生物谷报道：在新一期的BMC Genetics杂志的网络版上，来自Monell中心的研究人员首次尝试估算出控制肥胖和体重的基因数量。他们的研究发现有超过6000个基因（大约占基因组的25％）帮助确定一个人的体重。
研究人员表示，他们的研究结果暗示出，之前一些研究发现的每个与体重有关的基因只是数千个影响体重的基因中的一个而已，因此快速地解决体重问题是不可能的。
为了能够估计出影响体重的基因数量，Monell的研究人员研究了Jackson实验室小鼠基因组数据库，寻找与敲除小鼠的体重有关的信息。
每个敲除小鼠都有一个特定的基因被失活。通过研究这些敲除小鼠与正常小鼠的差异，研究人员能够获得基因功能以及是否导致疾病发生的信息。小鼠能够提供有关人类疾病的有用信息，这是因为它们具有与人类相同的很多基因。
这种敲除方法非常有用，2007年诺贝尔生理医学奖就颁发给了这项技术的发明者。敲除小鼠目前是所有行为和疾病小鼠模型的标准研究工具。
在60％的小鼠株中，敲除一个基因会导致小鼠无法存活。Monell的研究发现，体重情况在超过三分之一的可存活敲除小鼠中发生了改变；31％使体重比对照轻，而另外3％则使体重增加了。
根据小鼠基因组中的基因数量进行推算，这意味着有超过6000个基因可能影响小鼠的体重。
研究人员评论说，这项研究的研究很尤其，它揭示出促进体重增加的基因数量是使体重减少的基因数量的10倍——这也可能解释了为什么增加体重比减肥更容易。
因为体重是许多疾病的一个影响因子，包括高血压、糖尿病和心脏病。这些新发现的意义在于超越了之前的肥胖和体重研究。影响这些疾病和其他疾病的基因敲除信息的公布将有可能对减少体重产生广泛影响。
这些发现还具有临床意义。医生和其他关心个性化医疗发展的专业人员需要拓宽他们的遗传学思路，要意识到许多基因一起作用才能决定疾病的敏感性。
生物谷推荐原始出处：
BMC Genetics
Reduced body weight is a common effect of gene knockout in mice
Danielle R Reed , Maureen P Lawler and Michael G Tordoff
BMC Genetics 2008, 9:4doi:10.1186/1471-2156-9-4
Published: 8 January 2008
Background
During a search for obesity candidate genes in a small region of the mouse genome, we noticed that many genes when knocked out influenced 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.
Results
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 31% of viable knockout mouse strains weighed less and an additional 3% weighed more than did controls.
Conclusions
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.
