DEVELOPMENT OF THE NATIONAL-INSTITUTES-OF-HEALTH GENETICALLY HETEROGENEOUS RAT STOCK
DEVELOPMENT OF THE NATIONAL-INSTITUTES-OF-HEALTH GENETICALLY HETEROGENEOUS RAT STOCK
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DOI：
10.1111/j.1530-0277.1984.tb05706.x
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发表时间：
1984-01-01
影响因子：
3.2
通讯作者：
SPUHLER, K
中科院分区：
文献类型：
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作者：
HANSEN, C;SPUHLER, K
METHODS的基本方案，其次是形成股票，N/Nih，是一个8路交叉的单独的近交系。选择了8个品系，因为该数量允许从可用的实验室种群中对大鼠基因库进行更多的采样。此外，根据二项式展开，使用该数量的菌株也将增加基础群体中基因型频率的分布。例如，如果只使用两个菌株，每个菌株在一个基因座上的不同等位基因是纯合的，则会产生三种不同的基因型。将菌株的数量增加到8个，每个菌株对不同的等位基因纯合，就会产生一个基因座的9种不同的基因型。将许多基因位点上的这些基因型差异相加，产生了存在于异质群体中的极大量的遗传组合。使用八个菌株需要三代才能完成育种计划。在开发这种大鼠种群的过程中，一个重要的决定是选择八个品系纳入育种计划。虽然今天可能有100多个近交系的大鼠，但许多都可以追溯到Wistar大鼠。此外，由于许多品系的起源不清楚，因此通常很难确定它们是否真的有一个独立于Wistar大鼠的起源。经过广泛的考虑，选择以下菌株作为异质性原种的祖细胞：BN/SsN、MR/N、BUF/N、M520/N、WN/N、ACI/N、WKY/N和F344/N。许多因素促成了这些特定品系的选择：它们代表了相对广泛的实验室大鼠基因组差异;至少有一些是独立起源的;最后，它们很容易获得。其中三个菌株MR/N、WN/N和WKY/N的祖先可追溯至原始Wistar种群。然而，MR/N菌株是从随后的欧洲种群发展而来的，“WKY/N来自日本种群”，WN/N来自次级美洲种群。M520/N和F344/N菌株是在20世纪20年代从经销商库存中建立的，但它们的最终来源尚不清楚。ACI/N品系是August品系和Copenhagen品系的杂交种，BN/SsN品系的起源可追溯到Wistar研究所饲养的野生大鼠种群中的一种颜色突变体。每代交配系统的实际菌株类型配对如下。第一代杂交组合包括BN/SsN × MR/N、BUF/N × M52 O/N、WN/N × ACI/N和WKY/N × F344/N。在这一代中没有共同起源的菌株杂交。产生的后代是F1动物，使得来自特定杂交的所有后代是相同的杂合子。产生Fz代的第二个交配循环如下：BN-MR X BUF-M520和WN-ACI X WKY-F344。仅进行有限数量的F1交配以产生F2代，因为每组亲本在遗传上相同。通过BN-MRBUF-M520 x WN-AC 1-WKY-F344的交配产生F1代。在这种情况下，从BN-MR-BUF-M520和从WN-AC 1-WKY-F344组中随机选择70个雌性后代和70个雄性后代进行正反交。这一特定交配对数量的选择取决于最终菌落大小的决定。管理远系繁殖种群的一个经验法则是在现有资源的情况下尽可能地产生最大的群体规模。在这种情况下，确定60对将代表可用资源和最小化在封闭殖民地情况下发生的不可避免的累积近亲繁殖之间的最佳折衷。另外10个交配被包括在内...
METHODSThe basic scheme followed in the formation of the stock, N/Nih, was an eight-way cross of separate inbred strains. Eight strains were chosen since this number allowed a greater sampling of the rat gene pool from available laboratory populations. Moreover, using this number of strains would also increase the distribution of genotypic frequencies in the base population according to the binomial expansion. For example, if only two strains, each homozygous for different alleles at one gene locus, were used, three different genotypes would be produced. Increasing the num-ber of strains to eight, each homozygous for different alleles, produces nine different genotypes for one gene locus. Summing these genotypic differences over many gene loci yields an extremely large number of genetic combinations present in the heterogeneous stock. Using eight strains required three generations to complete the breeding program. An important decision in developing this stock of rats was selecting the eight strains for inclusion in the breeding program. Although there are probably more than 100 inbred strains of rats today, many trace their origin to the Wistar Moreover, since the origin of a number of strains is obscure, it is often difficult to establish whether they, in fact, do have an origin independent of the Wistar stock. After extensive consideration, the following strains were chosen to serve as progenitors of the heterogeneous stock: BN/SsN, MR/N, BUF/N, M520/N, WN/N, ACI/N, WKY/N, and F344/N. A number of factors contributed to the choice of these particular strains: they represented a relatively broad spectrum of laboratory rat genomic differences; at least some were of independent origin; and, finally, they were readily available. Three of the strains, MR/N, WN/N, and WKY/N, trace their ancestry to the original Wistar stock. However, the MR/N strain was developed from a subsequent European stock,’the WKY/N from a Japanese stock,’and the WN/N from a secondary American stock. The M520/N and F344/N strains were established in the 1920s from dealer stocks, but their ultimate origin is unknown. The ACI/N strain resulted from a hybrid between the August and Copenhagen strains, and the BN/SsN strain traces its origin to a color mutant in a stock of wild rats maintained at the Wistar In~ titute.~.‘The actual pairing of strain types for the mating system in each generation were as follows. The first generation of matings consisted of BN/SsN x MR/N, BUF/N x M52O/N, WN/N x ACI/N, and WKY/N x F344/N. No strains of common origin were crossed in this generation. The offspring produced were F, animals such that all progeny from a particular cross were identical heterozygotes. The second cycle of matings to produce the Fz generation was as follows: BN-MR X BUF-M520 and WN-ACI x WKY-F344. Only a limited number of F, mating was made to produce the F2 generation, since each set of parents was genetically identical. The F, generation was produced by the mating of BN-MRBUF-M520 x WN-ACl-WKY-F344. In this case, 70 female and 70 male progeny were chosen at random from the BN-MR-BUF-M52O and from the WN-ACl-WKY-F344 groups to make reciprocal crosses. The choice of this particular number of mating pairs was predicated on the decision as to the final colony size. A rule of thumb for managing outbred stocks is to produce the largest colony size possible consistent with available resources. In this case, it was determined that 60 pairs would represent the best compromise between available resources and minimizing the inevitable cumulative inbreeding that occurs in a closedcolony situation. The additional 10 mating were included to …