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Establishment of Mouse Consomic Lines

小鼠体系的建立

基本信息

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

项目摘要

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.

根据定义，当两个品系的小鼠相差一个完整的染色体对时，它们被称为同源的。鉴于小鼠具有21条不同染色体的核型（19条常染色体+ X，Y染色体），需要21个同源体小鼠品系才能被供体品系完全覆盖小鼠染色体，其中一条完整染色体被引入称为受体的共同遗传背景中。染色体替换是通过将被鉴定为与所选染色体杂合的个体与受体品系进行六至七次回交来实现的。许多病理状况和疾病如癌症和糖尿病都是在多基因控制下的。当涉及大量基因且基因间存在上位性相互作用时，它们通常难以分析。在这些情况下，如果感兴趣的表型在同源体菌株中似乎偏离遗传背景菌株中已知的表型，则其遗传控制必须与所关注的染色体置换相关。进一步的遗传分析将大大简化。MSM品系，其来源于日本野生小鼠Mus musculus molossinus，作为供体品系，C57 BL/6 J实验室品系作为受体。这两种菌株在遗传上彼此非常遥远，因此它们在许多遗传性状上不同。这种遗传差异有助于任何待检测表型的染色体分配，并且在基于DNA标记多态性的连锁分析中非常有用。我们使用微卫星DNA标记，每条染色体至少5个标记，在回交的每一步中选择个体。结果在C57 BL/6 J株的遗传背景下，获得了15个携带MSM衍生染色体的同源株。