homozygotes are more resistant to hypoxia than are those of wild type controls. Increased CAR4 levels, suggesting a compensation mechanism, have been found in oligodendrocytes and myelinated tracts. Successful liposome-delivered gene therapy has been performed on this mutant. (Lewis et al., 1988; Spicer et al., 1989; Brechue et al., 1991; Tashian, 1992; Velisek et al., 1993A and B, and 1995; Brion et al., 1994 and 1997; Breton et al.1995; Lai et al, 1998.)
