(Re)producing transgenic pigs for xenotransplantation

Auteurs

• Andrea Bahr

Paramètres

• Santé & Médecine

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Xenotransplantation presents a potential solution for end-stage organ failure, with pigs identified as viable donor species. However, genetic modifications are essential to address the incompatibilities between human and porcine immune systems. While there is extensive experience in breeding multi-transgenic mice for biomedical research, breeding multi-transgenic pigs poses unique challenges. Key limitations include: (i) inbreeding negatively impacts fertility and litter size in pigs, whereas congenic mouse strains face fewer restrictions; (ii) pigs have longer generation times of about 12 months and pregnancies lasting 115 days, necessitating meticulous breeding management; (iii) the costs and space needed for pig maintenance are significantly higher than for mice. Additionally, understanding xenograft rejection mechanisms remains limited, indicating that more transgenes or novel combinations may be necessary in the future. This thesis outlines the establishment of multi-transgenic GalKO/CD46/HLA-E and GalKO/CD46/hTM donor herds, as well as the characterization of new hTM and LEA29Y transgenic lines for future breeding. Initial steps included selecting two fertile GalKO/CD46 boars and three fertile HLA-E sows as founders for the GalKO/CD46/HLA-E breeding herd, with plans to incorporate additional xeno-relevant transgenes. Breeding schedules were developed to balance inbreeding, transgene segregation, and time requirements, id

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• Année de publication: 2011