• 1.

    Wilmut I, Schnieke AE & McWhir J, et al. Viable offspring derived from fetal and adult mammalian cells. Nature 1997;385:810813.

  • 2.

    Fecteau ME, Palmer JE, Wilkins PA. Neonatal care of high-risk cloned and transgenic calves. Vet Clin North Am Food Anim Pract 2005;21:637653.

    • Search Google Scholar
    • Export Citation
  • 3.

    Campbell KH, Alberio R & Choi I, et al. Cloning: eight years after Dolly. Reprod Domest Anim 2005;40:256268.

  • 4.

    Keefer CL. Lessons learned from nuclear transfer (cloning). Theriogenology 2008;69:4854.

  • 5.

    Oback B. Climbing mount efficiency—small steps, not giant leaps towards higher cloning success in farm animals. Reprod Domest Anim 2008;43(suppl 2):407416.

    • Search Google Scholar
    • Export Citation
  • 6.

    Hashizume K, Ishiwata H & Kizaki K, et al. Implantation and placental development in somatic cell clone recipient cows. Cloning Stem Cells 2002;4:197209.

    • Search Google Scholar
    • Export Citation
  • 7.

    Hill JR, Burghardt RC & Jones K, et al. Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses. Biol Reprod 2000;63:17871794.

    • Search Google Scholar
    • Export Citation
  • 8.

    Kohan-Ghadr HR, Lefebvre RC & Fecteau G, et al. Ultrasonographic and histological characterization of the placenta of somatic nuclear transfer-derived pregnancies in dairy cattle. Theriogenology 2008;69:218230.

    • Search Google Scholar
    • Export Citation
  • 9.

    Wilmut I. Are there any normal clones? Methods Mol Biol 2006;348:307318.

  • 10.

    Hill JR, Roussel AJ & Cibelli JB, et al. Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies). Theriogenology 1999;51:14511465.

    • Search Google Scholar
    • Export Citation
  • 11.

    Heyman Y, Chavatte-Palmer P & LeBourhis D, et al. Frequency and occurrence of late-gestation losses from cattle cloned embryos. Biol Reprod 2002;66:613.

    • Search Google Scholar
    • Export Citation
  • 12.

    Batchelder CA, Bertolini M & Mason JB, et al. Perinatal physiology in cloned and normal calves: physical and clinical characteristics. Cloning Stem Cells 2007;9:6382.

    • Search Google Scholar
    • Export Citation
  • 13.

    Chavatte-Palmer P, Remy D & Cordonnier N, et al. Health status of cloned cattle at different ages. Cloning Stem Cells 2004;6:94100.

  • 14.

    Chavatte-Palmer P, Heyman Y & Richard C, et al. Clinical, hormonal, and hematologic characteristics of bovine calves derived from nuclei from somatic cells. Biol Reprod 2002;66:15961603.

    • Search Google Scholar
    • Export Citation
  • 15.

    Garry FB, McCann JP, Odde KG. Postnatal characteristics of calves produced by nuclear transfer cloning. Theriogenology 1996;45:141152.

  • 16.

    Kasai K, Sano F & Miyashita N, et al. Comparison of the growth performances of offspring produced by a pair of cloned cattle and their nuclear donor animals. J Reprod Dev 2007;53:135142.

    • Search Google Scholar
    • Export Citation
  • 17.

    Wells DN, Forsyth JT & McMillan V, et al. The health of somatic cell cloned cattle and their offspring. Cloning Stem Cells 2004;6:101110.

  • 18.

    Norman HD, Walsh MK. Performance of dairy cattle clones and evaluation of their milk composition. Cloning Stem Cells 2004;6:157164.

  • 19.

    Takahashi S, Ito Y. Evaluation of meat products from cloned cattle: biological and biochemical properties. Cloning Stem Cells 2004;6:165171.

    • Search Google Scholar
    • Export Citation
  • 20.

    Woods GL, White KL & Vanderwall DK, et al. A mule cloned from fetal cells by nuclear transfer. Science 2003;301:1063.

  • 21.

    Galli C, Lagutina I & Crotti G, et al. Pregnancy: a cloned horse born to its dam twin (Erratum published in Nature 2003;425:680). Nature 2003;424:635.

    • Search Google Scholar
    • Export Citation
  • 22.

    Lagutina I, Lazzari G & Duchi R, et al. Somatic cell nuclear transfer in horses: effect of oocyte morphology, embryo reconstruction method and donor cell type. Reproduction 2005;130:559567.

    • Search Google Scholar
    • Export Citation
  • 23.

