Betts Dean H, Perrault Steven D, Petrik Jim, Lin Lucy, Favetta Laura A, Keefer Carol L, King W Allan
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Mol Reprod Dev. 2005 Dec;72(4):461-70. doi: 10.1002/mrd.20371.
Incomplete epigenetic reprogramming of the donor genome is believed to be the cause behind the high rate of developmental mortality and post-natal anomalies observed in animal clones. It appears that overt phenotypic abnormalities are not transmitted to their progeny suggesting that epigenetic errors are corrected in the germline of clones. Here, we show variation in telomere lengths among Nigerian dwarf goat clones derived from different somatic cell types and that the offspring of two male clones have significantly shorter telomere lengths than age-matched noncloned animals. Telomere lengths were significantly shorter in skin biopsies of goat clones derived from adult granulosa cells compared to those measured for controls. Telomere lengths were highly variable in male goat clones reconstructed from fetal fibroblasts but their mean terminal repeat fragment (TRF) length was within normal range of normal goats. However, in the progeny of two male clones, mean TRF lengths were considerably shorter than age-matched controls for both skin and leukocyte samples. Evidence for possible inheritance of shortened telomeres was obtained by measuring telomere lengths in testicular biopsies obtained from the clones, which when compared with those from noncloned animals of a similar age were significantly shorter. The offspring exhibited telomere lengths intermediate to the TRF values obtained for their cloned fathers' and age-matched control testes. These results demonstrate that telomere length reprogramming in clones is dependent on the type of donor cell used and that the progeny of clones may inherit telomere length alterations acquired through the cloning procedure.
供体基因组不完全的表观遗传重编程被认为是动物克隆中观察到的高发育死亡率和出生后异常率背后的原因。明显的表型异常似乎不会传递给它们的后代,这表明表观遗传错误在克隆的种系中得到了纠正。在这里,我们展示了来自不同体细胞类型的尼日利亚矮山羊克隆之间端粒长度的差异,并且两个雄性克隆的后代的端粒长度明显短于年龄匹配的非克隆动物。与对照组相比,来自成年颗粒细胞的山羊克隆的皮肤活检中端粒长度明显更短。从胎儿成纤维细胞重建的雄性山羊克隆中端粒长度高度可变,但它们的平均末端重复片段(TRF)长度在正常山羊的正常范围内。然而,在两个雄性克隆后代中,皮肤和白细胞样本的平均TRF长度均明显短于年龄匹配的对照组。通过测量从克隆获得的睾丸活检中的端粒长度获得了端粒缩短可能遗传的证据,与年龄相似的非克隆动物相比,克隆的睾丸活检中的端粒长度明显更短。这些后代的端粒长度介于其克隆父亲和年龄匹配的对照睾丸获得的TRF值之间。这些结果表明,克隆中端粒长度重编程取决于所使用的供体细胞类型,并且克隆后代可能继承通过克隆程序获得的端粒长度改变。