Evolutionary status of the genetic background in the wild mice and its participation in manifestation of the genes for biological functions in mouse models

(1)三个小鼠亚种群遗传分化的估计：我们已经从遗传学的角度论证了小家鼠可能分化为家鼠、castaneus和肌肉亚种三个小鼠亚种群，它们之间的相互间隔大约有100万年。对这些亚种群中1000个微卫星DNA位点的基因扫描分析证实了上述可能性。8个野生衍生菌株的22个基因位点的核苷酸序列比较也显示出相似的分组。利用FISH技术进行细胞遗传学调查，在东北亚人群中观察到5种主要卫星dna的染色体分布模式。这些是肌肉型、gansuensis型、molossinus型、肌肉+molossinus型和肌肉+castaneus型。在北海道，东部种群线粒体DNA为肌群型，中部种群线粒体DNA为castaneus型。然而，在我们调查的人群中，Y染色体上的Sry基因几乎是肌肉型的。(2)局部人群遗传多态性：对血红蛋白基因d-、p-和w1单倍型b1和b2的核苷酸序列分析表明，p单倍型是d单倍型b1和w1单倍型b2的重组体。内含子核苷酸序列表明，d-和w1单倍型可能的分化发生在大约200万年前，d-和w1单倍型的重组发生在大约20万年前。在哈萨克斯坦人群中，发现了一种新的Hbb单倍型w2。核苷酸序列数据表明，该基因为重组蛋白，携带w1单倍型b1和d单倍型b2。在这个地区，也发现了一种转移变异。在castaneus属Mysole群体中观察到肽酶-3缺失突变体，并将其固定为MYS/Mz自交系。研究强烈提示，氨基甲酸乙酯诱导的肺肿瘤遗传易感性的显性抑制可能只存在于castaneus亚种组中。(3)进化遥远遗传背景对基因表现的影响：Rim4突变基因在实验室小鼠品系C57BL遗传背景中表现出明显的多指表型，而在日本野生衍生的MSM品系中完全没有表现出来。第二个调控基因在2号染色体1附近被检测到。经鉴定，该突变的致病基因为一种核糖体蛋白Rp138。同样在这种情况下，msm衍生的Rp138抑制了短尾表型。少

(1) Estimation of the genetic differentiation of three mouse subspecies groups :We have already demonstrated the possible differentiation of Mus musculus species into three mouse subspecies groups, domesticus-, castaneus- and musculus subspecies group from genetic view point, each of which was mutually separated by roughly one million years. The gene scan analysis of 1000 microsatellite DNA loci in these subspecies groups approved the above possibility. Comparison of the nucleotide sequences in 22 gene loci among 8 wild derived strains also showed the similar grouping. In cytogenetical survey using FISH technique, five types in the chromosomal distribution pattern of major satellite DNAs were observed in northeast Asian populations. These are musculus-, gansuensis-, molossinus-, musculus+molossinus- and musculus+castaneus type.In Hokkaido, mitochondoria DNA was musculus group type in the eastern populations and castaneus group type in the central populations. But Sry gene on Y chromoso … More me, however, was almost musculus type in the populations we surveyed.(2) Genetic polymorphism in local populations :The nucleotide sequence analyses of d-, p- and w1 haplotype hemoglobin genes , b1 and b2, demonstrated that p haplotype was a recombinant having d haplotype b1 and w1 haplotype b2. Intron nucleotide sequences suggested that the possible differentiation of d- and w1 haplotype occurred around 2 million years ago and the recombination between d- and w1 haplotype around 200 thousands years ago. In a Kazakstan population, a new Hbb haplotype w2 was found. The nucleotide sequence data suggested that it was a recombinant carrying w1 haplotype b1 and d haplotye b2. In this area, a transferring variant was found out as well. In a Mysole population belonging to castaneus group, peptidase-3 delition mutant was observed and fixed as MYS/Mz inbred strain. The possibility that a dominant suppression in the genetic susceptibility to urethane induced lung tumor was present only in the castaneus subspecies group, was strongly suggested.(3) Effect of evolutionarily remote genetic background on gene manifestation :Rim4 mutant gene exhibited the clear polydactylous phenotype in the genetic background of laboratory mouse strain C57BL, while it completely failed to show it in the Japanese wild derived MSM strain. The second regulatory gene was detected near Ist on the chromosome 2. Causative genetic element for Tail-short mutation was identified as Rp138, a ribosome protein. Again in this case, MSM-derived Rp138 suppressed the Tail-short phnotype. Less