| Autor: |
Satoshi Watanabe, Mito Kanatsu-Shinohara, Narumi Ogonuki, Shogo Matoba, Atsuo Ogura, Takashi Shinohara |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, Vol 10, Iss 5, Pp 1551-1564 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2213-6711 |
| DOI: |
10.1016/j.stemcr.2018.03.005 |
| Popis: |
Summary: Adeno-associated virus (AAV) penetrates the blood-brain barrier, but it is unknown whether AAV penetrates other tight junctions. Genetic manipulation of testis has been hampered by the basement membrane of seminiferous tubules and the blood-testis barrier (BTB), which forms between Sertoli cells and divides the tubules into basal and adluminal compartments. Here, we demonstrate in vivo genetic manipulation of spermatogonial stem cells (SSCs) and their microenvironment via AAV1/9. AAV1/9 microinjected into the seminiferous tubules penetrated both the basement membrane and BTB, thereby transducing not only Sertoli cells and SSCs but also peritubular cells and Leydig cells. Moreover, when congenitally infertile KitlSl/KitlSl-d mouse testes with defective Sertoli cells received Kitl-expressing AAVs, spermatogenesis regenerated and offspring were produced. None of the offspring contained the AAV genome. Thus, AAV1/9 allows efficient germline and niche manipulation by penetrating the BTB and basement membrane, providing a promising strategy for the development of gene therapies for reproductive defects. : In this article, Shinohara and colleagues show the feasibility of adeno-associated virus (AAV) to penetrate the blood-testis barrier and the basal membrane of the seminiferous tubules of mouse testes. AAVs infected not only germ cells but also their microenvironment. The technique was used to rescue a mouse model of infertility with Sertoli cell defect. Keywords: adeno-associated virus, blood-testis barrier, Sertoli cells, spermatogonia, spermatogenesis |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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