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

野生小鼠遗传背景的进化状况及其参与小鼠模型生物功能基因的表现

• 批准号: 10480234
• 负责人: MORIWAKI Kazuo
• 金额: $ 7.55万
• 依托单位: The Graduate University for Advanced Studies
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10480234/
• 关键词: Wild mouse; Mitochondrial DNA; Hemoglobin variants; Genetic background; Modifier gene; Subspecies group; Microsatellite DNA; FISH analysis; マウス亜種グループ; ヘモグロビン; 骨格形成遺伝子; リボソーム蛋白遺伝子; 日本産野生マウス; ヘモグロビン・ベータ・w1; DNA塩基配列; サテライトDNA; FISH; チトクロームb

(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

(1)三个小鼠亚种群遗传分化的估计：我们已经从遗传角度证明了小家鼠物种可能分化为三个小鼠亚种群：家鼠亚种群、栗亚种群和小家鼠亚种群，每个亚种群彼此相隔大约一百万年。对这些亚种群1000个微卫星DNA位点的基因扫描分析证实了上述可能性。对8个野生菌株的22个基因位点的核苷酸序列进行比较也显示出相似的分组。在使用FISH技术的细胞遗传学调查中，在东北亚人群中观察到主要卫星DNA的染色体分布模式有五种类型。这些是musculus-、gansuensis-、molossinus-、musculus+molossinus-和musculus+castaneus类型。在北海道，东部人群的线粒体DNA是musculus组类型，中部人群是castaneus组类型。而Y染色体上的Sry基因在我们调查的人群中几乎是肌肉型。(2)当地人群遗传多态性：对d、p、w1单倍型血红蛋白基因b1、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单倍型之间的重组发生在大约20万年前。在哈萨克斯坦人群中，发现了新的 Hbb 单倍型 w2。核苷酸序列数据表明它是携带w1单倍型b1和d单倍型b2的重组体。在这一领域，还发现了一种转移变体。在属于栗组的 Mysole 群体中，观察到 peptidase-3 delition 突变体并将其固定为 MYS/Mz 近交系。强烈建议对乌拉坦诱导的肺肿瘤遗传易感性的显性抑制仅存在于栗亚种组中。(3)进化上遥远的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的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这种表型。第二个调控基因在 2 号染色体上的 Ist 附近检测到。Tail-short 突变的致病遗传元件被确定为 Rp138（一种核糖体蛋白）。同样在这种情况下，MSM 衍生的 Rp138 抑制了尾部短表型。较少的

项目成果

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