Cloning by nuclear transfer from adult somatic cells is a remarkable demonstration of developmental plasticity. When a nucleus is placed in oocyte cytoplasm, the changes in chromatin structure that govern differentiation can be reversed, and the nucleus can be made to control development to term.
Vertebrates have consistent differences between their left and right sides. In all species, nodal, a transforming growth factor ␤ superfamily signalling protein, is involved in a late step in the pathways that specify such asymmetry in the embryo. Earlier components seem not so well conserved. Ancient man may not have known what all our organs did, but no… (More)
The origin of left-right asymmetry during vertebrate embryogenesis has long been a puzzle; now, for the first time, genes have been identified that are expressed with left-right asymmetric patterns in early embryos. Unlike some politicians, vertebrate embryos can tell their left from right. The body plan of vertebrates, although externally symmetrical about… (More)
Genome editing tools enable efficient and accurate genome manipulation. An enhanced ability to modify the genomes of livestock species could be utilized to improve disease resistance, productivity or breeding capability as well as the generation of new biomedical models. To date, with respect to the direct injection of genome editor mRNA into livestock… (More)
Large animal models are an important resource for the understanding of human disease and for evaluating the applicability of new therapies to human patients. For many diseases, such as cone dystrophy, research effort is hampered by the lack of such models. Lentiviral transgenesis is a methodology broadly applicable to animals from many different species.… (More)
Organophosphorus (OP) insecticide self-poisoning is responsible for about one-quarter of global suicides. Treatment focuses on the fact that OP compounds inhibit acetylcholinesterase (AChE); however, AChE-reactivating drugs do not benefit poisoned humans. We therefore studied the role of solvent coformulants in OP toxicity in a novel minipig model of… (More)
BACKGROUND The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. METHOD 35kg pigs were maintained… (More)
Most muscle originates from the myotomal compartment of the somites, paired structures flanking the neural tube. Whereas vertebrate embryos show molecular and morphological asymmetry about the left-right body axis, somitic myogenesis is thought to occur symmetrically. Here, we provide the first evidence that myotome pairs are transiently left-right… (More)
We describe a fundamentally novel feat of animal genetic engineering: the precise and efficient substitution of an agronomic haplotype into a domesticated species. Zinc finger nuclease in-embryo editing of the RELA locus generated live born domestic pigs with the warthog RELA orthologue, associated with resilience to African Swine Fever. The ability to… (More)
The origin of left-right developmental asymmetry is a continuing puzzle, but some recent results provide new insights into the steps leading to organ asymmetry - implicating the homeobox protein Pitz-2 in one key step - and others support a model of symmetry-breaking that involves the chirality of microtubules.