RESEARCH ARTICLE Molecular Reproduction & Development 78:337–346 (2011) Morphological Abnormalities, Impaired Fetal Development and Decrease in Myostatin Expression Following Somatic Cell Nuclear Transfer in Dogs IL-HWA HONG, 1 YEON-WOO JEONG, 2 TAEYOUNG SHIN, 2 SANG-HWAN HYUN, 3 JIN-KYU PARK, 1 MI-RAN KI, 1 SEON-YOUNG HAN, 1 SE-IL PARK, 1 JI-HYUN LEE, 4 EUN-MI LEE, 1 AH-YOUNG KIM, 1 SANG-YOUNG YOU, 1 WOO-SUK HWANG, 2 ** AND KYU-SHIK JEONG 1,5 * 1 College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea 2 SooAm Biotech Research Foundation, Seoul, Republic of Korea 3 Laboratory of Veterinary Biotechnology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea 4 Department of Genetics, Center of Human Genetic Research Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 5 Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of Korea SUMMARY Several mammals, including dogs, have been successfully cloned using somatic cell nuclear transfer (SCNT), but the efficiency of generating normal, live offspring is relatively low. Although the high failure rate has been attributed to incomplete reprogramming of the somatic nuclei during the cloning process, the exact cause is not fully known. To elucidate the cause of death in cloned offspring, 12 deceased offspring cloned by SCNT were necropsied. The clones were either stillborn just prior to delivery or died with dyspnea shortly after birth. On gross examination, defects in the anterior abdominal wall and increased heart and liver sizes were found. Notably, a significant increase in muscle mass and macroglossia lesions were observed in deceased SCNT-cloned dogs. Interestingly, the expression of myostatin, a negative regulator of muscle growth during embryogenesis, was down-regulated at the mRNA level in tongues and skeletal muscles of SCNT-cloned dogs compared with a normal dog. Results of the present study suggest that decreased expression of myostatin in SCNT-cloned dogs may be involved in morphological abnormalities such as in- creased muscle mass and macroglossia, which may contribute to impaired fetal development and poor survival rates. Mol. Reprod. Dev. 78: 337–346, 2011. ß 2011 Wiley-Liss, Inc. Received 15 August 2010; Accepted 6 March 2011 * Corresponding author: College of Veterinary Medicine Kyungpook National University Daegu, Republic of Korea. E-mail: jeongks@knu.ac.kr ** Corresponding author: SooAm Biotech Research Foundation 1027-4 SooAm Building Seoul, Republic of Korea. E-mail: hwangws@sooam.org Published online 23 April 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/mrd.21309 INTRODUCTION Mammals have been successfully cloned for several years by transferring nuclei from somatic cells into enucle- ated oocytes. Cloning dogs by somatic cell nuclear transfer Abbreviations: BWS, Beckwith–Wiedemann syndrome; IGF, insulin like growth factor; IVP, in vitro-produced; LOS, large offspring syndrome (also, abnormal offspring syndrome); MFD, mean lesser fiber diameter; MRF, myo- genic transcriptional regulatory factor; MRF4, myogenic factor 6; Myf-5, myo- genic factor 5; MyoD, myogenic differentiation 1; SCNT, somatic cell nuclear transfer. ß 2011 WILEY-LISS, INC.