Genetic influences in mouse spermatogonial stem cell self-renewal.
Spermatogonial stem cells (SSCs) are slowly dividing cells that undergo self-renewal division to support spermatogenesis. Although the effects of genetic background in stem cell self-renewal have been well studied in hematopoietic stem cells, little is known about its effect on stem cells in other self-renewing tissues, including SSCs. To examine whether genetic factors are involved in regulation of SSC self-renewal, we first studied spermatogenesis in different inbred mouse strains (C57BL/6, DBA/2, AKR, BALB/C and C3H) after chemical damage caused by busulfan. Spermatogenesis in the DBA/2 and AKR strains was relatively resistant to busulfan treatment, whereas spermatogenesis was diminished in C57BL/6 mice and nearly ablated in C3H and BALB/C mice. Serial germ cell transplantation experiments provided functional evidence that SSCs with the DBA/2 background expanded more rapidly than those with the B6 background. Finally, we also employed the Germline Stem (GS) cell culture technique to examine the self-renewal activity in vitro. Although genetic manipulation of GS cells has been limited to those from the DBA/2 background, we produced transgenic offspring of the C3H background by electroporation of GS cells with a plasmid vector. Our results underscore the importance of genetic factors in SSC self-renewal. Furthermore, application of genetic modification techniques to GS cells with non-DBA/2 backgrounds extends the potential of a SSC-based approach in male germline modification.
Kanatsu-Shinohara
Mito
M
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Japan.
Ogonuki
Narumi
N
Miki
Hiromi
H
Inoue
Kimiko
K
Morimoto
Hiroko
H
Takashima
Seiji
S
Ogura
Atsuo
A
Shinohara
Takashi
T
D000818:Animals; D002066:Busulfan / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D005838:Genotype; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010641:Phenotype; D013091:Spermatogenesis / Q000235:genetics*; D013093:Spermatogonia / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
D002066:Busulfan