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Exo utero gene introduction to specific organs and tissues during fetal and neonatal period

Research Project

Project/Area Number 07507007
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Embryonic/Neonatal medicine
Research InstitutionShimane Medical University

Principal Investigator

OTANI Hiroki  Shimane Medical University, Department of Anatomy, Professor, 医学部, 教授 (20160533)

Co-Investigator(Kenkyū-buntansha) TATEWAKI Reiko  Shimane Medical University, Department of Biology, Instructor, 医学部, 助手 (10112129)
NAORA Hiroyuki  Shimane Women's College, Department of Food Science, Instructor, 家政科, 助手 (70222156)
HASHIMOTO Ryuju  Shimane Medical University, Department of Anatomy, Instructor, 医学部, 助手 (90252907)
HATTA Toshihisa  Shimane Medical University, Department of Anatomy, Instructor, 医学部, 助手 (20238025)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1997: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1996: ¥5,100,000 (Direct Cost: ¥5,100,000)
Keywordsexo utero development / gene introduction / liposome / electroporation / antisense oligonucleotide / histogenesis / アンチセンスオリゴ / マウス胎児 / in situ hybridization / 免疫組織化学 / 子宮外発生
Research Abstract

Exo utero development system and techniques of microinjection into fetuses have been improved. To increase efficiency of the uptake of exogenous genes injected into mouse embyonic organs, optimal conditions of gene carriers and electroporation have been established, and usefulness of antisense oligonucleotides has been estimated. To demonstrate the potential of exo utero system, several biologically active substances were injected into the specific fetal organs, and their effects were analyzed. The exo utero experimental systems to analyze the histogenesis of several organs have been established.
1. Improvement of exo utero system : Reduction of manipulation time for each procedure, modification of incision of the uterine wall, anesthesia and resuscitation, all together have significantly improved the survival rate after the manipulation and efficiency of microinjection.
2. Optimization of conditions for gene introduction : Among several liposomes, the ones with the highest efficiency of … More reporter gene incorporation under different conditions were determined. Conditions of electroporation with the BTX system were evaluated and the flat type electrode showed an excellent handling. Conditions have been established for good diffusion of injected solution into the cerebral parenchyme with minimum damage to the tissue.
3. Introduction of antisense oligonucleotides : Antisense oligonucleotides for Tag1 and Mab21 was injected into the fetal cerebral ventricle at single-dose or double-dose with an interval, and the protein expression levels decreased significantly.
4. Application of exo utero system into the functional analysis of regulatory molecules in the histogenesis of the organs : LIF was injected into the cerebral ventricle and showed specific effects on the cerebral cortex including increase in the neuroblasts and fibers in the specific cortical layrs. The effects of ACTH on the fetal adrenal were similarly evidenced by the established exo utero experimental system. The exo utero experimental systems for analysis of pathogenesis of hydrocephaly and excencephaly, and development of the inner ear and joints have also been established. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (75 results)

All Other

All Publications (75 results)

