1990 Fiscal Year Annual Research Report

外来遺伝子DNA導入による新しいモデル動物の開発

Research Project

Project/Area Number	02206102
Research Institution	Tokai University
Principal Investigator	勝木元也東海大学, 医学部, 教授 (20051732)
Co-Investigator(Kenkyū-buntansha)	森正敬熊本大学, 遺伝研究所, 教授 (40009650) 鎌滝哲也北海道大学, 薬学部, 教授 (00009177) 近藤寿人名古屋大学, 理学部, 教授 (70127083) 山村研一熊本大学, 遺伝研究所, 教授 (90115197) 岩倉洋一郎東京大学, 医科学研究所, 助教授 (10089120)
Keywords	トランスジェニックマウス / 家族性アミロイドニュ-ロパシ- / 高血圧症モデル / ジ-ンタ-ゲッティング法 / 生物機能モデル / ヒト疾患モデル
Research Abstract	〔研究目的〕本研究は,ヒトDNAを主とする外来遺伝子DNAの初期胚への導入を通してバイオサイエンスの基礎として重要な生物機能モデルおよびヒト疾患モデル動物を開発することを目的とする。〔研究成果〕本年度は次のような成果をあげることができた。 1.家族性アミロイドニュ-ロパシ-(FAP)の原因突然変異遺伝子導入マウスを作成し,アミロイドの沈着を認め疾患モデルが確立した。 2.レニンおよびアンジオテンシノ-ゲン遺伝子導入マウスを作成したところ,両方の遺伝子をもつマウスのみ高血圧症を示した。このマウスはカプトプソルの投与により正常血圧に戻った。また,高血圧マウスは6ケ月内に半数次上が突然死した。以上のことから,原因が明確な高血圧症の動物実験系が確立したと考えられる。 3.エイズウィルスや急性白血病ウィルス遺伝子導入マウスを作成した。様々な症状を呈するマウスが得られたが,遺伝子発現との関係を現在検討中である。 4.その他,多数のヒト遺伝子についてトランスジェニックマウスが作成されたが,いずれも生物機能モデル又はヒト疾患モデルとなる可能性があるため病理学的,生化学的検討を行なっている。P450,インシュリン,APOEなどの遺伝子導入マウスが現在有望なモデルになりつゝある。以上の他,ジ-ンタ-ゲッティング法の導入と確立にとり組んだ。その結果,東海大,熊大,名大においてそれぞれ相同組換え体胚幹細胞が得られ,注入法によるキメラマウス作成に成功した。今後これらの子孫から計画突然変異マウスが得られるものと期待できる。特に劣性遺伝病モデルマウスの作成には,アンチセンス法とともに,ジ-ンタ-ゲッティング法が重要となる。

Research Products

(39 results)

All Other

All Publications (39 results)

