Novel phenotypes identified by plasma biochemical screening in the mouse
Novel phenotypes identified by plasma biochemical screening in the mouse
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DOI：
10.1007/s00335-002-2188-1
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发表时间：
2002-10-01
期刊：
影响因子：
2.5
通讯作者：
Hunter, AJ
中科院分区：
文献类型：
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作者：
Hough, TA;Nolan, PM;Hunter, AJ
我们在小鼠中使用ENU诱变快速产生新的突变表型，用于基因功能研究和作为人类疾病的新动物模型（Nolan et al. 2000b）。该项目的一个重点是开发血液生化筛查。在8-12周龄时，从ENU诱变的雄性小鼠F-1子代中采集了约300多份血液。这产生了大约125摩尔的血浆，用于在奥林巴斯分析仪上执行17个标准生化测试的剖面。F，小鼠的队列也老化，然后重新测试以检测晚发表型。总共筛选了1961例F(1)例。通过运行均值和标准差确定异常值。70只小鼠血浆生化一致异常，29只进入遗传检测。其中，9种表型被证实是遗传的，10种被发现不是遗传的，10种仍在测试中。遗传突变表型包括异常脂质谱（低总胆固醇和高密度脂蛋白胆固醇，高甘油三酯）；骨和肝脏代谢异常（低ALP、高ALP、高ALT和AST）；血浆电解质水平异常（高钠、高氯）；以及对糖尿病（高葡萄糖）研究感兴趣的表型。携带突变的基因位点目前正在绘制和进一步表征。我们的结果验证了我们的生化筛选，这适用于其他诱变项目，我们已经产生了一组新的突变体，具有明确的代谢表型。
We used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for both gene function studies and use as new animal models of human disease (Nolan et al. 2000b). One focus of the program was the development of a blood biochemistry screen. At 8-12 weeks of age, approximately 300 mul of blood was collected from F-1 offspring of ENU mutagenized male mice. This yielded approximately 125 mul of plasma, used to perform a profile of 17 standard biochemical tests on an Olympus analyzer. Cohorts of F, mice were also aged and then retested to detect late onset phenotypes. In total, 1,961 F(1)s were screened. Outliers were identified by running means and standard deviations. Of 70 mice showing consistent abnormalities in plasma biochemistry, 29 were entered into inheritance testing. Of these, 9 phenotypes were confirmed as inherited, 10 found not to be inherited, and 10 are still being tested. Inherited mutant phenotypes include abnormal lipid profiles (low total and HDL cholesterol, high triglycerides); abnormalities in bone and liver metabolism (low ALP, high ALP, high ALT, and AST); abnormal plasma electrolyte levels (high sodium and chloride); as well as phenotypes of interest for the study of diabetes (high glucose). The gene loci bearing the mutations are currently being mapped and further characterized. Our results have validated our biochemical screen, which is applicable to other mutagenesis projects, and we have produced a new set of mutants with defined metabolic phenotypes.