Electroporated transgene-rescued spermatogenesis in infertile mutant mice with a sertoli cell defect.
The molecular basis of most human male infertility arising from spermatogenesis disruption is poorly understood because of a lack of useful investigation systems. To study the roles of the supporting Sertoli cells in mammalian spermatogenesis, we improved an electroporation technique for seminiferous tubules in vivo. Because Sertoli cells barely proliferate in mature testis, linear transgenes are not incorporated into the genome and quickly degrade. However, circular expression vector is stably expressed in Sertoli cells for a long period. By electrotransformation of a complete cDNA, we rescued defective spermatogenesis in infertile Sl(17H)/Sl(17H) mutant mice with partial dysfunction of stem cell factor in Sertoli cells. Application of this gene transfer system will facilitate both the understanding of spermatogenesis and the development of new gene therapies for human male infertility.
Yomogida
Kentaro
K
Department of Science for Laboratory Animal Experimentation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Yagura
Yo
Y
Nishimune
Yoshitake
Y
D000199:Actins / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D004270:DNA, Circular / Q000235:genetics; D018274:Electroporation; D015870:Gene Expression; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins; D007248:Infertility, Male / Q000235:genetics* / Q000628:therapy; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012671:Seminiferous Tubules / Q000166:cytology; D012708:Sertoli Cells / Q000378:metabolism*; D013076:Sperm Count; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000166:cytology; D019089:Stem Cell Factor / Q000235:genetics; D014162:Transfection / Q000379:methods*
D000199:Actins; D004270:DNA, Circular; D008164:Luminescent Proteins; D019089:Stem Cell Factor; D049452:Green Fluorescent Proteins