[Publications] M.Katsuki et al.: "Diversity,development,ligands,and probable functions of γδ T cells." Cold Spring Harbor Symp.Quant.Biol.54. 31-44 (1990)
[Publications] M.Katsuki et al.: "Transgenic mice demonstrate that epithelial homing of γδ T cells is determined by cell lineages independent of T cell." J.Exp.Med.171. 1015-1026 (1990)
[Publications] M.Katsuki et al.: "Developmental potential of haploidーderived parthenogenic cells in mouse chimeric embryos." Dev.Growth Differ.32. 139-144 (1990)
[Publications] M.KatsuKi et al.: "The human renin gene in transgenic mice." J.Cardiovasc.Pharmacol.16. S8-S10 (1990)
[Publications] Y.Iwakura et al.: "Induction of interferonーα by interferonーβ,but not of interferonーβ by interferonーα,in the mouse." Virol.176. 30-38 (1990)
[Publications] T.Hirano & Y.Iwakura: "A novel transcriptional regulatory factor that binds to the polyoma virus enhancer in a developmental stagespecific manner." Biochimie.72. 327-336 (1990)
[Publications] H.Ohkubo et al.: "Immunohistochemical study of a rat membrane protein which induces a selective potassium permeation." J.Memb.Biol.113. 39-47 (1990)
[Publications] H.Ohkubo et al.: "Elevated angiotensinogen mRNA levels in rat liver by nephrectomy." Am.J.Physiol.258. E413-E417 (1990)
[Publications] H.Ohkubo,M.Katsuki et al.: "Generation of transgenic mice with elevated blood pressure by introduction of the rat renin and angiotensinogen genes." Proc.Natl.Acad.Sci.USA. 87. 5153-5157 (1990)
[Publications] H.Ohkubo et al.: "Characterization of gene organization and generation of heterogeneous mRNA species of rat I_<sk> protein." J.Biochem.108. 200-206 (1990)
[Publications] H.OHkubo et al.: "Cloning of a fullーlength cDNA encoding bovine thymus poly(ADPーribose) synthetase." Gene. 90. 249-254 (1990)
[Publications] H.Ohkubo et al.: "Clonig and expression of a cDNA encoding an endothelin receptor." Nature. 348. 730-732 (1990)
[Publications] Y.Ohshima et al.: "ーglobin transcripts carrying a single intron with three adjacent nucleotides of 5'exon are efficiently spliced <in vitro>___ー irrespective of intron position・・・・・・" Nucleic Acid Res.18. 4671-4676 (1990)
[Publications] Y.Ohshima et al.: "Surveying <cis>___ーーacting sequences of preーmRNA by adding antisense 2'ーOーmethyl oligoribonucleotides to a splicing reaction." J.Biochem.108. 399-405 (1990)
[Publications] Y.Ohshima et al.: "The letー23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily." Nature. 348. 693-699 (1990)
[Publications] T.Kamataki et al.: "Fetusーspecific expression of a from of cytochrome P450 in human livers." Biochemistry. 29. 4430-4433 (1990)
[Publications] T.Kamataki et al.: "Metabolic activation of aflatoxin B_1 and 2ーaminoー3ーmethyl imidazo(4,5ーf)ーquinoline by human adult and fetal livers." Cancer Res.50. 2641-2645 (1990)
[Publications] T.Kamataki et al.: "Isolation od cDNAs coding for three different forms of liver microsomal cytochrome Pー450 from polychrolinated biphenylーtreated beagle dogs." Mol.Pharmacol.38. 644-651 (1990)
[Publications] M.Kimura,M.Katsuki et al.: "Most tumors in transgenic mice with human cーHaー<ras>___ー gene contained somatically activated transgenes." Oncogene. 5. 1195-1200 (1990)
[Publications] H.Kondoh et al.: "Rapid and transient decrease of Nーmyc expression in retinoic acidーinduced differentiation of OTF9 tratocarcinoma stem cells." Mol.Cell.Biol.10. 486-491 (1990)
[Publications] H.Kondoh et al.: "Functional cooperation of lensーspecific and nonーspecific elements in the 1ーcrystallin enhancer." Mol.Cell.Biol.10. 958-964 (1990)
[Publications] H.Kondoh et al.: "Organization and expression of the chicken Nーmyc gene." Mol.Cell.Biol.10. 2017-2026 (1990)
[Publications] H.Kondoh: "The mechanism of ーcrystallin gene regulation: cooperation of lensーspecific and nonーspecific elements." Dev.Growth Differ.32. 125-130 (1990)
[Publications] Wakamatsu & H.Kondoh et al.: "Conditions for detection of embryonic Nーmyc expression by <in situ>___ー hybridization." Acta Histochem.Cytochem.23. 367-374 (1990)
[Publications] H.Kondoh et al.: "A mouse embryonic stem cell line showing pluripotency of differentiation in early embryos and ubiquitous βーgalactosidase expression" Cell Differ.Develop.29. 181-186 (1990)
[Publications] H.Kondoh et al.: "A retinoic acid responsive gene,MK,produces a secreted protein with heparin binding activity" Biochem.Biophys.Res.Commun.171. 603-609 (1990)
[Publications] H.Kondoh et al.: "Tissueーdistribution of Nーmyc expression in the early organogenesis period of the mouse embryo" Dev.Growth Differ.33. 29-36 (1991)
[Publications] H.Kondoh et al.: "Expression of the chickin‘δ2ーcrystallin'gene in mouse cells:evidence for encoding of argininosuccinate lyase" Gene. (1991)
[Publications] T.Shiba et al.: "Production of enkephalin in tobacco protoplasts using tabacco mosaic virus RNA vector" FEBS Lett.1269. 73-76 (1990)
[Publications] T.Shiba et al.: "Constitutive and inducible expression of a transgene directed by heterologous promoters in a trout liver cell line" Biochem.Biophys.Res Commun.(1991)
[Publications] Y.Nishida et al.: "Drosophila proliferating cell nuclear antigen (cyclin) gene:Structure,expression during development,and specific binding of homeodomain proteins to its 5'ーflanking region" Mol.Cell.Biol.10. 872-879 (1990)
[Publications] Y.Nishida et al.: "Clonig and nucleotide sequence of cDNA for Ki antigen,a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosu" Clin.Exp.Immunol.79. 209-214 (1990)
[Publications] M.Mori et al.: "Promoter and 11ーkilobase upsteam enhancer elements responsible for hepatoma cellーspecific expression of the rat ornithine transcarbamylase gene" Mol.Cell.Biol.10. 1180-1191 (1990)
[Publications] M.Mori et al.: "Molecular basis of argininemia:Identification of two discrete frameーshift deletions in the liverーtype arginase gene" J.Clin.Invest.86. 347-350 (1990)
[Publications] M.Mori,K.Yamamura et al.: "Correction of ornithine transcarbamylase (OTC) deficiency in spfーash mice by introduction of rat OTC gene" FEBS Lett.(1991)
[Publications] K.Yamamura et al.: "Establishment of a pancreatic β cell line that retains glucoseーinducible insulin secretion:special reference to expression of glucose transporter isoforms" Endocrinol.127. 126-132 (1990)
[Publications] K.Yamamura et al.: "Direct evidence for the contribution of the unique 1ーA^<NOD> to the development of insulitis in nonーobese diabetic mice" Nature. 345. 722-724 (1990)
[Publications] K.Yamamura et al.: "Tissueーspecific expression of rat pyruvate kinase L/chloramphenicol acetyltransferase fusion gene in transgenic mice and its regulation by diet and insulin" Biochem.Biophys.Res.Commun.171. 243-249 (1990)
[Publications] K.Yamamura et al.: "Correlation of tissueーspecific methylation with gene inactivity in hepatitis B virus transgenic mice" Jpn.J.Cancer Res.81. 1265-1271 (1990)

