Deficiency of the tensin2 gene in the ICGN mouse:: an animal model for congenital nephrotic syndrome
Deficiency of the tensin2 gene in the ICGN mouse:: an animal model for congenital nephrotic syndrome
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DOI：
10.1007/s00335-005-0167-z
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发表时间：
2006-05-01
期刊：
影响因子：
2.5
通讯作者：
Agui, Takashi
中科院分区：
文献类型：
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作者：
Cho, A. -Ri;Uchio-Yamada, Kozue;Agui, Takashi
ICGN小鼠是肾病综合征（NS）的模型，其表现为蛋白尿、高脂血症和水肿。在这项研究中，我们试图确定负责NS的基因。通过对160只（ICGN × MSM）F-1 × ICGN回交后代的蛋白尿分析，我们发现ICGN小鼠的NS是由多个基因引起的。然后，我们进行了数量性状基因座（QTL）分析，并检测到一个QTL与一个非常高的LOD得分峰值在端粒区的Chr 15。通过分析位于QTL附近的22个基因的核苷酸序列，我们发现ICGN小鼠的tensin 2基因在外显子18处具有8个核苷酸的缺失突变，导致移码并在过早位置产生末端密码子。原位杂交和免疫组织化学分析显示，tensin 2在正常小鼠的足细胞和肾小管上皮细胞中表达，而在ICGN小鼠中不表达。这些数据提出了这样的可能性，即tensin 2基因的突变是导致ICGN小鼠NS的原因，并且tensin 2是正常肾功能的先决条件。
The ICGN mouse is a model for nephrotic syndrome (NS) which presents with proteinuria, hyperlipidemia, and edema. In this study we attempted to identify the gene(s) responsible for NS. By analyzing albuminuria in 160 (ICGN x MSM)F-1 x ICGN backcross progenies, we found that NS in the ICGN mouse is caused by more than one gene. We then performed a quantitative trait locus (QTL) analysis and detected a QTL with a very high LOD score peak in the telomeric region of Chr 15. By analyzing the nucleotide sequence of 22 genes located close to the QTL, we found that the tensin2 gene of the ICGN mouse possessed an 8-nucleotide deletion mutation in exon 18, leading to a frameshift and giving rise to a terminal codon at a premature position. Analyses of in situ hybridization and immunohistochemistry revealed that tensin2 was expressed in podocytes and tubular epithelial cells in normal mice but not in the ICGN mouse. These data raise the possibility that a mutation of the tensin2 gene is responsible for NS of the ICGN mouse and tensin2 is a prerequisite for the normal kidney function.