title: A novel Amh-Treck transgenic mouse line allows toxin-dependent loss of supporting cells in gonads.
abstract: Cell ablation technology is useful for studying specific cell lineages in a developing organ in vivo. Herein, we established a novel anti-Müllerian hormone (AMH)-toxin receptor-mediated cell knockout (Treck) mouse line, in which the diphtheria toxin (DT) receptor was specifically activated in Sertoli and granulosa cells in postnatal testes and ovaries respectively. In the postnatal testes of Amh-Treck transgenic (Tg) male mice, DT injection induced a specific loss of the Sertoli cells in a dose-dependent manner, as well as the specific degeneration of granulosa cells in the primary and secondary follicles caused by DT injection in Tg females. In the testes with depletion of Sertoli cell, germ cells appeared to survive for only several days after DT treatment and rapidly underwent cell degeneration, which led to the accumulation of a large amount of cell debris within the seminiferous tubules by day 10 after DT treatment. Transplantation of exogenous healthy Sertoli cells following DT treatment rescued the germ cell loss in the transplantation sites of the seminiferous epithelia, leading to a partial recovery of the spermatogenesis. These results provide not only in vivo evidence of the crucial role of Sertoli cells in the maintenance of germ cells, but also show that the Amh-Treck Tg line is a useful in vivo model of the function of the supporting cell lineage in developing mammalian gonads.
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Mai
authors.initials: M
authors.lastname: Shinomura
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Kasane
authors.initials: K
authors.lastname: Kishi
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tomita
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Miyuri
authors.initials: M
authors.lastname: Kawasumi
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kanezashi
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsunekawa
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Aisa
authors.initials: A
authors.lastname: Ozawa
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Aiyama
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Asuka
authors.initials: A
authors.lastname: Yoneda
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Michiko
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Picard
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kurohmaru
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France.
authors.forename: Masami
authors.initials: M
authors.lastname: Kanai-Azuma
authors.affiliation: Department of Veterinary AnatomyThe University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Experimental Animal Model for Human DiseaseCenter for Experimental Animals, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, JapanGraduate School of Biological SciencesNara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, JapanINSERM U1133BFA, University Paris VII, 75205 Paris Cedex 13, France aykanai@mail.ecc.u-tokyo.ac.jp.
authors.forename: Yoshiakira
authors.initials: Y
authors.lastname: Kanai
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation; D004167:Diphtheria Toxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects*; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D010053:Ovary / Q000166:cytology*; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects*; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000166:cytology*
chemical_list: D004167:Diphtheria Toxin; D066257:Heparin-binding EGF-like Growth Factor; D054304:Anti-Mullerian Hormone