RRC ID 50638
Author Watanabe S, Kanatsu-Shinohara M, Ogonuki N, Matoba S, Ogura A, Shinohara T.
Title In Vivo Genetic Manipulation of Spermatogonial Stem Cells and Their Microenvironment by Adeno-Associated Viruses.
Journal Stem Cell Reports
Abstract 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.
Volume 10(5)
Pages 1551-1564
Published 2018-5-8
DOI 10.1016/j.stemcr.2018.03.005
PII S2213-6711(18)30132-2
PMID 29628393
PMC PMC5995272
MeSH Animals Cellular Microenvironment* Dependovirus / metabolism* Genetic Techniques* Infertility, Male / pathology Kinetics Male Mice, Inbred C57BL Microinjections Neuraminidase / metabolism Serogroup Sertoli Cells / pathology Spermatogenesis Spermatogonia / cytology* Spermatogonia / metabolism Spermatozoa / cytology Stem Cell Factor / metabolism Stem Cells / cytology* Stem Cells / metabolism Testis / cytology
IF 6.032
Times Cited 8
DNA material AxCANCre (RDB01748)