Spontaneous mutation in Big Blue® mice from fetus to old age:: tissue-specific time courses of mutation frequency but similar mutation types
Spontaneous mutation in Big Blue® mice from fetus to old age:: tissue-specific time courses of mutation frequency but similar mutation types
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DOI：
10.1002/em.20004
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发表时间：
2004-01-01
影响因子：
2.8
通讯作者：
Sommer, SS
中科院分区：
文献类型：
--
作者：
Hill, KA;Buettner, VL;Sommer, SS
转基因小鼠突变检测系统可以快速确定突变的频率和类型，从而直接检查衰老、神经变性和癌症的突变标记。Big Blue(R)转基因小鼠突变检测系统用于确定多种组织类型中自发突变的频率和性质与年龄的关系。从交配后13.5天的全胎和出生后10天、3、10和25个月龄的大蓝转基因小鼠的6个组织(小脑、前脑、胸腺、肝脏、脂肪组织和雄性生殖系)中提取核DNA。共筛选出4000万个斑块形成单位(PFU)。突变频率随年龄增长的时间进程具有明显不同的形态。在不同组织中(P<；10(-6))。到13.5DPC时，整个胎儿的突变频率已经开始增加，从受孕时的理论零值增加到大约是成年中期(3-10个月)平均值的一半。从第10天到3月，肝脏突变频率显著增加(P=0.007)，小脑、前脑和胸腺突变频率呈增加趋势。从3个月到10个月，被检查的任何组织的突变频率都没有显著变化。从10到25个月，肝(P<；10(-6))和脂肪组织(P=0.002)的突变频率显著增加，而在其他组织(小脑、前脑和男性生殖系)中突变频率没有明显增加。有趣的是，男性生殖系的突变频率一直是最低的，在老年基本保持不变。突变类型的频谱不随年龄、组织类型和性别而改变，尽管如先前报道的那样，串联GG-->；TT突变是组织特有的，并显示出随着年龄和某些热点的显著增加(Buettner VL等人)。[1999]：Environ Mal诱变剂33：320-324；Hill Ka等人。[2003年]：Mutat Res534：173186)。所有组织类型的突变类型谱大体上是相同的，尽管随着年龄的增长，特定组织的突变频率增加。这些数据为今后内源和外源诱变的研究提供了有益的参考。(C)2002年Wiley-Liss，Inc.
Transgenic mouse mutation detection systems permit rapid determination of the frequency and type of mutations allowing direct examination of mutational markers for aging, neurodegeneration, and cancer. The Big Blue(R) transgenic mouse mutation detection system was used to determine the frequency and nature of spontaneous mutations versus age in multiple tissue types. Nuclear DNA was extracted from whole fetus at 13.5 days postcoitus (dpc) and from six tissues postbirth (cerebellum, forebrain, thymus, liver, adipose tissue, and male germline) of Big Blue transgenic mice at four ages: 10 days and at 3, 10, and 25 months postbirth. Forty million total plaque-forming units (pfu) were screened. The time course of mutation frequency with age had a significantly different shape. in different tissues (P < 10(-6)). By 13.5 dpc, the whole fetus mutation frequency had already started increasing from the theoretical zero at conception to a value that was about one-half the mid-adulthood (3-10 months) average. From 10 days to 3 months, mutation frequency increased significantly in liver (P = 0.007) and showed an increasing trend in cerebellum, forebrain, and thymus. From 3 to 10 months, there was no significant change in mutation frequency in any tissue examined. From 10 to 25 months, the mutation frequency increased significantly in liver (P < 10(-6)) and adipose tissue (P = 0.002), but not in the other tissues examined (cerebellum, forebrain, and male germline). It is of interest that the mutation frequency in the male germline is consistently the lowest, remaining essentially unchanged in old age. The spectrum of mutation types was unaltered with age, tissue type and gender, although, as previously reported, tandem GG-->TT mutations are tissue specific and show significant increases with age and certain hotspots (Buettner VL et al. [1999]: Environ Mal Mutagen 33: 320-324; Hill KA et al. [2003]: Mutat Res 534:173186). The spectrum of mutation types was generally the same for all tissue types, despite the tissue-specific increases in mutation frequency with age. These data provide a useful reference for future studies of endogenous and exogenous mutagenesis. (C) 2002 Wiley-Liss, Inc.