Phenotypic Analyses and Identification of Causal Mutations In Medaka Mutants with Gonadal Dysgenesis.

• Project/Area Number: 17370083
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: National Institute for Basic Biology
• Principal Investigator: TANAKA Minoru National Institute for Basic Biology, Lab. of Molecular Genetics for Reproduction, Associate Professor, 生殖遺伝学研究室, 准教授 (80202175)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥12,700,000 (Direct Cost: ¥12,700,000); Fiscal Year 2006: ¥6,100,000 (Direct Cost: ¥6,100,000); Fiscal Year 2005: ¥6,600,000 (Direct Cost: ¥6,600,000)
• Keywords: SEX DIFFERENTIATION / GONAD / MUTANT / MEDAKA / AMH / CELL LINEAGE / PHENOTYPE / SEX REVERSAL / マッピング / 卵巣

Research Abstract

Before analysis of the mutants displaying defects in gonadogenesis, the cell lineages that constitute the gonad have been characterized in terms of the motility, origin and translational regulation. Then, phenotypic analyses and identification of the mutations have been performed for the mutant medaka.
Mutant medaka, totoro (tot), was identified as medaka showing a hypertrophic gonad. Phenotypic analyses showed that tot possessed an excessive number of germ cells and a half of genetic male exhibited male-to-female sex reversal. A mutation was found in the kinase domain of anti-Mullerian hormone receptor type II, resulting in tyrosine to cysteine substitution. This gene has been known to be involved in sex-specific development of accessory organs found in only mammals and function in other vertebrates remained to be elucidated. Our result indicated that this gene is involved in proliferation of germ cells in a sex-dependent manner. Since sex-reversal was speculated to be due to a result of a burst number of germ cells, medaka with the complete loss of germ cells were generated. The germ-cell deficient medaka displayed a female-male sex reversal, suggesting that germ cells are deeply committed to sexual dimorphic gonadogenesis.
A mutation of zenzai mutant has also been identified in one of the surface antigen genes. In vivo germ cell-tracing analysis indicated that two types of proliferation are present in the gonads and the process of proliferation involved in germ cell maintenance was affected in this mutant, which brings about sterility in adult stage.

Research Products

• [Journal Article] The totoro mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and development (2007)
  • Author(s): Morinaga C. et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sox9b/sox9a2-EGFP transgenic medaka reveals the orphological reorganization of the gonads and a common presursor of both the female and male supporting cells. (2007)
  • Author(s): Nakamura S. et al.
  • Journal Title: Mol. Reprod. Dev. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Duplicated Abd-B class genes in medaka hoxAa and hoxAb clusters exhibit different expression patterns in pectoral fin buds (2007)
  • Author(s): Takamautsu N. et al.
  • Journal Title: Dev. Genes Evol. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The totoro-mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and sexual development. (2007)
  • Author(s): Morinaga, C., Saito, D., Nakamura, S., Sasaki, T., Asakawa, S., Shimizu, N., Mitani, H., Furutani-Seiki, M., Tanaka, M (corresponding author)., Kondoh, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sox9b/sox9a2-EGFP transgenic medaka reveals the morphological reorganization of the gonads and a common presursor of both the female and male supporting cells. (2007)
  • Author(s): Nakamura, S., Aoki, Y., Saito, D., Kuroki, Y., Fujiyama, A., Naruse, K., Tanaka, M.
  • Journal Title: Mol. Reprod. Dev.
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Duplicated Abd-B class genes in medaka hoxAa and hoxAb clusters exhibit different expression patterns in pectoral fin buds (2007)
  • Author(s): Takamatsu, N., Kurosawa, G., Takahashi, M., Inokuma, R., Tanaka, M., Kanamori, A., Hori, H.
  • Journal Title: Dev. Genes Evol.
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sox9b/sox9a2-EGFP transgenic medaka reveals the morphological reorganization of the gonads and a common presursor of both the female and male supporting cells. (2007)
  • Author(s): Nakamura S. et al.
  • Journal Title: Mol. Reprod. Dev. (印刷中)
• [Journal Article] The totoro mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and sexual development. (2007)
  • Author(s): Morinaga C. et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA. (印刷中)
• [Journal Article] Visualization of primordial germ cells in vivo using GFP-nosl 3'UTR mRNA. (2006)
  • Author(s): Saito T. et al.
  • Journal Title: Int. J. Dev. Biol. 51 Pages: 691-700
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Time-lapse analysis reveals different modes of primordial germ cell migration in the medaka Oryzlas latipes. (2006)
  • Author(s): Kurokawa H. et al.
  • Journal Title: Develop. Growth Differ. 48 Pages: 209-221
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Quantitative bioimaging analysis of gonads in olvas-GFP/ST-II YI medaka (transgenic Oryzias latipes) exposed to ethinylestradiol. (2006)
  • Author(s): Hano, T., Oshima, Y., Kinoshita, M., Tanaka, M., Mishima, N., Ohyama, N., Yanagawa, T., Wakamatsu, Y., Ozato, K., Honjo, T.
  • Journal Title: Int. J. Dev. Biol 50 Pages: 691-700
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification and lineage tracing of two populations of somatic gonadal precursors in medaka embryos. (2006)
  • Author(s): Nakamura, S,.Kobayashi, D., Aoki, Y., Yokoi, H., Ebe, Y., Wittbrodt, J, Tanaka, M.
  • Journal Title: Dev. Biol. 295 Pages: 678-688
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Time-lapse analysis reveals different modes of primordial germ cell migration in the medaka Oryzias latipes. (2006)
  • Author(s): Kurokawa, H., Aoki, Y., Nakamura, S., Ebe, Y., Kobayashi, D, Tanaka, M.
  • Journal Title: Develop. Growth Differ. 48 Pages: 209-221
  • NAID: 10018123319
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification and lineage tracing of two population of somatic gonadal precursors in medaka embryos. (2006)
  • Author(s): Nakamura S. et al.
  • Journal Title: Dev. Biol. 295 Pages: 678-688
• [Journal Article] Visualization of primordial germ cells in vivo using GFP-nos1 3'UTR mRNA (2006)
  • Author(s): Saito T. et al.
  • Journal Title: Int. J. Dev. Biol. 51 Pages: 691-700
• [Journal Article] Time-lapse analysis reveals different modes of primordial germ cell migration in the medaka Oryzias latipes. (2006)
  • Author(s): Kurokawa H. et al.
  • Journal Title: Develop. Growth Differ. 48 Pages: 209-211
• [Journal Article] Quantitative Bio-imaging analysis for evaluation of sexual differentiation in germ cells of o/vas-GFP/STII YI medaka (Oryzias latipes) nanoinjected in ovo with ethinylestradiol. (2005)
  • Author(s): Hano, T., Oshima, Y., Oe, T., Kinoshita, M., Tanaka, M., Wakamatsu, Y., Ozato, K., Honjo, T.
  • Journal Title: Environ. Toxicol. Chem. 24 Pages: 70-77
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification and lineage tracing of two population of somatic gonadal precursors in medaka embryos.
  • Author(s): Nakamura S. et al.
  • Journal Title: Dev. Biol.
  • Description: 「研究成果報告書概要(和文)」より