Expression of insulin-like growth factors systems in cloned cattle dead within hours after birth.

Cloning by somatic nuclear transfer is an inefficient process in which many of the cloned animals die shortly after birth and display organ abnormalities. In an effort to determine the possible roles IGFs played in neonatal death and organ abnormalities, we have examined expression patterns of eight genes in insulin-like growth factor (IGF) systems (IGF1, IGF2, IGF1R, IGF2R, IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4) in six organs (heart, liver, spleen, lung, kidney, and brain) of both neonatal death cloned bovines (n = 9) and normal control calves (n = 3) produced by artificial insemination (AI) using real-time quantitative RT-PCR. The effect of the age of the fibroblast donor cell on the gene expression profiles was also investigated. Aberrant expressions of six genes (IGF2, IGF1R, IGF2R, IGFBP-2, IGFBP-3, and IGFBP-4) were found in some studied tissues, but the expression of two genes (IGF1 and IGFBP-1) had similar levels with the normal controls. For the studied genes, kidney was the organ that was most affected (five genes) by gene downregulation, whereas spleen was the organ that was not affected. The two upregulation genes were in brain, but both of downregulation and upregulation were found in the heart, liver, and lung. The expression of three genes (IGF2R, IGFBP-4, and IGF2) in some tissues showed significant differences between AF cell-derived and FF cell-derived clones. Our results suggest that aberrations in gene expression within IGF systems were found in most cloned bovine tissues of neonatal death. Because IGF systems play an important role in embryo development and organogenesis, the aberrant transcription patterns detected in these clones may contribute to the defects of organs reported in neonatal death of clones.