Yoshiki Atsushi, Moriwaki Kazuo
Experimental Animal Division, Department of Biological Systems, RIKEN BioResource Center.
ILAR J. 2006;47(2):94-102. doi: 10.1093/ilar.47.2.94.
Now that sequencing of the mouse genome has been completed, the function of each gene remains to be elucidated through phenotypic analysis. The "genetic background" (in which each gene functions) is defined as the genotype of all other related genes that may interact with the gene of interest, and therefore potentially influences the specific phenotype. To understand the nature and importance of genetic background on phenotypic expression of specific genes, it is necessary to know the origin and evolutionary history of the laboratory mouse genome. Molecular analysis has indicated that the fancy mice of Japan and Europe contributed significantly to the origin of today's laboratory mice. The genetic background of present-day laboratory mice varies by mouse strain, but is mainly derived from the European domesticus subspecies group and to a lesser degree from Asian mice, probably Japanese fancy mice, which belong to the musculus subspecies group. Inbred laboratory mouse strains are genetically uniform due to extensive inbreeding, and they have greatly contributed to the genetic analysis of many Mendelian traits. Meanwhile, for a variety of practical reasons, many transgenic and targeted mutant mice have been created in mice of mixed genetic backgrounds to elucidate the function of the genes, although efforts have been made to create inbred transgenic mice and targeted mutant mice with coisogenic embryonic stem cell lines. Inbred mouse strains have provided uniform genetic background for accurate evaluation of specific genes phenotypes, thus eliminating the phenotypic variations caused by mixed genetic backgrounds. However, the process of inbreeding and selection of various inbred strain characteristics has resulted in inadvertent selection of other undesirable genetic characteristics and mutations that may influence the genotype and preclude effective phenotypic analysis. Because many of the common inbred mouse stains have been established from relatively small gene pools, common inbred strains have limitations in their genetic polymorphisms and phenotypic variations. Wild-derived mouse strains can complement deficiencies of common inbred mouse strains, providing novel allelic variants and phenotypes. Although wild-derived strains are not as tame as the common laboratory strains, their genetic characteristics are attractive for the future study of gene function.
既然小鼠基因组测序已经完成，每个基因的功能仍有待通过表型分析来阐明。“遗传背景”（每个基因在其中发挥作用）被定义为所有其他可能与感兴趣基因相互作用的相关基因的基因型，因此可能会影响特定表型。为了理解遗传背景对特定基因表型表达的性质和重要性，有必要了解实验室小鼠基因组的起源和进化历史。分子分析表明，日本和欧洲的观赏小鼠对当今实验室小鼠的起源有重大贡献。当今实验室小鼠的遗传背景因小鼠品系而异，但主要源自欧洲小家鼠亚种组，在较小程度上源自亚洲小鼠，可能是属于小家鼠亚种组的日本观赏小鼠。近交系实验室小鼠品系由于广泛的近亲繁殖而在基因上是一致的，它们对许多孟德尔性状的遗传分析做出了巨大贡献。同时，出于各种实际原因，已经在混合遗传背景的小鼠中创建了许多转基因和靶向突变小鼠以阐明基因的功能，尽管人们已努力用同基因胚胎干细胞系创建近交转基因小鼠和靶向突变小鼠。近交小鼠品系为准确评估特定基因表型提供了一致的遗传背景，从而消除了由混合遗传背景引起的表型变异。然而，近亲繁殖和选择各种近交系特征导致无意中选择了其他不良遗传特征和突变，这些可能会影响基因型并妨碍有效的表型分析。由于许多常见的近交小鼠品系是从相对较小的基因库中建立的，常见近交品系在遗传多态性和表型变异方面存在局限性。野生来源的小鼠品系可以弥补常见近交小鼠品系的不足，提供新的等位基因变体和表型。虽然野生来源的品系不像常见的实验室品系那样温顺，但它们的遗传特征对未来的基因功能研究具有吸引力。
