The murine nephrin gene is specifically expressed in kidney, brain and pancreas:: inactivation of the gene leads to massive proteinuria and neonatal death
The murine nephrin gene is specifically expressed in kidney, brain and pancreas:: inactivation of the gene leads to massive proteinuria and neonatal death
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DOI：
10.1093/hmg/10.1.1
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发表时间：
2001-01-01
影响因子：
3.5
通讯作者：
Tryggvason, K
中科院分区：
文献类型：
--
作者：
Putaala, H;Soininen, R;Tryggvason, K
通过同源重组将肾脏蛋白基因（NPHS1）灭活而产生的先天性肾病综合征（NPHS1）的小鼠模型是通过同源重组中的肾细胞中的，靶向构建体包含大肠杆菌大肠杆菌lacz基因作为NPHS1启动子的记者。纯合NPHS1纯合的小鼠的预期频率为25％。尽管出生时看似正常，但他们立即出现了大量的蛋白尿和水肿，并在24小时内死亡。无效小鼠的肾脏表现出扩大的弓箭手的空间，扩张的肾小管，足迹过程的脱落和缺乏裂隙膜片的缺失，这实际上是在人NPHS1患者中发现的。除了在肾小球足细胞中表达外，报告基因还在（+/-）和（ - / - ）小鼠的大脑和胰腺中表达。在大脑中，表达位于第四脑室的心室，发育中的脊髓，海马小脑和嗅球。在小脑中，在径向神经胶质细胞中看到了表达。在零小鼠的大脑中均未观察到解剖和形态异常。
A mouse model for congenital nephrotic syndrome (NPHS1) was generated by inactivating the nephrin gene (Nphs1) in embryonic stem cells by homologous recombination, The targeting construct contained the Escherichia coli lacZ gene as a reporter for the Nphs1 promoter. Mice homozygous for inactivated Nphs1 were born at an expected frequency of 25%. Although seemingly normal at birth, they immediately developed massive proteinuria and edema and died within 24 h. The kidneys of null mice exhibited enlarged Bowman's spaces, dilated tubuli, effacement of podocyte foot processes and absence of the slit diaphragm, essentially as found in human NPHS1 patients. In addition to expression in glomerular podocytes, the reporter gene was expressed in the brain and pancreas of (+/-) and (-/-) mice. In the brain, expression was localized to the Ventricular zone of the fourth ventricle, the developing spinal cord, cerebellum hippocampus and olfactory bulb. In the cerebellum, the expression was seen in radial glial cells. Neither anatomical nor morphological abnormalities were observed in the brains of null mice.