Metabolomic phenotyping of a cloned pig model

Abstract

BackgroundPigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal outbred pigs.ResultsThe metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n = 6) by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could not be established.ConclusionsFrom the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals.

Expression of Innate Immune Response Genes in Liver and Three Types of Adipose Tissue in Cloned Pigs

“…In accordance with other studies reporting on interindividual variability in pigs cloned by SCNT (Clausen et al, 2011;Hwang et al, 2009;Park et al, 2011;Whyte et al, 2011), we were not able to show significant differences between clones and controls in the interindividual variability in expression of 40 immune system-related genes in the four different tissues. The variability of serum concentrations of two of three serum proteins investigated was also similar in clones and controls, whereas the last serum protein (ORM) was significantly less variable in cloned pigs.…”

“…Although it is normally assumed that the use of cloned animals will exhibit less interindividual phenotypic variation and allow for a reduction of the number of animals needed to obtain statistically sound data, this assumption has been found not always to be warranted. For example, the variability in blood parameters and metabolites (Archer et al, 2003;Clausen et al, 2011) as well as the gene expression of fetal growth-related genes ( Jiang et al, 2007) was found to be similar in cloned as in normal pigs. It has been proposed that some of this variation may stem from maternal mitochondrial DNA from the donor cell (St. John et al, 2005).…”

“…Surviving cloned pigs are generally found to be healthy and production and reproduction properties in adult cloned pigs are generally normal; however, there are several reports of cloned pigs having deviant phenotypes. These include pulmonary hypertension and other hemodynamic disorders, contracted foreleg tendons, and respiratory problems (Whyte et al, 2011), changes in metabolic phenotype (Christensen et al, 2012;Clausen et al, 2011), and a higher incidence of mild atelectasis (Park et al, 2011). Lower body weight is a common finding in cloned pigs, both at birth and later (Archer et al, 2003;Jiang et al, 2007;Park et al, 2011;Tian et al, 2008), although it is not always observed (Carter et al, 2002).…”

The effect of high-fat diet on the composition of the gut microbiota in cloned and non-cloned pigs of lean and obese phenotype

“…The cloned embryos were subsequently transferred surgically to surrogate sows (recipients) five to six days after cloning. 4 Five surrogate sows gave birth to a total of 17 female cloned pigs, during a period of three years. The non-cloned pigs (n = 19) (75% L × 25% Y) were obtained from 6 sows after standard…”

“…Cloning of pigs has been performed previously primarily by somatic cell nuclear transfer but this method often results in low numbers of cloned animals due to loss of embryos either during the gestation period or death of the piglets shortly after birth. 2,3 It has been suggested that cloning gives rise to altered metabolic characteristics, 4 skin abnormalities 5,6 and other physiological defects which may limit the use of cloned animals as experimental models. However so far there is only one study that has explored the gut microbiota in obese cloned pigs.…”