Phelan J P
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138.
Exp Gerontol. 1992;27(2):147-59. doi: 10.1016/0531-5565(92)90039-3.
Inbred strains, outbred strains, and natural populations of rodents differ greatly in the amount and nature of the genetic variability they possess. Consequently, as models of human aging they vary with respect to the areas of research to which they are best suited. Inbred strains, in which all individuals are genetically identical, are best suited as models of specific disease processes and for manipulations involving tissue transplantation. Their lack of genetic variability, however, and the disruption of genetic linkage groups that occurs during inbreeding limit their value as models of more general aging processes. Outbred strains exhibit large interindividual genetic variation--a result of ongoing random accumulation of deleterious alleles with late ages of action. This makes them ideal models for studying the diversity of pathologic lesions, connections between pathologies, and susceptibility to pathologic lesions that collectively produce the reductions in reproductive capacity, physiological efficiency, and viability that are characteristic of aging. Natural populations also may exhibit relatively large amounts of interindividual genetic variability. However, difficulties with husbandry, variable parasite loads, and complex population genetics can compromise their suitability as models of human aging. Ultimately, a consideration of the range of animal models available and a more careful matching of the goals of a study with the genetic system of the model will prove fruitful to gerontology.
近交系、远交系和啮齿动物自然种群在其拥有的遗传变异性的数量和性质上有很大差异。因此，作为人类衰老模型，它们在最适合的研究领域方面存在差异。近交系中所有个体基因相同，最适合作为特定疾病过程的模型以及用于涉及组织移植的操作。然而，它们缺乏遗传变异性，以及在近亲繁殖过程中发生的基因连锁群的破坏，限制了它们作为更一般衰老过程模型的价值。远交系表现出较大的个体间遗传变异——这是有害等位基因在晚期持续随机积累的结果。这使它们成为研究病理损伤的多样性、病理之间的联系以及对病理损伤的易感性的理想模型，这些共同导致了衰老所特有的生殖能力、生理效率和生存能力的降低。自然种群也可能表现出相对大量的个体间遗传变异。然而，饲养困难、寄生虫负荷可变以及复杂的群体遗传学可能会影响它们作为人类衰老模型的适用性。最终，考虑可用动物模型的范围，并使研究目标与模型的遗传系统更仔细地匹配，将对老年学产生丰硕成果。
