Establishment of a strain of F8 gene-targeted pigs (hemophilia-A pigs) by xenografting of fetal testicular tissue from neonatally moribund cloned pigs

2016 Fiscal Year Final Research Report

• Project/Area Number: 26292171
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: National Agriculture and Food Research Organization (2016); National Institute of Agrobiological Sciences (2014-2015)
• Principal Investigator: KANEKO Hiroyuki 国立研究開発法人農業・食品産業技術総合研究機構, 生物機能利用研究部門 動物機能利用研究領域, ユニット長 (60343993)
• Co-Investigator(Kenkyū-buntansha): 菊地 和弘 国立研究開発法人農業生物資源研究所, 動物発生分化研究ユニット, 上級研究員 (20360456) ; 中井 美智子 国立研究開発法人農業生物資源研究所, 医用モデルブタ研究開発ユニット, 任期付研究員 (30442825) ; 大西 彰 日本大学, 生物資源科学部, 教授 (30414890)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 血友病モデルブタ / 精巣異種間移植 / 超低温保存 / 系統樹立

Outline of Final Research Achievements

Our institute has developed a porcine model of hemophilia-A (hemophilia-A pig) by nuclear transfer cloning of fetal fibroblasts after disruption of the X-linked coagulation factor VIII (F8) gene. As a recessive disease, heterozygous female clones were expected to be asymptomatic, but died of severe bleeding as well as hemizygous male clones, thus making it impossible to obtain progeny of the hemophilia-A pigs. In this study, we tried to establish a strain of hemophilia-A pigs utilizing sperm recovered from testicular tissue of fetal hemizygous clones that had been grafted into nude mice. Two heterozygous pigs were generated: the pigs were asymptomatic and then delivered 5 hemizygous and 4 heterozygous piglets. Thus, testicular xenografting provides an opportunity to generate offspring from fetal hemizygous clones. Such heterozygous pigs avoid the discrepancy between genotype and phenotype in terms of F8, and will distribute progeny for the development of new therapeutics.

Free Research Field

家畜繁殖学