Guay-Woodford L M, Bryda E C, Christine B, Lindsey J R, Collier W R, Avner E D, D'Eustachio P, Flaherty L
Department of Medicine, University of Alabama at Birmingham, USA.
Kidney Int. 1996 Oct;50(4):1158-65. doi: 10.1038/ki.1996.423.
Numerous mouse models of polycystic kidney disease (PKD) have been described. All of these diseases are transmitted as single recessive traits and in most, the phenotypic severity is influenced by the genetic background. However, based on their genetic map positions, none of these loci appears to be allelic and none are candidate modifier loci for any other mouse PKD mutation. Previously, we have described the mouse bpk mutation, a model that closely resembles human autosomal recessive polycystic kidney disease. We now report that the bpk mutation maps to a 1.6 CM interval on mouse Chromosome 10, and that the renal cystic disease severity in our intersubspecific intercross progeny is influenced by the genetic background. Interestingly, bpk co-localizes with jcpk, a phenotypically-distinct PKD mutation, and complementation testing indicates that the bpk and jcpk mutations are allelic. These data imply that distinct PKD phenotypes can result from different mutations within a single gene. In addition, based on its map position, the bpk locus is a candidate genetic modifier for jck, a third phenotypically-distinct PKD mutation.
已经描述了许多多囊肾病（PKD）的小鼠模型。所有这些疾病都作为单隐性性状遗传，并且在大多数情况下，表型严重程度受遗传背景影响。然而，根据它们在遗传图谱上的位置，这些基因座似乎都不是等位基因，也没有一个是任何其他小鼠PKD突变的候选修饰基因座。此前，我们已经描述了小鼠bpk突变，这是一种与人类常染色体隐性多囊肾病非常相似的模型。我们现在报告，bpk突变定位于小鼠第10号染色体上1.6厘摩的区间，并且我们种间杂交后代的肾囊性疾病严重程度受遗传背景影响。有趣的是，bpk与jcpk共定位，jcpk是一种表型不同的PKD突变，互补试验表明bpk和jcpk突变是等位基因。这些数据表明，单个基因内的不同突变可导致不同的PKD表型。此外，根据其图谱位置，bpk基因座是jck的候选遗传修饰基因，jck是第三种表型不同的PKD突变。