1990 Fiscal Year Annual Research Report

外来遺伝子DNA導入による新しいモデル動物の開発

Principal Investigator

勝木 元也 東海大学, 医学部, 教授 (20051732)

Research Products

[Publications] M.Katsuki et al.: "Diversity,development,ligands,and probable functions of γδ T cells." Cold Spring Harbor Symp.Quant.Biol.54. 31-44 (1990)

[Publications] M.Katsuki et al.: "Transgenic mice demonstrate that epithelial homing of γδ T cells is determined by cell lineages independent of T cell." J.Exp.Med.171. 1015-1026 (1990)

[Publications] M.Katsuki et al.: "Developmental potential of haploidーderived parthenogenic cells in mouse chimeric embryos." Dev.Growth Differ.32. 139-144 (1990)

[Publications] M.KatsuKi et al.: "The human renin gene in transgenic mice." J.Cardiovasc.Pharmacol.16. S8-S10 (1990)

[Publications] Y.Iwakura et al.: "Induction of interferonーα by interferonーβ,but not of interferonーβ by interferonーα,in the mouse." Virol.176. 30-38 (1990)

[Publications] T.Hirano & Y.Iwakura: "A novel transcriptional regulatory factor that binds to the polyoma virus enhancer in a developmental stagespecific manner." Biochimie.72. 327-336 (1990)

[Publications] H.Ohkubo et al.: "Immunohistochemical study of a rat membrane protein which induces a selective potassium permeation." J.Memb.Biol.113. 39-47 (1990)

[Publications] H.Ohkubo et al.: "Elevated angiotensinogen mRNA levels in rat liver by nephrectomy." Am.J.Physiol.258. E413-E417 (1990)

[Publications] H.Ohkubo,M.Katsuki et al.: "Generation of transgenic mice with elevated blood pressure by introduction of the rat renin and angiotensinogen genes." Proc.Natl.Acad.Sci.USA. 87. 5153-5157 (1990)

[Publications] H.Ohkubo et al.: "Characterization of gene organization and generation of heterogeneous mRNA species of rat I_<sk> protein." J.Biochem.108. 200-206 (1990)

[Publications] H.OHkubo et al.: "Cloning of a fullーlength cDNA encoding bovine thymus poly(ADPーribose) synthetase." Gene. 90. 249-254 (1990)

[Publications] H.Ohkubo et al.: "Clonig and expression of a cDNA encoding an endothelin receptor." Nature. 348. 730-732 (1990)

[Publications] Y.Ohshima et al.: "ーglobin transcripts carrying a single intron with three adjacent nucleotides of 5'exon are efficiently spliced <in vitro>___ー irrespective of intron position・・・・・・" Nucleic Acid Res.18. 4671-4676 (1990)

[Publications] Y.Ohshima et al.: "Surveying <cis>___ーーacting sequences of preーmRNA by adding antisense 2'ーOーmethyl oligoribonucleotides to a splicing reaction." J.Biochem.108. 399-405 (1990)

[Publications] Y.Ohshima et al.: "The letー23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily." Nature. 348. 693-699 (1990)

[Publications] T.Kamataki et al.: "Fetusーspecific expression of a from of cytochrome P450 in human livers." Biochemistry. 29. 4430-4433 (1990)

