RRC ID 12030
Author Takehashi M, Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Toyokuni S, Ogura A, Shinohara T.
Title Adenovirus-mediated gene delivery into mouse spermatogonial stem cells.
Journal Proc. Natl. Acad. Sci. U.S.A.
Abstract Spermatogonial stem cells represent a self-renewing population of spermatogonia, and continuous division of these cells supports spermatogenesis throughout the life of adult male animals. Previous attempts to introduce adenovirus vectors into spermatogenic cells, including spermatogonial stem cells, have failed to yield evidence of infection, suggesting that male germ cells may be resistant to adenovirus infection. In this study we show the feasibility of transducing spermatogonial stem cells by adenovirus vectors. When testis cells from ROSA26 Cre reporter mice were incubated in vitro with a Cre-expressing adenovirus vector, Cre-mediated recombination occurred at an efficiency of 49-76%, and the infected spermatogonial stem cells could reinitiate spermatogenesis after transplantation into seminiferous tubules of infertile recipient testes. No evidence of germ-line integration of adenovirus vector could be found in offspring from infected stem cells that underwent Cre-mediated recombination, which suggests that the adenovirus vector infected the cells but did not stably integrate into the germ line. Nevertheless, these results suggest that adenovirus may inadvertently integrate into the patient's germ line and indicate that there is no barrier to adenovirus infection in spermatogonial stem cells.
Volume 104(8)
Pages 2596-601
Published 2007-2-20
DOI 10.1073/pnas.0609282104
PII 0609282104
PMID 17299052
PMC PMC1815228
MeSH Adenoviridae / metabolism* Adenoviridae / physiology Animals Female Gene Deletion Gene Transfer Techniques* Humans Insemination Integrases / metabolism Male Mice Proteins / genetics RNA, Untranslated Recombination, Genetic Spermatogenesis Spermatogonia / cytology* Spermatogonia / metabolism* Spermatogonia / virology Stem Cells / cytology* Stem Cells / metabolism* Stem Cells / virology Virus Integration beta-Galactosidase / metabolism
IF 9.504
Times Cited 36
WOS Category REPRODUCTIVE BIOLOGY
Resource
DNA material AxCANLacZ (RDB03211) AxCANCre (RDB01748).