Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models
Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models
复制标题
DOI：
10.1152/ajprenal.00213.2006
复制
发表时间：
2007-05-01
影响因子：
4.2
通讯作者：
Wolf, Eckhard
中科院分区：
文献类型：
--
作者：
Aigner, Bernhard;Rathkolb, Birgit;Wolf, Eckhard
肾脏疾病导致代谢产物的尿排泄失败。在慕尼黑乙基亚硝基脲（ENU）小鼠诱变项目中，该项目是在C3 H近交遗传背景下进行的，对超过15，000个G1后代和500个G3谱系的血液样品进行了临床化学参数改变的筛选。我们确定了44只动物始终表现出血浆尿素浓度升高。对23只小鼠改变的表型进行遗传分析，建立了5个突变系。在这些品系中，两种性别均受到影响。突变体的尿尿素水平降低。此外，大多数突变体显示血浆肌酐水平升高和尿肌酐水平降低。对5个突变株系的肾脏进行病理学研究发现了广泛的变化，从肉眼和光镜下肾脏无变化到肾脏重量/体重比降低、肾盂扩张和严重肾小球病变.因此，在大规模ENU小鼠诱变项目中筛选升高的血浆尿素水平导致小鼠品系的成功建立，所述小鼠品系是参与尿素排泄的机制的分子研究的有价值的工具或代表了令人感兴趣的肾脏疾病模型。
Kidney diseases lead to the failure of urinary excretion of metabolism products. In the Munich ethylnitrosourea ( ENU) mouse mutagenesis project, which is done on a C3H inbred genetic background, blood samples of more than 15,000 G1 offspring and 500 G3 pedigrees were screened for alterations in clinical- chemical parameters. We identified 44 animals consistently exhibiting increased plasma urea concentrations. Transmission analysis of the altered phenotype of 23 mice to subsequent generations led to the establishment of five mutant lines. Both sexes were affected in these lines. Urinary urea levels were decreased in the mutants. In addition, most mutants showed increased plasma and decreased urinary creatinine levels. Pathological investigation of kidneys from the five mutant lines revealed a broad spectrum of alterations, ranging from no macroscopic and light microscopic kidney alterations to decreased kidney weight- to- body weight ratio, dilation of the renal pelvis, and severe glomerular lesions. Thus screening for elevated plasma urea levels in a large- scale ENU mouse mutagenesis project resulted in the successful establishment of mouse strains which are valuable tools for molecular studies of mechanisms involved in urea excretion or which represent interesting models for kidney diseases.