Brueckner M, D'Eustachio P, Horwich A L
Department of Pediatric Cardiology, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1989 Jul;86(13):5035-8. doi: 10.1073/pnas.86.13.5035.
Inherited single gene defects have been identified in both humans and mice that lead to loss of developmental control over the left-right asymmetry of the heart and viscera. In mice the recessively inherited mutation iv leads to such apparent loss of control over situs: 50% of iv/iv mice exhibit situs inversus and 50% exhibit normal situs. The affected gene product has not been identified in these animals. To study the normal function of iv, we have taken an approach directed to the gene itself. As a first step, we have mapped iv genetically, by examining its segregation in backcrosses with respect to markers defined by restriction fragment length polymorphisms. The iv locus lies 3 centimorgans (cM) from the immunoglobulin heavy-chain constant-region gene complex (Igh-C) on chromosome 12. A multilocus map of the region suggests the gene order centromere-Aat (alpha 1-antitrypsin gene complex)-(11 cM)-iv-(3 cM)-Igh-C-(1 cM)-Igh-V (immunoglobulin heavy-chain variable-region gene complex).
在人类和小鼠中都已鉴定出导致心脏和内脏左右不对称发育控制丧失的单基因缺陷。在小鼠中,隐性遗传突变iv会导致这种明显的位置控制丧失:50%的iv/iv小鼠表现出内脏反位,50%表现出正常位置。在这些动物中尚未鉴定出受影响的基因产物。为了研究iv的正常功能,我们采取了针对该基因本身的方法。第一步,我们通过检查其在与由限制性片段长度多态性定义的标记进行回交中的分离情况,对iv进行了基因定位。iv基因座位于12号染色体上免疫球蛋白重链恒定区基因复合体(Igh-C)3厘摩(cM)处。该区域的多位点图谱表明基因顺序为着丝粒-Aat(α1-抗胰蛋白酶基因复合体)-(11 cM)-iv-(3 cM)-Igh-C-(1 cM)-Igh-V(免疫球蛋白重链可变区基因复合体)。