Intersubspecific subcongenic mouse strain analysis reveals closely linked QTLs with opposite effects on body weight
Intersubspecific subcongenic mouse strain analysis reveals closely linked QTLs with opposite effects on body weight
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DOI：
10.1007/s00335-011-9323-9
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发表时间：
2011-06-01
期刊：
影响因子：
2.5
通讯作者：
Ishikawa, Akira
中科院分区：
文献类型：
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作者：
Mollah, Md. Bazlur R.;Ishikawa, Akira
先前的全基因组QTL研究揭示了许多影响出生后体重和生长的QTL在亚种间回交小鼠群体之间的C57BL/6J（B6）品系和野生小家鼠栗小鼠捕获在菲律宾。随后，在B6与B6杂交的F-2代群体中发现了几个与体成分性状紧密连锁的QTL。Cg-Pbwg1是B6遗传背景下的一个同源株系，其近端第2染色体上携带有生长QTL Pbwg1。然而，没有影响体重的QTL已在F2群体中重复，除了定位一个超显性QTL，导致体重的杂种优势。本研究从B6. Cg-Pbwg 1同源系中分离出17个栗叶重叠和非重叠的亚种间亚同源系，以寻找影响体重的QTL，并将其遗传分离到不同的紧密连锁位点。与B6株系的表型比较表明，两个紧密连锁但不同的QTL，控制体重，命名为Pbwg1.11和Pbwg1.12，分别位于8.9-Mb区域之间的D2Mit270和D2Mit472和下一个3.6-Mb区域之间的D2Mit205和D2Mit182。进一步的分析，使用F2分离群体之间的B6和两个选定的亚同源株系的每一个的互交证实了这两个体重QTL的存在。Pbwg1.11对6、10、13周龄的体重具有累加效应，其Castaneus等位基因降低了体重，而Pbwg1.12的Castaneus等位基因以显性方式作用，尽管野生型Castaneus小鼠的体重是B6小鼠的60%，但其在6、10、13周龄的体重令人惊讶地增加。这些发现说明了复杂的遗传性质的体重调节和支持的重要性，亚同源小鼠分析解剖密切相关的基因座。
A previous genome-wide QTL study revealed many QTLs affecting postnatal body weight and growth in an intersubspecific backcross mouse population between the C57BL/6J (B6) strain and wild Mus musculus castaneus mice captured in the Philippines. Subsequently, several closely linked QTLs for body composition traits were revealed in an F-2 intercross population between B6 and B6.Cg-Pbwg1, a congenic strain on the B6 genetic background carrying the growth QTL Pbwg1 on proximal chromosome 2. However, no QTL affecting body weight has been duplicated in the F2 population, except for mapping an overdominant QTL that causes heterosis of body weight. In this study, we developed 17 intersubspecific subcongenic strains with overlapping and nonoverlapping castaneus regions from the B6.Cg-Pbwg1 congenic strain in order to search for and genetically dissect QTLs affecting body weight into distinct closely linked loci. Phenotypic comparisons of several developed subcongenic strains with the B6 strain revealed that two closely linked but distinct QTLs that regulate body weight, named Pbwg1.11 and Pbwg1.12, are located on an 8.9-Mb region between D2Mit270 and D2Mit472 and on the next 3.6-Mb region between D2Mit205 and D2Mit182, respectively. Further analyses using F2 segregating populations obtained from intercrosses between B6 and each of the two selected subcongenic strains confirmed the presence of these two body weight QTLs. Pbwg1.11 had an additive effect on body weight at 6, 10, and 13 weeks of age, and its castaneus allele decreased it. In contrast, the castaneus allele at Pbwg1.12 acted in a dominant fashion and surprisingly increased body weight at 6, 10, and 13 weeks of age despite the body weight of wild castaneus mice being 60% of that of B6 mice. These findings illustrate the complex genetic nature of body weight regulation and support the importance of subcongenic mouse analysis to dissect closely linked loci.