Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse.
Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse.
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苯丁酸氮芥诱导的小鼠种系突变的遗传和分子分析。
DOI：
10.1073/pnas.87.4.1416
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发表时间：
1990
影响因子：
11.1
通讯作者：
Liane B. Russell
中科院分区：
文献类型：
--
作者：
E. Rinchik;J. Bangham;P. Hunsicker;Nestor L A Cacheiro;B. Kwon;Ian J. Jackson;Liane B. Russell
从涉及诱变剂苯丁酸氮芥的特定位点突变率实验中回收的十八个变体进行了多次遗传和分子分析。大多数突变被发现是纯合致死的。由于致死率通常是多位点缺失事件的推定证据，因此通过 Southern 印迹分析，使用位于或与几个特定位点测试标记紧密相连的探针，即白化 (c)、棕色 (b) 和稀释 (d) 来分析 10 个突变。精原细胞后生殖细胞中出现的所有八个突变（两个 c；三个 b；两个 d；和一个稀短耳 [Df(d se)]）的 DNA 序列均被删除。对于干细胞精原细胞中出现的剩余两个 d 突变，没有获得删除两个 d-se 区域探针的证据。六个初级突变体也产生低产仔数（“半不育”）。迄今为止，核型分析已证实这六个基因中的四个存在相互易位。苯丁酸氮芥在精原细胞后阶段诱导的突变中的高频率缺失和易位，加上苯丁酸氮芥在这些阶段诱导突变的总体高效率，应该使苯丁酸氮芥诱变可用于在整个小鼠基因组中产生具有实验价值的种系缺失。
Eighteen variants recovered from specific locus mutation rate experiments involving the mutagen chlorambucil were subjected to several genetic and molecular analyses. Most mutations were found to be homozygous lethal. Because lethality is often presumptive evidence for multilocus-deletion events, 10 mutations were analyzed by Southern blot analysis with probes at, or closely linked to, several of the specific locus test markers, namely, albino (c), brown (b), and dilute (d). All eight mutations (two c; three b; two d; and one dilute-short ear [Df(d se)]) that arose in post-spermatogonial germ cells were deleted for DNA sequences. No evidence for deletion of two d-se region probes was obtained for the remaining two d mutations that arose in stem-cell spermatogonia. Six of the primary mutants also produced low litter sizes ("semisterility"). Karyotypic analysis has, to date, confirmed the presence of reciprocal translocations in four of the six. The high frequency of deletions and translocations among the mutations induced in post-spermatogonial stages by chlorambucil, combined with its overall high efficiency in inducing mutations in these stages, should make chlorambucil mutagenesis useful for generating experimentally valuable germ-line deletions throughout the mouse genome.