Lith6:: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains
Lith6:: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains
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DOI：
10.1194/jlr.m300149-jlr200
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发表时间：
2003-09-01
影响因子：
6.5
通讯作者：
Paigen, B
中科院分区：
文献类型：
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作者：
Lyons, MA;Wittenburg, H;Paigen, B
复杂的遗传基础决定了个体在环境因素的影响下易患胆固醇胆结石。本研究利用CAST/Ei（易感）和DBA/2J（抗性）自交系间的数量性状位点/位点（QTL）分析，确定了这些菌株所具有的胆结石易感性（Lith）基因子集。本研究对两种性别的亲代和第一代子代小鼠以及雄性杂交后代喂食致石饮食后的胆结石形成情况进行了评估。采用多区间映射的形式进行了联动分析。一个重要的QTL与Lith1[染色体（chr） 2,50 cM]共定位，这是一个先前发现的位点。值得注意的是，新的QTL被检测到并命名为Lith10 (chr 6,4 cM), Lith6 （chr 6,54 cM）和Lith11 （chr 8,58 cM）。统计和遗传分析表明，Lith6由两个接近的QTL组成。我们的分子和遗传数据支持过氧化物酶体增殖体激活受体γ (Pparg)和Slc21a1，分别编码Pparg和基底外侧胆汁酸转运体Slc21a1 （Slc21a1/Oatp1）作为Lith6的潜在基因。
A complex genetic basis determines the individual predisposition to develop cholesterol gallstones in response to environmental factors. We employed quantitative trait locus/loci (QTL) analyses of an intercross between inbred strains CAST/Ei (susceptible) and DBA/2J (resistant) to determine the subset of gallstone susceptibility (Lith) genes these strains possess. Parental and first filial generation mice of both genders and male intercross offspring were evaluated for gallstone formation after feeding a lithogenic diet. Linkage analysis was performed using a form of multiple interval mapping. One significant QTL colocalized with Lith1 [chromosome (chr) 2, 50 cM], a locus identified previously. Significantly, new QTL were detected and named Lith10 (chr 6, 4 cM), Lith6 (chr 6, 54 cM), and Lith11 (chr 8, 58 cM). Statistical and genetic analyses suggest that Lith6 comprises two QTL in close proximity. Our molecular and genetic data support the candidacy of peroxisome proliferator-activated receptor gamma (Pparg) and Slc21a1, encoding Pparg, and the basolateral bile acid transporter SLC21A1 (Slc21a1/Oatp1), respectively, as genes underlying Lith6.