title: Male germline and embryonic stem cell lines from NOD mice: efficient derivation of GS cells from a nonpermissive strain for ES cell derivation.
abstract: The nonobese diabetic (NOD) mouse is a valuable model for human type 1 diabetes and the development of humanized mice. Although the importance of this mouse strain is widely recognized, its usefulness is constrained by the absence of NOD embryonic stem (ES) lines with adequate germline transmission competence. In the present study, we established two germline transmission-competent types of cell lines from NOD mice; these cell lines, male germline stem (GS) cells and ES cells, were derived from NOD spermatogonia and blastocysts, respectively. NOD-GS cells proliferated in vitro and differentiated into mature sperm after transplantation into testis. NOD-ES cell lines were effectively established from NOD blastocysts using culture medium containing inhibitors for fibroblast growth receptor, MEK, and GSK3. Both the NOD-GS and NOD-ES cell lines transmitted their haplotypes to progeny, revealing a novel strategy for gene modification in a pure NOD genetic background. Our results also suggest that the establishment of GS cells is an effective procedure in nonpermissive mouse strains or other species for ES cell derivation.
authors.affiliation: Laboratories for Genomic Reprogramming, Center for Developmental Biology, RIKEN, Kobe, Japan. ohta@cdb.riken.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Ohinata
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Yuka
authors.initials: Y
authors.lastname: Morioka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakaide
authors.forename: Mitinori
authors.initials: M
authors.lastname: Saitou
authors.forename: Osami
authors.initials: O
authors.lastname: Kanagawa
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Wakayama
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005838:Genotype; D007315:Insemination, Artificial; D008297:Male; D008745:Methylation; D051379:Mice; D016688:Mice, Inbred NOD; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology*; D033581:Stem Cell Transplantation