Lewis S E, Erickson R P, Barnett L B, Venta P J, Tashian R E
Research Triangle Institute, NC 27709.
Proc Natl Acad Sci U S A. 1988 Mar;85(6):1962-6. doi: 10.1073/pnas.85.6.1962.
Electrophoretic screening of (C57BL/6J x DBA/2J)F1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (CA II). Breeding tests showed that this trait was heritable and due to a null mutation at the Car-2 locus on chromosome 3. Like humans with the same inherited enzyme defect, animals homozygous for the new null allele are runted and have renal tubular acidosis. However, the prominent osteopetrosis found in humans with CA II deficiency could not be detected even in very old homozygous null mice. A molecular analysis of the deficient mice shows that the mutant gene is not deleted and is transcribed. The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus.
对用N-乙基-N-亚硝基脲处理过的雄性小鼠的（C57BL/6J×DBA/2J）F1代后代进行电泳筛选，发现一只小鼠缺乏父本的碳酸酐酶II（CA II）。繁殖试验表明，这一性状是可遗传的，并且是由于3号染色体上Car-2位点的无效突变所致。与具有相同遗传性酶缺陷的人类一样，新无效等位基因的纯合动物发育迟缓并患有肾小管酸中毒。然而，即使在非常年老的纯合无效小鼠中，也未检测到患有CA II缺乏症的人类中明显的骨硬化症。对缺陷小鼠的分子分析表明，突变基因未被删除且可转录。正常情况下在大多数组织中表达的CA II蛋白，在CA II缺陷小鼠的任何组织中通过免疫扩散分析均未检测到，这表明Car-2位点存在无义或错义突变。
