Reduced body weight is a common effect of gene knockout in mice.
Reduced body weight is a common effect of gene knockout in mice.
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DOI：
10.1186/1471-2156-9-4
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发表时间：
2008-01-08
期刊：
影响因子：
2.9
通讯作者：
Tordoff, Michael G.
中科院分区：
文献类型：
--
作者：
Reed, Danielle R.;Lawler, Maureen P.;Tordoff, Michael G.
在小鼠基因组的一个小区域中寻找肥胖候选基因时，我们注意到许多基因被敲除后会影响体重。为了确定这是基因敲除的一般特征还是偶然发生，我们调查了杰克逊实验室小鼠基因组数据库，了解敲除小鼠品系及其表型。并非所有菌株都有体重，因此我们还通过联系负责敲除菌株的随机调查人员样本来获得体重信息。相对于对照小鼠，我们将每个基因敲除小鼠品系分为（1）较轻和较小，（2）较大和较重，或（3）相同重量。我们排除了在生命早期死亡的敲除菌株，尽管这种类型的致死性通常与胚胎较小或体型减小有关。基于 1,977 个基因敲除小鼠品系的数据集，我们发现 31% 的存活基因敲除小鼠品系比对照小鼠体重更轻，另外 3% 的小鼠体重更重。在大约三分之一使用基因敲除小鼠的实验中，体重可能是一个潜在变量，在解释实验结果时应考虑体重，例如在高血压、药物和激素代谢、器官发育、细胞增殖和凋亡、消化、心率或动脉粥样硬化的研究中。如果我们假设我们调查的敲除基因具有代表性，那么预计有超过 6,000 个基因会影响小鼠的体型。体重具有高度遗传性，并且已在小鼠中绘制了许多数量性状基因座，但“多基因”一词不足以描述可能促成这种复杂性状的数千个基因座。
During a search for obesity candidate genes in a small region of the mouse genome, we noticed that many genes when knocked out influence body weight. To determine whether this was a general feature of gene knockout or a chance occurrence, we surveyed the Jackson Laboratory Mouse Genome Database for knockout mouse strains and their phenotypes. Body weights were not available for all strains so we also obtained body weight information by contacting a random sample of investigators responsible for a knockout strain. We classified each knockout mouse strain as (1) lighter and smaller, (2) larger and heavier, or (3) the same weight, relative to control mice. We excluded knockout strains that died early in life, even though this type of lethality is often associated with a small embryo or reduced body size. Based on a dataset of 1,977 knockout strains, we found that that 31% of viable knockout mouse strains weighed less and an additional 3% weighed more than did controls. Body weight is potentially a latent variable in about a third of experiments that use knockout mice and should be considered in interpreting experimental outcomes, e.g., in studies of hypertension, drug and hormone metabolism, organ development, cell proliferation and apoptosis, digestion, heart rate, or atherosclerosis. If we assume that the knockout genes we surveyed are representative then upward of 6,000 genes are predicted to influence the size of a mouse. Body weight is highly heritable, and numerous quantitative trait loci have been mapped in mice, but "multigenic" is an insufficient term for the thousands of loci that could contribute to this complex trait.
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