  • [Publications] H.Matsui: "The effects of PSK,a biological response modifier,on congenital ocular abnormalities induced by X-ray irradiation." Histol.Histopathol.10. 47-54 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Tatewaki: "Relationship between associations of NOR and chromosomal anomalies in the abnormal embryos of the diabetic and STZ-diabetic mouse." Biol. Neonate. 67. 132-139 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Otani: "Vestibulocochlear defects and effects of deuterium oxide in mutant bustling (BUS) mice." Acta Otolaryngol.(Stockholm). Suppl.519. 286-293 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Tamura: "Opaque eyes developed in transgenic mice with T-cell receptor δ Gene." Invest.Ophthalmol.Vis.Sci.36. 467-477 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Sato: "Hypertrophy of the preputial gland in transgenic mice expressing BCF/22 kDa extracellular matrix protein/dermatopontin cDNA." Transgenics. 1. 525-534 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Toyama: "The LIM class homeobox gene lim5 : Implied role in CNS patterning in Xenopus and zebrafish." Dev.Biol.170. 583-593 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hashimoto: "Histocytochemical and immunohistochemical studies related to the role of glycogen in human developing digestive organs." Anat.Embryol.192. 497-505 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Moriyama: "Occurrence of craniofacial anomalies and liver tumor in transgenic mice expressing osteoblast-specific factor-1 (OSF-1) gene." Transgenics. 2. 69-78 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Hatta: "In vivo analysis of RGD-sequence dependent cortical histogenesis in mouse telencephalon." Shimane J.Med.Sci.14. 1-6 (1995, 1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] J.Udagawa: "Effects of deuterium oxide on the hair growth." J.Deuterium Sci.5. 15-21 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Oguni: "Immunohistochemical study of 28-kD heat shock protein in the lens of young human embryos." Ophthalmic Res.28. 270-274 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Moriyama: "Degenerative hairlets on the vestibular sensory cells in mutant bustling (BUS/Idr) mice." Acta Otolaryngol.(Stockh). 117. 20-24 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 大谷 浩: "マウス・ラットの解剖と器官発生." 小児外科. 29. 143-152 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Hashimoto: "Selective translocation of different markers in the ante- and retrograde pathwaya between the Golgi apparatus and the rough endoplasmic reticulum in a hybridoma cell line." Ann.Anat.179. 105-116 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Sekimoto: "Developmental analysis of chlorambucil-induced occipital bleds in mice." Cong.Anom.37. 31-45 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 大谷 浩: "個体発生における遺伝子の働きと環境による修飾." 島根医学. 17. 10-19 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] J.Hatta: "Experimental hydrocephalus : history of animal models and the application of deuterium oxide to treatment." Jpn.J.Deuterium Sci.6. 13-19 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Koera: "K-ras is essential for the development of the mouse embryo." Oncogene. 15. 1151-1159 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Matsuda: "Apoptosis in the development of the temporomandibular joint." Anat.Embryol.196. 383-391 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Omori: "Deuterium oxide (heavy water) accelerates actin assembly in vitro and changes microfilament distribution in cultured cells." Eur.J.Cell Biol.74. 273-280 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 大谷 浩: "初期発生:卵割から胚葉形成まで" 生体の科学. 49. 54-61 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Oishi: "A novel Drosophila nuclear protein serine/threonine kinase implicated in germ line establishment." Mechanism of Development. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Kihara: "Development of the hip joint in human embryos and fetuses." Shimane J.Med.Sci.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Zhang: "Induction of ectopic corticotrophictumor in mouse embryos by exoutero cell transplantation and its effects on the fetal adrenal gland." Endocrinology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 森山 賢治: "ノックアウトマウスデータブック(Molecular Medicinc 臨時増刊)" 中山書店, 564 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Oishi: "Kinases andphosphatases in lymphocyte and neuronal signaling" Springer, 368 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Matsui: "The effects of PSK,a biological response modifier, on congenital ocular abnormalities induced by X-ray irradiation." Histol.Histopathol.10. 47-54 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Tatewaki: "Relationship between associations of NOR and chromosomal anomalies in the abnormal embryos of the diabetic and STZ-diabetic mouse." Biol.Neonate. 67. 132-139 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Otani: "Vestibulocochlear defects and effects of deuterium oxide in mutant bustling (BUS) mice." Acta Otolaryngol. (Stockholm). Suppl.519. 286-293 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Tamura: "Opaque eyes developed in transgenic mice with T-cell receptor d Gene." Invest.Ophthalmol.Vis.Sci.36. 467-477 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Sato: "hypertrophy of the preputial gland in transgenic mice expressing BCF/22 kDa extracellular matrix protein/dermatopontin cDNA." Transgenics. 1. 525-534 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Toyama: "The LIM class homeobox gene lim5 : Implied role in CNS patterning in Xenopus and zebrafish." Dev.Biol.170. 583-593 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hashimoto: "Histocytochemical and immunohistochemical studies related to the role of glycogen in human developing digestive organs." Anat.Embryol.192. 497-505 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Moriyama: "Occurrence of craniofacial anomalies and liver tumor in transgenic mice expressing osteoblast-specific factor-1 (OSF-1) gene." Transgenics. 2. 69-78 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Hatta: "In vivo analysis of RGD-sequence dependent cortical histogenesis in mouse telencephalon." Shimane J.Med.Sci.14. 1-6 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] J.Udagawa: "Effects of deuterium oxide on the hair growth." J.Deuterium Sci.5. 15-21 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Oguni: "Immunohistochemical study of 28-kD heat shock protein in the lens of young human embryos." Ophthalmic Res.28. 270-274 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Moriyama: "Degenerative hairlets on the vestibular sensory cells in mutant bustling (BUS/Idr) mice." Acta Otolaryngol. (Stockh). 