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Abstract

Miniature pig is an attractive animal for a wide range of research fields, such as medicine and pharmacology, because of its small size, the possibility of breeding it under minimum environmental controls and the physiology that is potentially similar to that of human. Although transgenic technology is useful for the analysis of gene function and for the development of model animals for various diseases, there have not yet been any reports on producing transgenic miniature pig. This study is the first successful report concerning the production of transgenic miniature pig by pronuclear microinjection. The huntingtin gene cloned from miniature pig, which is a homologue of candidate gene for Huntington's disease, connected with rat neuron-specific enolase promoter region, was injected into a pronucleus of fertilized eggs with micromanipulator. The eggs were transferred into the oviduct of recipient miniature pigs, whose estrus cycles were previously synchronized with a progesterone analogue. A total of 402 injected eggs from 171 donors were transferred to 23 synchronized recipients. Sixteen of them maintained pregnancy and delivered 65 young, and one resulted in abortion. Five of the 68 offspring (three of which were aborted) were determined to have transgene by PCR and Southern analysis. The overall rate of transgenic production was 1.24% (transgenic/injected eggs). This study provides the first success and useful information regarding production of transgenic miniature pig for biomedical research.

Genetically Engineered Pig Models for Human Diseases

“…The first was produced by pronuclear injection and contained a 75-polyQ tract but had no phenotype (91). A second group introduced a 105-polyQ tract into somatic cells and then created the pigs by SCNT (92).…”

Modeling Amyotrophic Lateral Sclerosis in hSOD1G93A Transgenic Swine

“…Bjarkam et al [18] succeeded in producing an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) Parkinson disease pig model, while other research groups developed transgenic pig models for Alzheimer's disease [19], spinal muscular atrophy [20] and Huntington disease [21]. Here we report on the production of 5 healthy transgenic Yucatan minipigs expressing the hSOD1 G93A transgene.…”

Porcine Model of Huntington's Disease

“…In consequence, large animal models of HD, including non-human primate [1], sheep [2] and pigs [3][4][5], have been generated. The advantages of pigs, in particular the minipigs, are the adult body weight of 70-90 kg, relatively large gyrencephalic brain with similar neuroanatomy to humans, longer lifespan of 12-15 years and other anatomical, physiological and metabolic similarities to humans [6].…”

“…In 2001, porcine mutant huntingtin (75Q) cDNA was microinjected in the pronucleus of fertilized eggs [3]. Several copies of the transgene were incorporated in the porcine genome, but there might have been problems with the gene intactness or transcriptional silencing.…”