Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies).
ABSTRACT The neonatal abnormalities, treatments and outcomes in a group of 13 cloned transgenic calves and fetuses that progressed into the third trimester of pregnancy are described. From these 13 fetuses, 8 calves were born live, 4 stillborn fetuses were recovered from 3 cows that died 7 d to 2 mo before term, and 1 aborted fetus was recovered at 8 mo gestation. All fetuses and calves were derived from the same male fetal Holstein fibroblast cell line transfected with a beta-galactosidase marker gene. Six calves were delivered by Cesarian section and two by vaginal delivery between 278 and 288 d of gestation. Birth weights ranged from 44 to 58.6 kg. Five of the 8 live born calves were judged to be normal within 4 h of birth based on clinical signs and blood gas measurements. One of these 5 calves died at 6 wk of age from a suspected dilated cardiomyopathy. Three of the 8 calves were diagnosed with neonatal respiratory distress immediately following birth, one of which died (at 4 d of age) as a result of pulmonary surfactant deficiency coupled with pulmonary hypertension and elevated systemic venous pressures. Similar findings of chronic pulmonary hypertension were also observed in 2 of 5 fetuses. Placental edema was present in both calves that later died and in the 2 fetuses with cardiopulmonary abnormalities. Hydrallantois occurred with or without placental edema in 6 cows, and only 1 calf from this group survived. The 6 cows without hydrallantois or placental edema produced 5 live calves and 1 aborted fetus. The cardiopulmonary abnormalities observed in the calves and fetuses occurred in utero in conjunction with placental abnormalities, and it is likely that the cloning technique and/or in vitro embryo culture conditions contributed to these abnormalities, although the mechanism remains to be determined.
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ABSTRACT: Ten pairs of twin lambs 118--122 days of gestation were given either natural surfactant or diluent endotracheally before the first breath. By using the premature twin lamb model, we have been able to show that instillation of natural surfactant produced 100% survival for the duration of the study period (2 hr); stable blood gases on room air; lungs that became increasingly compliant while on the respirator; generally well aerated lungs at autopsy; good lung pressure-volume relationships; normal lung surface tension measurements; and histologic evidence of good alveolar expansion with large amounts of free intraluminal phospholipid, no epithelial damage, and no hyaline membranes. It is concluded that tracheal instillation of natural surfactant into the premature lamb protects the lungs from developing many features characteristic of the respiratory distress syndrome.Pediatric Research 09/1978; 12(8):841-8. · 2.67 Impact Factor
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ABSTRACT: Nuclear transfer has been used in mammals as both a valuable tool in embryological studies and as a method for the multiplication of 'elite' embryos. Offspring have only been reported when early embryos, or embryo-derived cells during primary culture, were used as nuclear donors. Here we provide the first report, to our knowledge, of live mammalian offspring following nuclear transfer from an established cell line. Lambs were born after cells derived from sheep embryos, which had been cultured for 6 to 13 passages, were induced to quiesce by serum starvation before transfer of their nuclei into enucleated oocytes. Induction of quiescence in the donor cells may modify the donor chromatin structure to help nuclear reprogramming and allow development. This approach will provide the same powerful opportunities for analysis and modification of gene function in livestock species that are available in the mouse through the use of embryonic stem cells.Nature 04/1996; 380(6569):64-6. · 38.60 Impact Factor
- New England Journal of Medicine 06/1972; 286(20):1077-81. · 51.66 Impact Factor