Senescence is accelerated through donor cell specificity in cloned pigs

Jeon,Hyun  Yong; Jeong,Yeon  Woo; Kim,Yeon  Wook; Jeong,Yeon Ik; Hossein,Shamim  M.; Yang,Hyun; Hyun,Sang  Hwan; Jeung,Eui-Bae; Hwang,Woo  Suk

doi:10.3892/ijmm.2012.1003

Senescence is accelerated through donor cell specificity in cloned pigs

Authors:
- Hyun Yong Jeon
- Yeon Woo Jeong
- Yeon Wook Kim
- Yeon Ik Jeong
- Shamim M. Hossein
- Hyun Yang
- Sang Hwan Hyun
- Eui-Bae Jeung
- Woo Suk Hwang
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Affiliations: Sooam Biotech Research Foundation, Guro-gu, Seoul 152-904, Republic of Korea, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea
Published online on: May 18, 2012 https://doi.org/10.3892/ijmm.2012.1003
Pages: 383-391

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Abstract

Animals cloned by somatic cell nuclear transfer (SCNT) sometimes have abnormalities that result in large offspring syndrome or early death during gestation due to respiratory and metabolic defects. We cloned pigs using two sources of donor cells and observed phenotypic anomalies in three pigs cloned from one type of cell, s-pig fetal fibroblasts. These animals had many wrinkles on their faces and bodies and looked older than age-matched normal pigs. We performed the present study to examine whether the wrinkled phenotype in the cloned pigs was due to senescence, a genetic problem with donor specificity, or epigenetic problems with reprogramming. To address this issue, we investigated biomarkers of senescence, including telomere length and the expression of senescence-associated β-galactosidase (SA-β-gal), glyceraldehyde phosphate dehydrogenase (GAPDH) and β-actin. We also assessed the methylation status of euchromatic PRE-1 repetitive sequences and centromeric satellite DNA, and measured the mRNA levels of six imprinted genes, Copg2, Mest, Igf2R, GNAS, SNRPN and Ube3a. The telomeres of the wrinkled cloned pigs were much shorter than those of the normal cloned pigs and age-matched normal pigs. In the wrinkled cloned pigs, SA-β-gal activity was detected and GAPDH and β-actin were repressed. The mRNA levels of Mest, GNAS and Ube3a were reduced in the wrinkled cloned pigs, although there was no difference between the normal cloned pigs and normal controls. This gene expression analysis indicates that the wrinkled abnormality of our pigs originates from genetic abnormalities in the donor cells used for SCNT.

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