    Hinrichs K, Choi YH & Love CC, et al. Production of horse foals via direct injection of roscovitine-treated donor cells and activation by injection of sperm extract. Reproduction 2006;131:10631072.

    • Search Google Scholar
    • Export Citation
  • 24.

    Hinrichs K, Choi YH & Varner DD, et al. Production of cloned horse foals using roscovitine-treated donor cells and activation with sperm extract and/or ionomycin. Reproduction 2007;134:319325.

    • Search Google Scholar
    • Export Citation
  • 25.

    Choi YH, Hartman DL & Fissore RA, et al. Effect of sperm extract injection volume, injection of PLCzeta cRNA, and tissue cell line on efficiency of equine nuclear transfer. Cloning Stem Cells 2009;11:301308.

    • Search Google Scholar
    • Export Citation
  • 26.

    Pollack A. Goodbye Dolly: up from sheep to cloned horses. New York Times 2006;Mar 31:4.

  • 27.

    Vanderwall DK, Woods GL & Sellon DC, et al. Present status of equine cloning and clinical characterization of embryonic, fetal, and neonatal development of three cloned mules. JAMA 2004;225:16941699.

    • Search Google Scholar
    • Export Citation
  • 28.

    Fowden AL, Forhead AJ, Ousey JC. The endocrinology of equine parturition. Exp Clin Endocrinol Diabetes 2008;116:393403.

  • 29.

    Ousey JC, Houghton E & Grainger L, et al. Progestagen profiles during the last trimester of gestation in Thoroughbred mares with normal or compromised pregnancies. Theriogenology 2005;63:18441856.

    • Search Google Scholar
    • Export Citation
  • 30.

    Wilcox AL, Calise DV & Chapman SE, et al. Hypoxic/ischemic encephalopathy associated with placental insufficiency in a cloned foal. Vet Pathol 2009;46:7579.

    • Search Google Scholar
    • Export Citation
  • 31.

    Bauer JE. Normal biochemistry values. In: Koterba AM, Drummond WH, Kosch PC, eds. Equine clinical neonatology. Philadelphia: Lea & Febiger, 1990;602614.

    • Search Google Scholar
    • Export Citation
  • 32.

    Iuliano MF, Squires EL, Cook VM. Effect of age of equine embryos and method of transfer on pregnancy rate. J Anim Sci 1985;60:258263.

  • 33.

    Hinrichs K, Choi YH & Walckenaer BE, et al. In vitro-produced equine embryos: production of foals after transfer, assessment by differential staining and effect of medium calcium concentrations during culture. Theriogenology 2007;68:521529.

    • Search Google Scholar
    • Export Citation
  • 34.

    Oback B. Cloning from stem cells: different lineages, different species, same story. Reprod Fertil Dev 2008;21:8394.

  • 35.

    Dinnyes A, Nedambale TL. Cryopreservation of manipulated embryos: tackling the double jeopardy. Reprod Fertil Dev 2008;21:4559.

  • 36.

    Yazawa S, Aoyagi Y & Konishi M, et al. Characterization and cytogenetic analysis of Japanese Black calves produced by nuclear transfer. Theriogenology 1997;48:641650.

    • Search Google Scholar
    • Export Citation
  • 37.

    Elce YA. Infections in the equine abdomen and pelvis: perirectal abscesses, umbilical infections, and peritonitis. Vet Clin North Am Equine Pract 2006;22:419436.

    • Search Google Scholar
    • Export Citation
  • 38.

    Allen WR, Wilsher S & Turnbull C, et al. Influence of maternal size on placental, fetal and postnatal growth in the horse. I. Development in utero. Reproduction 2002;123:445453.

    • Search Google Scholar
    • Export Citation
  • 39.

    Bain AM, Howey WP. Observations on the time of foaling in thorough-bred mares in Australia. J Reprod Fertil Suppl 1975;(23):545546.

  • 40.

    Roberts S. Diseases and accidents of gestation. In: Roberts SJ, ed. Veterinary obstetrics and genital diseases. 3rd ed. Woodstock, Vt: David and Charles Inc, 1986;224226.

    • Search Google Scholar
    • Export Citation
  • 41.

    Wintour EM, Laurence BM, Lingwood BE. Anatomy, physiology and pathology of the amniotic and allantoic compartments in the sheep and cow. Aust Vet J 1986;63:216221.

    • Search Google Scholar
    • Export Citation
  • 42.

