Thomas A D, Murray J D, Oberbauer A M
Department of Animal Science, University of California Davis, CA 95616, USA.
Transgenic Res. 2005 Aug;14(4):441-8. doi: 10.1007/s11248-005-4349-y.
Most studies utilizing transgenic technology focus on the impact to traits of interest, rather than propagation of the transgene to offspring. In animals containing growth hormone constructs, transgene transmission to progeny follows a Mendelian pattern of inheritance in the first few generations following generation of a founder animal, but decreases in subsequent generations. In the present study, the ovine metallothionein 1a-ovine growth hormone (oMt1a-oGH) transgenic mouse was used to determine whether transgene transmission rate to progeny was affected by overexpression of ovine growth hormone in the transgenic parent. The oMt1a-oGH mouse is a useful model for assessing transgene transmission, as the construct is easily regulatable and transgene inactivation results in a return of plasma GH to basal levels. Male and female hemizygous oMt1a-oGH mice were assigned to 1 of 3 treatment groups: (1) mice never actively expressing the transgene, (2) mice actively expressing the transgene from 3 weeks of age, and (3) mice actively expressing the transgene from 3 to 11 (males) or 3 to 8 (females) weeks of age. Transgenic mice were mated to wild type animals and the resulting progeny were genotyped. Males never actively expressing the transgene passed on the transgene to progeny in a Mendelian fashion, while males actively expressing the transgene transmitted the transgene to a smaller than expected number of progeny. However, following inactivation of the oMt1a-oGH construct in transgenic males, subsequent offspring demonstrated Mendelian inheritance of the transgene. In contrast, females expressing the transgene from 3 to 8 weeks of age were able to pass on the oMt1a-oGH construct in a Mendelian fashion, but females from other treatment groups were not. In oMt1a-oGH males, reduced transgene transmission appears to be due to selection against transgenic gametes. In females, however, selection against the transgenic genotype likely occurs at the embryonic level.
大多数利用转基因技术的研究关注的是对目标性状的影响，而非转基因向后代的传递。在含有生长激素构建体的动物中，转基因向后代的传递在奠基动物产生后的最初几代遵循孟德尔遗传模式，但在随后的几代中会减少。在本研究中，使用绵羊金属硫蛋白1a-绵羊生长激素（oMt1a-oGH）转基因小鼠来确定转基因亲本中绵羊生长激素的过表达是否会影响向后代的转基因传递率。oMt1a-oGH小鼠是评估转基因传递的有用模型，因为该构建体易于调控，且转基因失活会使血浆生长激素水平恢复到基础水平。将雄性和雌性半合子oMt1a-oGH小鼠分配到3个处理组中的1组：（1）从未主动表达转基因的小鼠，（2）从3周龄开始主动表达转基因的小鼠，以及（3）从3至11周龄（雄性）或3至8周龄（雌性）主动表达转基因的小鼠。将转基因小鼠与野生型动物交配，并对产生的后代进行基因分型。从未主动表达转基因的雄性以孟德尔方式将转基因传递给后代，而主动表达转基因的雄性将转基因传递给后代的数量少于预期。然而，在转基因雄性中oMt1a-oGH构建体失活后，随后的后代显示出转基因的孟德尔遗传。相比之下，在3至8周龄表达转基因的雌性能够以孟德尔方式传递oMt1a-oGH构建体，但其他处理组的雌性则不能。在oMt1a-oGH雄性中，转基因传递减少似乎是由于对转基因配子的选择。然而，在雌性中，对转基因基因型的选择可能发生在胚胎水平。
