Validation studies with Muta™ mouse: A transgenic mouse model for detecting mutations in vivo

Validation studies with Muta™ mouse: A transgenic mouse model for detecting mutations in vivo
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Muta™ 小鼠验证研究:用于检测体内突变的转基因小鼠模型

DOI:
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发表时间:
1991
影响因子:
2.8
通讯作者:
B. Myhr
B. Myhr
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
B. Myhr

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MutaMouse是一种转基因小鼠,可以通过简单的实验室方法检测体内任何组织中的突变。目标是通过lambda噬菌体将细菌lacZ基因整合到每个小鼠细胞的基因组中,从而在同源对的两条染色体的单个位点上存在约40个拷贝的连接体。为了评估MutaMouse在检测体内诱变方面的潜在用途,我们将几种已知的诱变剂/致癌物应用于8-10周龄的雄性动物。研究了N -乙基- N -亚硝基脲(ENU)、氯苯、丙卡嗪、环磷酰胺和丙烯酰胺在骨髓、肝脏和睾丸中的致突变作用(每日1次或5次)。此外,皮肤涂漆研究(单次应用)用二甲基苯并蒽(DMBA)、N‐甲基‐N′‐硝基‐N‐亚硝基胍(MNNG)和乙酸进行。突变频率的增加明显是由所有八种化学物质引起的,其幅度取决于化学物质、剂量、给药方法、分析的组织以及处理和分离DNA之间的时间间隔。相对于所分析的lacZ基因群体和每个治疗组的动物数量,呈现了突变频率的变异性数据。讨论了MutaMouse模型在遗传突变检测中的应用。
MutaMouse is a transgenic mouse engineered to detect mutations in vivo in any tissue of choice by using simple laboratory methods. The target is a bacterial lacZ gene incorporated via lambda phage into the genome of each mouse cell such that a concatamer of approximately 40 copies exists at a single site on both chromosomes of a homologous pair. In order to assess the potential usefulness of MutaMouse in detecting in vivo mutagenesis, several known mutagens/carcinogens were applied to male animals of 8–10 weeks in age. Intraperitoneal injections (single or 5 daily doses) of N‐ethyl‐N‐nitrosourea (ENU), chlorambucil, procarbazine, cyclophosphamide, and acrylamide were investigated for mutagenic effects in bone marrow, liver, and testes. In addition, skin painting studies (single application) were performed with dimethylbenzanthracene (DMBA), N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), and acetic acid. Increases in mutant frequency were clearly induced by all eight chemicals, the magnitudes of which were dependent on the chemical, dose, method of dosing, tissue analyzed, and the time lapse between treatment and isolation of DNA. Data on variability in mutant frequency was presented relative to the analyzed population of lacZ genes and number of animals per treatment group. Application of the MutaMouse model to the detection of heritable mutations was discussed.
丙烯酰胺单体诱导小鼠雄性生殖细胞中的特异性位点突变。
DOI: 10.1016/0165-7992(91)90114-j
发表时间: 1991
期刊: Mutation research
影响因子: --
作者:
Russell,LB;Hunsicker,PR;Cacheiro,NL;Generoso,WM
通讯作者: Generoso,WM
Chlorambucil 可有效诱导小鼠生殖细胞缺失突变。
DOI: 10.1073/pnas.86.10.3704
发表时间: 1989
影响因子: 11.1
作者:
Russell,LB;Hunsicker,PR;Cacheiro,NL;Bangham,JW;Russell,WL;Shelby,MD
通讯作者: Shelby,MD