Establishment of Mouse Consomic Lines

小鼠体系的建立

• 批准号: 07558116
• 负责人: SHIROISHI Toshihiko
• 金额: $ 11.52万
• 依托单位: National Institute of Genetics
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07558116/
• 关键词: mouse; subspecies; chromosome; backcross; microsatellite; consomic; linkage; 遺伝的多型; マイクロサテライトマーカー

From the definition, two strains of mouse are referred to as consomic when they differ by one complete chromosome pair. Given that mouse has a karyotype with 21 different chromosomes (19 autosomes + X,Y chromosomes), 21 consomic mouse strains are required for full coverage of mouse chromosomes by donor strains, from which one complate chromosome is introduced into the common genetic background referred to as recipient. Chromosome substitution is achieved by six to seven times backcrossing of individuals identified as heterozygous for the selected chromosome to the recipient strain.It has been well established that many pathological conditions and diseases like cancer and diabetes are under multigenic control. They are generally difficult to analyze when a great number of genes are involved and epistatic interactions are present among the genes. In these cases, if a phenotype of interest appears to deviate in a consomic strain from what is known in the genetic background strain, its genetic control must be related to chromosomal substitution to be concerned. Further genetic analysis will then be considerably simplified.We started to establish consomic strains, using. MSM strain, which is derived from Japanese wild mouse, Mus musculus molossinus, as donor strain and a C57BL/6J laboratory strain as recipient. These two strains are genetically very remote from each other so that they differ in a number of genetic traits. This genetic defference faclitates in chromosomal assignment of any phenotype to be examined and is of great use in linkage analysis based on polymorphism of DNA markers. We used microsatellite DNA markers, at least five markers per chromosome, for selection of individuals in each step of backcrossing. As a result, we have obtained 15 consomic strains which carry MSM derived chromosomes in the genetic background of C57BL/6J strain.

从定义来看，当小鼠通过一个完整的染色体对时，将两种鼠标称为综合。鉴于小鼠的核型具有21种不同的染色体（19个常染色体 + X，Y染色体），因此需要21种构造小鼠菌株才能通过供体菌株对小鼠染色体的全部覆盖，从中将一个共反射的染色体引入常见的遗传背景中。染色体的取代是通过六到七倍的六倍的反向交叉，对被选定的染色体鉴定为受体菌株的杂合子的个体。当涉及大量基因并且基因之间存在上皮相互作用时，它们通常很难分析。在这些情况下，如果感兴趣的表型似乎偏离了遗传背景菌株中已知的遗传控制，则其遗传控制必须与染色体替代有关。然后，将大大简化进一步的遗传分析。我们开始使用合成菌株。 MSM菌株是由日本野生小鼠Mus Musculus molossinus衍生而来的，作为供体菌株和C57BL/6J实验室菌株作为受体。这两种菌株在遗传上彼此之间非常遥远，因此它们在许多遗传特征上有所不同。这种遗传脱卵在任何要检查的表型的染色体分配中表现出色，并且基于DNA标记的多态性，在链接分析中非常有用。我们在每个反向交叉的步骤中选择了每个染色体的微卫星DNA标记，每染色体至少五个标记。结果，我们获得了15种伴侣菌株，这些菌株在C57BL/6J菌株的遗传背景中携带MSM衍生的染色体。

项目成果

Shiroishi, T., Ueda, Y., Ball, S., Nagamine, C.M., Sagai, T and Moriwaki, K.: "Genetic differentiation of mouse Y chromosome." J.Repro. Dev.43, Supplement. 17-18 (1997)

Shiroishi, T.、Ueda, Y.、Ball, S.、Nagamine, C.M.、Sagai, T 和 Moriwaki, K.：“小鼠 Y 染色体的遗传分化”。

Tanooka,H.: "Distribution of the p53 psudogene amog mouse species and subspecies" Mammalian Genome. 6. 360-362 (1995)

Tanooka,H.：“p53 psudogene amog 小鼠物种和亚种的分布”哺乳动物基因组。

Koide,T: "A new inbred strain JF1 established from Japanese fancy mouse carrying the classical piebald allele." Mammal. Genome. 9. 15-19 (1998)

Koide,T：“从携带经典花斑等位基因的日本花式小鼠中建立的新近交系 JF1。”

Masuya,H.: "A duplicated zone of polarizing activity(ZPA)in polydactylous mouse mutants" Genes & Development. 9. 1645-1653 (1995)

Masuya,H.：“多指小鼠突变体中的重复极化活性区（ZPA）”基因

Nagao, Y.Totsuka, Y., Atomi, Y., Kaneda, H., Fischer Lindahl, K.and Yonekawa, H.: "Decreased physical performance of congenic mice with mismatch between the nuclear and the mirochondrial genome." Genes and Genetic Systems. (in press).

Nagao, Y.Totsuka, Y.、Atomi, Y.、Kaneda, H.、Fischer Lindahl, K. 和 Yonekawa, H.：“核基因组和线粒体基因组不匹配导致同源小鼠的身体性能下降。”