    Knottenbelt DC, Holdstock N, Madigan JE. Congenital abnormalities and inherited disorders. In: Knottenbelt DC, Holdstock N, Madigan JE, eds. Equine neonatology medicine and surgery. Philadelphia: Saunders, 2004;98.

    • Search Google Scholar
    • Export Citation
  • 43.

    Highfield R. World's first cloned horse has foal. The Daily Telegraph. 2008;Apr 29. Available at: www.telegraph.co.uk/science/science-news/3341050/Worlds-first-cloned-horse-has-foal.html. Accessed Feb 23, 2010.

    • Search Google Scholar
    • Export Citation

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Physical and clinicopathologic findings in foals derived by use of somatic cell nuclear transfer: 14 cases (2004–2008)

Aime K. Johnson DVM, DACT1, Stuart C. Clark-Price DVM, MS, DACVIM, DACVA2, Young-Ho Choi DVM, PhD3, David L. Hartman DVM4, and Katrin Hinrichs DVM, PhD, DACT5
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  • 1 Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843.
  • | 2 Performance Equine Associates, 15257 Hwy 377, Whitesboro, TX 76273.
  • | 3 Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843.
  • | 4 Performance Equine Associates, 15257 Hwy 377, Whitesboro, TX 76273.
  • | 5 Departments of Large Animal Clinical Sciences and Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843.

Abstract

Objective—To describe the health status of foals derived by use of somatic cell nuclear transfer (NT) at a university laboratory.

Design—Retrospective case series.

Animals—14 live-born NT-derived foals.

Procedures—Medical records from 2004 through 2008 were evaluated to identify all pregnancies resulting in live-born NT-derived foals. Information obtained included gestation length, birth weight, foaling complications, gross abnormalities of the fetal membranes, appearance of the umbilicus, mentation of the foal, limb deformities, and any other abnormalities detected in the neonatal period. Clinicopathologic data were also evaluated when available. Records of 4 recipient mares during gestation were included.

Results—Six foals were clinically normal for all evaluated variables. The most common abnormalities detected in the remaining 8 foals included maladjustment, enlarged umbilical remnant, and angular deformity of the forelimbs. Two foals died within 7 days after parturition; in the remaining foals, these conditions all resolved with medical or surgical management. Large offspring syndrome and gross abnormalities of the fetal membranes were not detected. The 12 surviving foals remained healthy.

Conclusions and Clinical Relevance—Associated problems of calves resulting from use of NT have been reported, but there are few data on the outcome of foals resulting from adult somatic cell NT in horses. Although this population of foals had a lower perinatal mortality rate than has been reported for NT-derived calves, some NT-derived foals required aggressive supportive care. Birth of foals derived from NT should take place at a center equipped to handle critical care of neonates.

Abstract

Objective—To describe the health status of foals derived by use of somatic cell nuclear transfer (NT) at a university laboratory.

Design—Retrospective case series.

Animals—14 live-born NT-derived foals.

Procedures—Medical records from 2004 through 2008 were evaluated to identify all pregnancies resulting in live-born NT-derived foals. Information obtained included gestation length, birth weight, foaling complications, gross abnormalities of the fetal membranes, appearance of the umbilicus, mentation of the foal, limb deformities, and any other abnormalities detected in the neonatal period. Clinicopathologic data were also evaluated when available. Records of 4 recipient mares during gestation were included.

Results—Six foals were clinically normal for all evaluated variables. The most common abnormalities detected in the remaining 8 foals included maladjustment, enlarged umbilical remnant, and angular deformity of the forelimbs. Two foals died within 7 days after parturition; in the remaining foals, these conditions all resolved with medical or surgical management. Large offspring syndrome and gross abnormalities of the fetal membranes were not detected. The 12 surviving foals remained healthy.

Conclusions and Clinical Relevance—Associated problems of calves resulting from use of NT have been reported, but there are few data on the outcome of foals resulting from adult somatic cell NT in horses. Although this population of foals had a lower perinatal mortality rate than has been reported for NT-derived calves, some NT-derived foals required aggressive supportive care. Birth of foals derived from NT should take place at a center equipped to handle critical care of neonates.

Contributor Notes

Dr. Johnson's present address is the JT Vaughn Large Animal Teaching Hospital, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

Dr. Clark-Price's present address is the Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

Dr. Hartman's present address is Hartman Equine Reproduction Center, 15225 Hwy 377, Whitesboro, TX 76273.

Supported by the Link Equine Research Endowment Fund at Texas A&M University and Cryozootech S.A.

The authors thank Jennifer Pirkle for technical assistance.

Address correspondence to Dr. Johnson (akj0001@auburn.edu).