B6.D2-Car2ⁿ/J

Stock number: 001623
Product name: CA II-deficient
Research areas: Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Metabolism Research, Neurobiology Research

Description

These mice carry an ENU-induced mutation characterized by 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.

Detailed description

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.)

Development

DBA/2J males were treated with 200mg/kg N-ethyl-N-nitrosourea then mated to C57BL/6J females10 or more weeks after treatment. Blood and kidney samples from the offspring were assayed by isoelectric focusing and a male was identified that lacked the DBA/2J derived Car2^b band. The C57BL/6J derived Car2^a band was detected. This mutant male was backcrossed to C57BL/6J. Approximately one quarter of offspring from the mating of these F1 to their mutant father were found to have no Car2 bands in any of multiple tissues assayed. In 1988 this mutation was imported into the laboratory of Dr. Jane Barker at The Jackson Laboratory from Dr. Susan Lewis at Research Triangle Institute. Dr. Barker backcrossed it further onto C57BL/6J and in 1995 C57BL/6J females were bred with homozygous B6.D2-Car2ⁿ males, then at N19, and the resulting embryos were cryopreserved. (Lewis et al., 1988; Johnson and Lewis, 1981.)

Allele

Symbol: Car2ⁿ
Name: null
MGI accession ID: MGI:2135646
Generation method: Chemically induced (ENU)
Marker symbol: Car2
Marker name: carbonic anhydrase 2
Chromosome: 3
Strain of origin: DBA/2J
Molecular note: The result of ENU mutagenesis, the mutation at the Car2 locus is likely a nonsense or missense mutation. Molecular analysis shows that the mutant gene is not deleted but is transcribed. The CAR2 protein could not be detected by immunodiffusion analysis and Southern analysis indicates no detectable rearrangements or polymorphisms.