The intrinsic apoptotic pathway is controlled by the BCL-2 family of proteins, which exhibit either a pro-death or pro-survival function. Gene knockout studies revealed that different pro-survival BCL-2 proteins are critical for the survival of distinct cell types, although overlapping functions amongst such proteins have also been identified. In the process of studying mice lacking single alleles of Mcl-1 (Mcl-1^+/−), Bcl-2 (Bcl-2^+/−), or both in combination (Mcl-1^+/−Bcl-2^+/−), we observed that Mcl-1^+/−Bcl-2^+/− mice weighed less when compared with their wild-type littermates as they aged. Body composition analysis demonstrated that while fat mass was similar to wild-type controls, lean mass was significantly reduced in Mcl-1^+/−, Bcl-2^+/−, and, most strikingly in Mcl-1^+/−Bcl-2^+/− mice. The weights of several tissues including the heart, tibialis anterior, and kidney were likewise reduced in Mcl-1^+/−Bcl-2^+/− mice. When lean mass and specific tissue weights were expressed relative to body weight, these differences were no longer significant, indicating that that Mcl-1^+/−Bcl-2^+/− mice, and to a lesser extent Mcl-1^+/− and Bcl-2^+/− mice, are smaller than their wild-type counterparts. Consistently, the anal-naso length was reduced in Mcl-1^+/−Bcl-2^+/− mice. While minor reductions in size were observed in female Mcl-1^+/−Bcl-2^+/− mice, these effects were most prominent in males. Notably, Mcl-1^+/−Bcl-2^+/− males had markedly smaller testes even after accounting for differences in body weight. Collectively, these data reveal that combined loss of a single allele of Mcl-1 and Bcl-2, while not overtly impairing organismal development, leads to a reduction in animal size.

固有的凋亡途径受BCL-2家族蛋白的控制，该家族蛋白具有促死亡或促生存功能。基因敲除研究表明，不同的前生存期BCL-2蛋白对于不同细胞类型的生存至关重要，尽管这种蛋白之间的重叠功能也已被确定。在研究缺少Mcl-1（Mcl-1 ^+/-），Bcl-2（Bcl-2 ^+/-）或两者组合（Mcl-1 ^+/- Bcl-2 ^{+ / -}），我们观察到Mcl-1 ^+/- Bcl-2 ^+/-与野生型同窝仔相比，它们的体重要轻一些。身体组成分析表明，尽管脂肪量是相似的野生型对照，瘦体重是显著降低MCL-1 ^+/-，Bcl-2的^+/-，和最明显地显现在Mcl-1的^+/- Bcl-2的^+/-小鼠。在Mcl-1 ^+/- Bcl-2 ^+/-小鼠中，包括心脏，胫骨前肌和肾脏在内的几种组织的重量同样减少。当瘦体重和特定组织重量相对于体重表达时，这些差异不再显着，表明Mcl-1 ^+/- Bcl-2 ^+/-小鼠，在较小程度上，Mcl-1 ^+/-和Bcl-2 ^+/-小鼠比野生型小鼠小。一致地，在Mcl-1 ^+/- Bcl-2 ^+/-小鼠中肛门鼻长度减小。尽管在雌性Mcl-1 ^+/- Bcl-2 ^+/-小鼠中观察到大小略有减小，但这些作用在雄性中最为明显。值得注意的是，即使考虑了体重差异，Mcl-1 ^+/- Bcl-2 ^+/-男性的睾丸也明显较小。总体而言，这些数据表明，Mcl-1和Bcl-2单个等位基因的综合损失尽管不会明显损害机体发育，但会导致动物体型缩小。