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2023 Fiscal Year Final Research Report

Development of spermatogonial stem cell xenotransplantation method using transgenic nude mice

Research Project

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Project/Area Number 20K06462
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionKitasato University

Principal Investigator

Kakiuchi Kazue  北里大学, 獣医学部, 助教 (90509184)

Co-Investigator(Kenkyū-buntansha) 高岸 聖彦  北里大学, 獣医学部, 講師 (20216633)
久保田 浩司  北里大学, 獣医学部, 教授 (80263094)
Project Period (FY) 2020-04-01 – 2024-03-31
Keywords精原幹細胞 / 異種移植 / 精子形成
Outline of Final Research Achievements

In this study, we aimed to establish a xenotransplantation method that focuses on the species-specificity of differentiation-inducing factors for spermatogonial stem cells. Using pigs as a model, we created transgenic mice that express differentiation factors derived from the donor animal species, and we attempted to continuously reconstruct spermatogenesis derived from other animal species by xenotransplantation of stem cells. Since abnormalities such as alopecia and pigmentation have been reported in mice overexpressing differentiation factors, we attempted to express them downstream of a promoter that functions only in Sertoli cells. We found that the Rhoxb5 promoter, a Sertoli cell marker protein, functions stably in sexually mature mouse testes and Sertoli cell lines, and created transgenic nude mice that express a pig-derived differentiation factor downstream of this promoter.

Free Research Field

精原幹細胞

Academic Significance and Societal Importance of the Research Achievements

精原幹細胞は、自己複製して雄個体の生涯の精子形成を維持することから、遺伝情報を継ぐことができる成体に存在する唯一の幹細胞として知られている。不妊マウス精巣の精細管内移植による精子形成の再構築により、幹細胞活性の測定ツールが確立されている。非げっ歯類である動物種の精原幹細胞株の樹立は、優良家畜や希少動物の種の保存に貢献するだけでなく、ヒトの男性不妊治療へも応用が期待できるが、不妊レシピエント雄個体の作製が困難なため継続的な精子形成を立証することができずに研究の妨げになっている。本研究課題は、研究室レベルで非げっ歯類動物種由来の精原幹細胞活性を測定するツールを提供できる可能性を示す。

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Published: 2025-01-30  

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