Genetic modifications of pigs for medicine and agriculture

Abstract

SUMMARY Genetically modified swine hold great promise in the fields of agriculture and medicine. Currently, these swine are being used to optimize production of quality meat, to improve our understanding of the biology of disease resistance, and to reduced waste. In the field of biomedicine, swine are anatomically and physiologically analogous to humans. Alterations of key swine genes in disease pathways provide model animals to improve our understanding of the causes and potential treatments of many human genetic disorders. The completed sequencing of the swine genome will significantly enhance the specificity of genetic modifications, and allow for more accurate representations of human disease based on syntenic genes between the two species. Improvements in both methods of gene alteration and efficiency of model animal production are key to enabling routine use of these swine models in medicine and agriculture.

Germline transgenesis in pigs by cytoplasmic microinjection of Sleeping Beauty transposons

“…SCNT is currently the most commonly applied method for porcine transgenesis. The procedure includes gene transfer into primary somatic cells, screening of cells carrying the desired genetic modification, introduction of a genetically modified cell into an enucleated porcine oocyte and activation of the reconstructed embryo to initiate cleavage divisions 3,7,8 . The transfer of >100 reconstructed embryos to one surrogate animal is required to establish a pregnancy in the pig 7,8 and success rates of only 1-3 % per reconstructed embryos have been achieved 7,8 .…”

“…The pig has emerged as an important large mammalian model in biomedical and pharmaceutical research [1][2][3] . Pigs have been widely applied for studying infectious diseases, cardiovascular disease, atherosclerosis, wound healing, diabetes, ophthalmology, cancer and cell therapies, as well as for assessing the suitability of porcine xenotransplants for humans 2,4 .…”

“…Humanized pig models include those for retinitis pigmentosa 6 , cystic fibrosis 7 , Alzheimer´s disease 8 , Huntington´s disease 9 , familial adenomatous polyposis 10 , and immunodeficiency 11 . However, transgenesis in the pig, most commonly achieved by pronuclear DNA injection (PNI) or by somatic cell nuclear transfer (SCNT), is an inefficient and expensive process, hampered by poor predictability of levels and patterns of transgene expression 2,3,[12][13][14] . Gene targeting by homologous recombination is extremely inefficient in porcine somatic cells 3 , and porcine embryonic stem cells (ES) have not yet been established 15 .…”

“…However, transgenesis in the pig, most commonly achieved by pronuclear DNA injection (PNI) or by somatic cell nuclear transfer (SCNT), is an inefficient and expensive process, hampered by poor predictability of levels and patterns of transgene expression 2,3,[12][13][14] . Gene targeting by homologous recombination is extremely inefficient in porcine somatic cells 3 , and porcine embryonic stem cells (ES) have not yet been established 15 . Recently, several groups described the derivation of porcine induced pluripotent cells (iPS) [16][17][18][19][20] , however, only low chimerism has been found after blastocyst complementation experiments 21,22 .…”

Endo-siRNA deficiency results in oocyte maturation failure and apoptosis in porcine oocytes

“…Pigs are important not only in agriculture but also in biomedicine. In the field of biomedicine, pigs are more anatomically and physiologically analogous to humans than mice (Pratt et al 2006;Whyte and Prather 2011). Alterations of porcine key genes in the reproductive pathway provide model animals to improve our understanding of the causes and potential treatments of many human reproductive disorders.…”