A growth QTL (Pbwg1) region of mouse chromosome 2 contains closely linked loci affecting growth and body composition
A growth QTL (Pbwg1) region of mouse chromosome 2 contains closely linked loci affecting growth and body composition
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DOI：
10.1007/s00335-007-9009-5
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发表时间：
2007-04-01
期刊：
影响因子：
2.5
通讯作者：
Namikawa, Takao
中科院分区：
文献类型：
--
作者：
Ishikawa, Akira;Kim, Eun-Hee;Namikawa, Takao
以往的QTL研究已经在C57BL/6J和野生卡氏小鼠之间的亚种间回交小鼠群体中发现了24个控制出生后3-10周体重和生长的QTL，后者的体型是C57BL/6J的60%。位于近端2号染色体上最有效的QTL(Pbwg1)上的卡萨尼乌斯等位基因阻碍了生长。在这项研究中，我们通过与C57BL/6J的轮回杂交，培育出了一个含有Pbwg1上的Castaneus等位基因的44.1-Mb间隔的同源菌株。同系小鼠在1~3周龄体重增加显著高于C57BL/6J，10周龄白色脂肪垫重量显著低于C57BL/6J。但同源品系与C57BL/6J品系在1-10周龄体重无明显差异。对这两个品系之间的269只F-2小鼠进行的QTL分析没有发现任何影响1、3、6和10周龄体重的QTL，但在Pbwg1区域内发现了8个紧密连锁的QTL，这些QTL影响1-3周龄的体重增加、瘦体重、白色脂肪垫重量和体长。在所有脂肪垫QTL上的蓖麻子等位基因降低了表型，而在其余的生长和体成分QTL上，它们增加了性状值。这些结果表明，Pbwg1最初似乎是一个单一的基因座，但被分解成几个对总体体重组成性状有相反影响的基因座。这给出了在原始回交群体中发现的Pbwg1效应丧失的原因。
Previous QTL studies have identified 24 QTLs for body weight and growth from 3 to 10 weeks after birth in an intersubspecific backcross mouse population between C57BL/6J and wild Mus musculus castaneus that has 60% of the body size of C57BL/6J. The castaneus allele at the most potent QTL (Pbwg1) on proximal chromosome 2 retards growth. In this study we have developed a congenic strain with a 44.1-Mb interval containing the castaneus allele at Pbwg1 by recurrent backcrossing to C57BL/6J. The congenic mouse developed was characterized by significantly higher body weight gain between 1 and 3 weeks of age and lower weight of white fat pads at 10 weeks of age than C57BL/6J. However, no clear difference in body weight at 1-10 weeks of age was observed between congenic and C57BL/6J strains. QTL analysis with 269 F-2 mice between the two strains did not identify any QTLs for body weight at 1, 3, 6, and 10 weeks of age, but it discovered eight closely linked QTLs affecting body weight gain from 1 to 3 weeks of age, lean body weight, weight of white fat pads, and body length within the Pbwg1 region. The castaneus alleles at all fat pad QTLs reduced the phenotypes, whereas at the remaining growth and body composition QTLs, they increased the trait values. These results illustrate that Pbwg1, which initially appeared to be a single locus, was resolved into several loci with opposite effects on the composition traits of overall body weight. This gives a reason for the loss of the Pbwg1 effect found in the original backcross population.