Genetic identification of two major modifier loci of polycystic kidney disease progression in pcy mice.
Genetic identification of two major modifier loci of polycystic kidney disease progression in pcy mice.
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pcy 小鼠多囊肾病进展的两个主要修饰基因座的遗传鉴定。
DOI：
10.1172/jci119724
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Olsen,P
中科院分区：
文献类型：
--
作者：
Woo,DD;Nguyen,DK;Khatibi,N;Olsen,P
与近交系动物中的统一疾病进展不同，人类家族中的多囊肾病（PKD）进展可能高度可变。这可能是由于环境或遗传因素或两者兼而有之。为了确定PKD的严重程度是否可以受到修饰基因的影响，我们进行了DBA/2-pcy/pcy和Mus m.涉及3，105只6周龄F2小鼠。在该交叉中观察到PKD严重程度的巨大差异。此外，23/ 800的表型正常小鼠是pcy/pcy基因型。这些结果表明，PKD的进展在pcy/ pcy小鼠是一个数量性状，强烈调节修饰基因。对114只pcy/pcy小鼠（68只轻度PKD，46只重度PKD）进行全基因组数量性状基因座定位，发现MOP 1和MOP 2两个基因座强烈调节PKD进展。MOP 1（D4 Mit 111时最大LOD评分= 10.3）和MOP 2（D16 Mit 1时最大LOD评分= 13.8）分别占表型方差的36.7%和46.8%。双因素方差分析的表型和基因型的所有673 pcy/pcy小鼠从我们的交叉表明，MOP 1和MOP 2等位基因调节PKD的进展，在一个复杂的添加剂的方式。这些新的修饰位点的表征可能提供额外的见解多囊肾疾病的发病机制。
Unlike the uniform disease progression in inbred animals, polycystic kidney disease (PKD) progression within human families can be highly variable. This may be due to environmental or genetic factors or both. To determine if PKD severity can be influenced by modifier genes, we carried out an intercross between DBA/2-pcy/pcy and Mus m. castaneous involving 3,105 6-wk-old F2 mice. Large differences in PKD severity were observed in this cross. In addition, 23/ 800 phenotypically normal mice were pcy/pcy genotypically. These results demonstrated that PKD progression in pcy/ pcy mice is a quantitative trait that is strongly modulated by modifier genes. Whole genome quantitative trait loci mapping of 114 selected pcy/pcy mice (68 with the mild PKD and 46 with severe PKD) identified two loci, MOP1 and MOP2 that strongly modulate PKD progression. MOP1 (max LOD score = 10.3 at D4Mit111) and MOP2 (max LOD score = 13.8 at D16Mit1) accounted for 36.7 and 46.8% of the phenotypic variance, respectively. Two-factor ANOVA of the phenotypes and genotypes of all 673 pcy/pcy mice from our cross indicated that MOP1 and MOP2 alleles regulate PKD progression in a complex additive manner. Characterization of these novel modifying loci may provide additional insights into the pathogenesis of polycystic kidney diseases.