117. 20-24 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] R.Hashimoto: "Selective translocation of different markers in the ante- and retrograde pathways between the Golgi apparatus and the rough endoplasmic reticulum in a hybridoma cell line." Ann.Anat.179. 105-116 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Sekimoto: "Developmental analysis of chlorambucil-induced occipital bleds in mice." Cong.Anom.37. 31-45 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] J.Hatta: "Experimental hydrocephalus : history of animal models and the application of deuterium oxide to treatment." Jpn.J.Deuterium Sci.6. 13-19 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Kocra: "K-ras is essential for the development of the mouse embryo." Oncogene. 15. 1151-1159 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Matsuda: "Apoptosis in the development of the temporomandibular joint." Anat.Embryol.196. 383-391 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Omori: "Deuterium oxide (heavy water) accelerates actin assembly in vitro and changes microfilament distribution in cultured cells." Eur.J.Cell Biol.74. 273-280 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Oishi: "A novel Drosophila nuclear protein serine/threonine kinase implicated in germ line establishment." Mechanism of Development. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Kihara: "Development of the hip joint in human embryos and fetuses." Shimane J.Med.Sci.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Zhang: "Induction of ectopic corticotrophic tumor in mouse embryos by exo utero cell transplantation and its effects on the fetal adrenal gland." Endocrinology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Oishi: Kinases and phosphatases in lymphocyte and neuronal signaling. Springer, (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hatta,J.: "Experimantal hydrocephalus : history of animal models and the application of deuterium oxide to treatment." Jpn.J.Deuterium Sci.6. 13-19 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sekimoto,H.: "Developmental analysis of chlorambucil-induced occipital bleds in mice." Cong.Anom.37. 31-45 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koera,K.: "K-ras in essential for the development of the mouse embryo." Oncogene. 15. 1151-1159 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsuda,S.: "Apoptosis in the development of the temporomandibular joint." Anat.Embryol.196. 383-391 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Omori,H.: "Deuterium oxide(heavy water)accelerates actin assembly in vitro and changes microfilament distribution in cultured cells." Eur.J.Cell Biol.74. 273-280 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大谷 浩: "初期発生:卵割から胚葉形成まで." 生体の科学. 49. 54-61 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oishi,I.: "A novel Drosophila nuclear protein serine/threonine kinase implicated in germ line establishment." Mechanism of Development. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Kihara,I.: "Development of the hip joint in human embryos and fetuses." Shimane J.Med.Sci.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Zhang,H.: "Induction of ectopic corticotrophic tumor in mouse embryos by exo utero cell transplantation and its effects on the fetal adrenal gland." Endocrinology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 森山賢治: "ノックアウトマウスデータブック(Molecular Medicine臨時増刊)" 中山書店, 564 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oishi,I.: "Kinases andphosphatases in lymphocyte and neuronal signaling" Springer, 358 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hashimoto,R.: "Selective translocation of different markers in the ante-and retrograde pathways between the Golgi apparatus and the rough endoplasmic reticulum in a hybridoma cell line." Ann.Anat.179 (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sekimoto,H.: "Developmental analysis of chlorambucil-induced occipital bleds in mice." Cong.Anom.37 (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 大谷 浩: "マウス・ラットの解剖と器官発生." 小児外科. 29. 143-152 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Moriyama,K.: "Degenerative hairlets on the vestibular sensory cells in mutant bustling (BUS/Idr) mice." Acta Otolaryngol.(Stockh). 117. 20-24 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oguni,M.: "Immunohistochemical study of 28-kD heat shock protein in the lens of young human embryos." Ophthalmic Res.28. 270-274 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Moriyama,K.: "Occurrence of craniofacial anomalies and liver tumor in transgenic mice expressing osteoblast-specific factor-1 (OSF-1) gene." Transgenics. 2. 69-78 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Udagawa,J.: "Effects of deuterium oxide on the hair growth." J.Deuterium Sci.5. 15-21 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hatta,T.: "In vivo analysis of RGD-sequence dependent cortical histogenesis in mouse telencephalon." Shimane J.Med.Sci.14. 1-6 (1995/96)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Matsui: "The effects of PSK,a biological rasponse modifier,on congenital ocular abnormalities induced by X-ray irradiation." Histol.Histopathol.10. 47-54 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Reiko Tatewaki: "A relationship between associations of NORs and chromosomal anomalies in the abnormal embryos of the diabetic NOD and STZ-diabetic mouse." Biol.Neonate. 67. 132-139 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Otani: "Vestibulocochlear defects and effects of deuterium oxide in mutant bustling (BUS) mice." Acta Oto-Laryngol. (Stockholm). Suppl.519. 286-293 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Haruko Tamura: "Opaque eyes developed in transgenic mice with T-cell receptor δ Gene." Invest. Ophthalmol. Vis.Sci.36. 467-477 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M.Sato: "Hypertrophy of the preputial gland in transgenic mice expressing BCF/22 kDa extracelluar matrix protein/dematopontin cDNA." Transgenics. 1. 525-534 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Reiko Toyama: "The LIM Class Homeobox Gene lim5 : Implied Role in CNS Patterning in Xenopus and Zebrafish." Dev.Biol.170. 583-593 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Koji Hashimoto: "Histocytochemical and immunohistochemical studies related to the role of glycogen in human developing digestive organs." Anat.Embryol.192. 497-505 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Moriyama,K.: "Occurrence of craniofacial anomalies and liver tumor in transgenic mice expressing osteoblast-specific factor-1 (OSF-1) gene." Transgenics. (in press).

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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