Restoration of spermatogenesis by lentiviral gene transfer: Offspring from infertile mice

Ikawa, Masahito; Tergaonkar, Vinay; Ogura, Atsuo; Ogonuki, Narumi; Inoue, Kimiko; Verma, Inder M.

doi:10.1073/pnas.072207299

Cited by 118 publications

(103 citation statements)

References 37 publications

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“…This method is theoretically attractive but the efficiency of Sertoli cell transplantation is low, which is a technical hurdle of this method. The third method used a genetherapy strategy to introduce the Steel gene into the defective Sertoli cells of Sl/Sl d mice by adeno-or lenti-viral transductions 32,33 . This method also proved effective to produce fertile sperm in the testes of Sl/Sl d mice.…”

Section: Discussionmentioning

confidence: 99%

In vitro production of fertile sperm from murine spermatogonial stem cell lines

et al. 2011

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spermatogonial stem cells (ssCs) are the only stem cells in the body that transmit genetic information to the next generation. The long-term propagation of rodent ssCs is now possible in vitro, and their genetic modification is feasible. However, their differentiation into sperm is possible only under in vivo conditions. Here we show a new in vitro system that can induce full spermatogenesis from ssC lines or any isolated ssCs. The method depends on an organ culture system onto which ssCs are transplanted. The settled ssCs form colonies and differentiate up into sperm. The resultant haploid cells are fertile, and give rise to healthy offspring through micro-insemination. In addition, the system can induce spermatogenesis from ssCs that show spermatogenic failure due to a micro-environmental defect in their original testes. Thus, an in vitro system is established that can be used to correct or manipulate the micro-environmental conditions required for proper spermatogenesis from murine ssC lines.

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Section: Discussionmentioning

confidence: 99%

In vitro production of fertile sperm from murine spermatogonial stem cell lines

et al. 2011

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“…S4D). Two studies using adenovirus and lentivirus succeeded in making Sertoli cells of Sl/Sl d mice produce mKITL, thereby inducing spermatogenesis in their testes (22,23). This strategy appears more realistic for clinical application than the first two.…”

Section: Discussionmentioning

confidence: 99%

Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice

Sato

Yokonishi

Komeya

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Male infertility is most commonly caused by spermatogenic defects or insufficiencies, the majority of which are as yet cureless. Recently, we succeeded in cultivating mouse testicular tissues for producing fertile sperm from spermatogonial stem cells. Here, we show that one of the most severe types of spermatogenic defect mutant can be treated by the culture method without any genetic manipulations. The Sl/Sl d mouse is used as a model of such male infertility. The testis of the Sl/Sl d mouse has only primitive spermatogonia as germ cells, lacking any sign of spermatogenesis owing to mutations of the c-kit ligand (KITL) gene that cause the loss of membrane-bound-type KITL from the surface of Sertoli cells. To compensate for the deficit, we cultured testis tissues of Sl/Sl d mice with a medium containing recombinant KITL and found that it induced the differentiation of spermatogonia up to the end of meiosis. We further discovered that colony stimulating factor-1 (CSF-1) enhances the effect of KITL and promotes spermatogenesis up to the production of sperm. Microinsemination of haploid cells resulted in delivery of healthy offspring. This study demonstrated that spermatogenic impairments can be treated in vitro with the supplementation of certain factors or substances that are insufficient in the original testes.

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“…Additionally, the possibility Cell-type-specific lentivirus in brain JP Chhatwal et al exists for using these same vectors to achieve virally mediated transgenesis of oocytes or spermatogonia. 16,17 In addition to these applications, cell-type-selective viral vectors could potentially be used to generate regionspecific, cell-type-selective expression of desired transgenes, as well as region-specific, cell-type-selective, post-developmental knockout of floxed genes. The identification of a functioning CCK mini-promoter will be quite useful for studies aimed at understanding the function of the CCK sub-population of interneurons 10,18 within cortical and subcortical regions.…”

Section: Discussionmentioning

confidence: 99%

Identification of cell-type-specific promoters within the brain using lentiviral vectors

et al. 2007

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The development of cell-type-specific mini-promoters for genetic studies is complicated by a number of issues. Here, we describe a general method for the relatively rapid screening of specific promoter activity in cell culture, in acute brain slice preparations and in vivo. Specifically, we examine the activity of an B3 kb promoter region from the neuroactive peptide cholecystokinin (CCK) compared to the commonly used cytomegalovirus promoter. We find a high degree of cell-type selectivity in vivo using lentiviral approaches in rats and traditional transgenic approaches in mice. Appropriate colocalization of Cre-recombinase and CCK gene expression is found within the hippocampus, when the CCK promoter is driving either the expression of Cre-recombinase or green fluorescent protein. We also demonstrate fluorescent identification of CCK-positive interneurons that allows for cell-type-specific electrophysiologic studies in rats and mice. In conclusion, these studies identify a functional mini-promoter for the CCK gene and outline a novel and sensitive general method to test activity of selective promoters in vitro and in vivo. This approach may allow for the more rapid identification of specific promoters for use with transgenic animals, in genetically modified viruses, and in the design of targeted, therapeutic genedelivery systems.

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Restoration of spermatogenesis by lentiviral gene transfer: Offspring from infertile mice

Cited by 118 publications

References 37 publications

In vitro production of fertile sperm from murine spermatogonial stem cell lines

In vitro production of fertile sperm from murine spermatogonial stem cell lines

Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice

Identification of cell-type-specific promoters within the brain using lentiviral vectors

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