Mapping quantitative trait loci for proteinuria-induced renal collagen deposition
Mapping quantitative trait loci for proteinuria-induced renal collagen deposition
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DOI：
10.1038/ki.2008.7
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发表时间：
2008-05-01
影响因子：
19.6
通讯作者：
Okada, H.
中科院分区：
文献类型：
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作者：
Kato, N.;Watanabe, Y.;Okada, H.
慢性肾脏病的进展是一个受遗传因素影响的复杂过程。蛋白尿是功能恶化的预测因子，也是肾实质损伤和间质纤维化导致疾病进展的加速器。为了确定可能介导蛋白尿引起的肾纤维化的遗传成分，我们绘制了影响两种小鼠品系表型的位点，这两种小鼠品系在蛋白尿诱导的肾 I 型胶原 (COLI) 沉积方面存在差异。 129S1/svImJ 和 C57BL/6J 小鼠中的 I 型胶原蛋白沉积在测试品系之间存在显着差异。我们对 120 只半肾切除 (129S1/svImJ x C57BL/6J) F1 x 129S1/svImJ 回交小鼠进行了回交，这些小鼠负载了牛血清白蛋白，导致蛋白尿和肾脏 COLI 沉积。进行了数量性状位点 (QTL) 作图，我们的分析确定了与 Chr 2 上 D2Mit224 附近 87cM 处峰值为 87cM（优势对数：2.41）的肾脏 COLI 沉积的一个提示性关联。计算机分析发现了 9 个候选基因。因此，尽管还需要更多的研究，但这些 QTL 为随后的基因发现提供了初步线索，这可能有助于解开肾纤维化的遗传学。
The progression of chronic kidney disease is a complex process influenced by genetic factors. Proteinuria is a predictor of functional deterioration and an accelerator of disease progression through renal parenchymal damage and interstitial fibrosis. To determine genetic components that might mediate renal fibrosis due to proteinuria, we mapped loci influencing the phenotype of two mouse strains differing in proteinuria-induced renal type I collagen ( COLI) deposition. Collagen I deposition in 129S1/svImJ and C57BL/6J mice differs significantly among tested strains. We backcrossed 120 hemi-nephrectomized ( 129S1/svImJ x C57BL/ 6J) F1 x 129S1/svImJ backcrossed mice loaded with bovine serum albumin giving rise to proteinuria and renal COLI deposition. Quantitative trait loci (QTL) mapping was performed and our analysis identified one suggestive linkage for renal COLI deposition peaking at 87cM near D2Mit224 ( logarithm of odds: 2.41) on Chr 2. In silico analysis uncovered nine candidate genes. Hence, although more studies are needed, these QTL provide an initial cue to subsequent gene discovery, which might help unravel the genetics of renal fibrosis.