Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Transgenic Res. 2011 Dec;20(6):1305-20. doi: 10.1007/s11248-011-9499-5. Epub 2011 Mar 2.
Attenuation of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis results in extended lifespan in many organisms including mice. Conversely, GH transgenic mice have excess GH action and die prematurely. We have studied bovine (b) GH transgenic mice (n = 9) and their wild type (WT) littermates (n = 8) longitudinally and have determined several age-related changes. Compared to WT mice, bGH mice lost fat mass, became hypoglycemic and had lower insulin levels at older ages despite being hyperinsulinemic when young. To examine plasma protein differences in bGH mice relative to controls, samples at 2, 4, 8, 12 and 16 months of age were analyzed by two-dimensional gel electrophoresis followed by identification using mass spectrometry. We found several differences in plasma proteins of bGH mice compared to controls, including increased apolipoprotein E (five isoforms), haptoglobin (four isoforms) and mannose-binding protein-C (one out of three isoforms), and decreased transthyretin (six isoforms). In addition, clusterin (two out of six isoforms) and haptoglobin (four isoforms) were up-regulated in bGH mice as a function of age. Finally, alpha-2 macroglobulin (seven isoforms) was altered in an isoform-specific manner with two isoforms increased and two decreased in bGH mouse plasma compared to controls. In conclusion, identification of these proteins suggests that bGH mice exhibit an increased inflammatory state with an adverse lipid profile, possibly contributing to their diminished life expectancy. Also, these newly discovered plasma proteins may be indicative or 'biomarkers' of a shortened lifespan.
生长激素（GH）/胰岛素样生长因子-1（IGF-1）轴的衰减会导致许多生物体（包括老鼠）的寿命延长。相反，GH 转基因小鼠具有过多的 GH 作用，会过早死亡。我们已经对牛（b）GH 转基因小鼠（n=9）及其野生型（WT）同窝仔鼠（n=8）进行了纵向研究，并确定了一些与年龄相关的变化。与 WT 小鼠相比，bGH 小鼠在老年时失去了脂肪量，变得低血糖，胰岛素水平较低，尽管年轻时胰岛素水平较高。为了检查 bGH 小鼠相对于对照的血浆蛋白差异，我们在 2、4、8、12 和 16 个月大时分析了样本，并通过二维凝胶电泳进行分析，然后使用质谱进行鉴定。与对照相比，我们发现 bGH 小鼠的血浆蛋白存在几种差异，包括载脂蛋白 E（五种同工型）、触珠蛋白（四种同工型）和甘露糖结合蛋白-C（三种同工型中的一种）增加，转甲状腺素蛋白（六种同工型）减少。此外，作为年龄的函数，bGH 小鼠中的簇蛋白（两种同工型中的两种）和触珠蛋白（四种同工型）被上调。最后，α-2 巨球蛋白（七种同工型）以同工型特异性的方式发生改变，与对照相比，bGH 小鼠血浆中的两种同工型增加，两种同工型减少。总之，这些蛋白质的鉴定表明，bGH 小鼠表现出炎症状态增加和不良的脂质谱，这可能导致其预期寿命缩短。此外，这些新发现的血浆蛋白可能是寿命缩短的指示物或“生物标志物”。
