Status of Cloning of Domestic Animals
Live young have been produced by nuclear transfer in all major domestic mammalian species: cats, dogs, horses, cattle, buffalo, goats, sheep, pigs, and camels.
Cloning in cats appears to be repeatably successful; oocytes may be obtained using tissue recovered from clinical ovariohysterectomies. Interspecies cloning of closely related nondomestic cat species using domestic cat oocytes has produced live young.
Cloning in dogs is complicated by several factors. Mature canine oocytes must be obtained from the oviduct after ovulation, because effective methods for in vitro maturation of canine oocytes have not been developed; additionally, bitches are in estrus only about once every 6 months, so oocyte availability is low and synchronization of recipients is problematic. However, dog cloning is offered by several commercial cloning companies and has been successful in producing puppies.
Cloning in horses results in a low blastocyst development rate (3%–10%), but viability after transfer is among the highest reported; ~30% of transferred embryos produce live foals, and postnatal survival is high (>85%). In one report, 50% of live-born cloned foals had some health issues, including neonatal maladjustment, contracted front legs, and enlarged umbilicus, which resolved with medical care. Recently, production of cloned foals using mesenchymal stem cells isolated from bone marrow has been reported to increase the proportion of foals produced by somatic cell nuclear transfer (SCNT) that are totally healthy at birth. The potential for normality of cloned horses has been demonstrated by their success in competition, including in the demanding sport of polo.
Cloning in food animal species is facilitated by the ready availability of oocytes from slaughterhouse tissue. Cloning in sheep and cattle is inefficient (5%–15% of transferred embryos result in live young), and 30%–50% of live neonates die by 4 years of age. Less information is available on buffalo, but the efficiency appears to be similar. Cloning in sheep and cattle is associated with frequent placental abnormalities, especially low numbers of atypically large cotyledons. There is a high incidence of large offspring syndrome in cloned calves and lambs (ie, fetal overgrowth with related abnormalities), which is thought to be related to placental malfunction. The incidence of large offspring syndrome has been decreased by changes in the in vitro culture environment (notably, reduction in the use of serum in culture media) but has not been totally eliminated.
Little recent information is available on the health of cloned calves, and this appears to differ among laboratories, based on methods used during the cloning process. Cloned calves born live may require extensive medical care; they have been shown to have increased incidence of transient metabolic abnormalities such as hypoglycemia or poor renal function, as well as cardiac abnormalities, which again largely resolve by 30 days after birth. In a 2009 report regarding more than 400 cloned calves, 16% were stillborn, 14% died between birth and 24 hours (the majority from respiratory problems), and 24% died from disease from day 2 to day 150. These rates were all significantly higher than those for conventionally bred calves. However, loss in SCNT-derived cattle surviving more than 200 days after birth was similar to that for conventionally bred cattle. Adult cloned cattle have performed successfully as milk producers, with no difference in milk production from noncloned cattle, and in competition (eg, bucking bulls).
Cloning in goats has similar efficiency in production of live young per embryo transferred (~10%), but cloned kids tend to have greater viability than offspring of sheep and cattle. Goat oocytes are typically obtained by follicle aspiration ex vivo, and this may increase viability of resulting clones.
In pigs, 1%–5% of transferred recombined oocytes produce live young, but cloning is made practicable by the ready availability of large numbers of oocytes and the ability to transfer hundreds of recombined oocytes to the oviducts of a single recipient. Cloned piglets are generally healthy; they have a higher than normal incidence of stillbirth and of some abnormalities but do not develop large offspring syndrome.
Although there are several reports of production of full-term cloned camel calves, essentially no information was provided on their health status.