Eisen E J, Murray J D
Department of Animal Science, North Carolina State University, Raleigh 27695, USA.
J Anim Sci. 2001 Jul;79(7):1734-41. doi: 10.2527/2001.7971734x.
Objectives were to determine whether the oMt1a-oGH transgene shows normal Mendelian segregation and whether oMt1a-oGH mice exhibit normal growth without the zinc supplementation required to increase plasma oGH levels and stimulate growth. Transgenic mice were reciprocally backcrossed for four generations to high growth and control lines to form lines GM and GR, respectively. In the fifth generation, hemizygous transgenic mice (T/-) were crossed within each line. Pooled across backcross generations, there was a deficit (P < 0.001) of T/- progeny in lines GM (31.6%) and GR (22.2%) compared with expected (50%). In the T/- x T/- cross, the combined percentage of homozygous (T/T) and hemizygous transgenic mice was less (P < 0.001) than expected (75%) in both GM (44.2%) and GR (38.5%). Backcross T/- mice had lower (P < 0.05) 3-wk BW and lower (P < 0.001) 6-wk BW and 3- to 6-wk postweaning gains than nontransgenic mice. Similar genotypic differences were found in the T/- x T/- cross. No significant growth differences were found between T/T and T/- progeny. Using segregation ratios from the T/- x T/- mating, the relative fitness estimates of T/T, T/-, and -/- (nontransgenic) mice were 0.345, 0.223, and 1.0, respectively, in line GM and 0.218, 0.205, and 1.0 in line GR. Fitness estimates in the back-cross for T/- and -/- were 0.463 and 1.0 in line GM and 0.285 and 1.0 in line GR. Abnormal segregation ratios may be due to germline mosaicism or reduced fitness due to differential embryo survival. Reduced growth of oMt1a-oGH transgenic mice when the transgene is switched off suggests a subtle developmental abnormality, which may contribute to a reduction in fitness.
目的是确定oMt1a - oGH转基因是否表现出正常的孟德尔分离，以及oMt1a - oGH小鼠在不补充锌以提高血浆oGH水平和刺激生长的情况下是否表现出正常生长。将转基因小鼠与高生长系和对照系分别进行四代相互回交，以分别形成GM系和GR系。在第五代，每个系内的半合子转基因小鼠（T/-）进行杂交。在整个回交世代中，GM系（31.6%）和GR系（22.2%）中的T/-后代比预期（50%）有所减少（P < 0.001）。在T/-×T/-杂交中，纯合（T/T）和半合子转基因小鼠的合并百分比在GM系（44.2%）和GR系（38.5%）中均低于预期（75%）（P < 0.001）。回交的T/-小鼠在3周龄时体重较低（P < 0.05），在6周龄时体重较低（P < 0.001），断奶后3至6周的体重增加也低于非转基因小鼠。在T/-×T/-杂交中也发现了类似的基因型差异。在T/T和T/-后代之间未发现显著的生长差异。利用T/-×T/-交配的分离比，GM系中T/T、T/-和-/-（非转基因）小鼠的相对适合度估计值分别为0.345、0.223和1.0，GR系中分别为0.218、0.205和1.0。T/-和-/-在回交中的适合度估计值在GM系中为0.463和1.0，在GR系中为0.285和1.0。异常的分离比可能是由于生殖系嵌合体或由于胚胎存活率差异导致的适合度降低。当转基因关闭时，oMt1a - oGH转基因小鼠生长减缓表明存在细微的发育异常，这可能导致适合度降低。