[Publications] T.Kamataki et al.: "Metabolic activation of aflatoxin B_1 and 2ーaminoー3ーmethyl imidazo(4,5ーf)ーquinoline by human adult and fetal livers." Cancer Res.50. 2641-2645 (1990)

[Publications] T.Kamataki et al.: "Isolation od cDNAs coding for three different forms of liver microsomal cytochrome Pー450 from polychrolinated biphenylーtreated beagle dogs." Mol.Pharmacol.38. 644-651 (1990)

[Publications] M.Kimura,M.Katsuki et al.: "Most tumors in transgenic mice with human cーHaー<ras>___ー gene contained somatically activated transgenes." Oncogene. 5. 1195-1200 (1990)

[Publications] H.Kondoh et al.: "Rapid and transient decrease of Nーmyc expression in retinoic acidーinduced differentiation of OTF9 tratocarcinoma stem cells." Mol.Cell.Biol.10. 486-491 (1990)

[Publications] H.Kondoh et al.: "Functional cooperation of lensーspecific and nonーspecific elements in the 1ーcrystallin enhancer." Mol.Cell.Biol.10. 958-964 (1990)

[Publications] H.Kondoh et al.: "Organization and expression of the chicken Nーmyc gene." Mol.Cell.Biol.10. 2017-2026 (1990)

[Publications] H.Kondoh: "The mechanism of ーcrystallin gene regulation: cooperation of lensーspecific and nonーspecific elements." Dev.Growth Differ.32. 125-130 (1990)

[Publications] Wakamatsu & H.Kondoh et al.: "Conditions for detection of embryonic Nーmyc expression by <in situ>___ー hybridization." Acta Histochem.Cytochem.23. 367-374 (1990)

[Publications] H.Kondoh et al.: "A mouse embryonic stem cell line showing pluripotency of differentiation in early embryos and ubiquitous βーgalactosidase expression" Cell Differ.Develop.29. 181-186 (1990)

[Publications] H.Kondoh et al.: "A retinoic acid responsive gene,MK,produces a secreted protein with heparin binding activity" Biochem.Biophys.Res.Commun.171. 603-609 (1990)

[Publications] H.Kondoh et al.: "Tissueーdistribution of Nーmyc expression in the early organogenesis period of the mouse embryo" Dev.Growth Differ.33. 29-36 (1991)

[Publications] H.Kondoh et al.: "Expression of the chickin‘δ2ーcrystallin'gene in mouse cells:evidence for encoding of argininosuccinate lyase" Gene. (1991)

[Publications] T.Shiba et al.: "Production of enkephalin in tobacco protoplasts using tabacco mosaic virus RNA vector" FEBS Lett.1269. 73-76 (1990)

[Publications] T.Shiba et al.: "Constitutive and inducible expression of a transgene directed by heterologous promoters in a trout liver cell line" Biochem.Biophys.Res Commun.(1991)

[Publications] Y.Nishida et al.: "Drosophila proliferating cell nuclear antigen (cyclin) gene:Structure,expression during development,and specific binding of homeodomain proteins to its 5'ーflanking region" Mol.Cell.Biol.10. 872-879 (1990)

[Publications] Y.Nishida et al.: "Clonig and nucleotide sequence of cDNA for Ki antigen,a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosu" Clin.Exp.Immunol.79. 209-214 (1990)

[Publications] M.Mori et al.: "Promoter and 11ーkilobase upsteam enhancer elements responsible for hepatoma cellーspecific expression of the rat ornithine transcarbamylase gene" Mol.Cell.Biol.10. 1180-1191 (1990)

[Publications] M.Mori et al.: "Molecular basis of argininemia:Identification of two discrete frameーshift deletions in the liverーtype arginase gene" J.Clin.Invest.86. 347-350 (1990)

[Publications] M.Mori,K.Yamamura et al.: "Correction of ornithine transcarbamylase (OTC) deficiency in spfーash mice by introduction of rat OTC gene" FEBS Lett.(1991)

[Publications] K.Yamamura et al.: "Establishment of a pancreatic β cell line that retains glucoseーinducible insulin secretion:special reference to expression of glucose transporter isoforms" Endocrinol.127. 126-132 (1990)

[Publications] K.Yamamura et al.: "Direct evidence for the contribution of the unique 1ーA^<NOD> to the development of insulitis in nonーobese diabetic mice" Nature. 345. 722-724 (1990)

[Publications] K.Yamamura et al.: "Tissueーspecific expression of rat pyruvate kinase L/chloramphenicol acetyltransferase fusion gene in transgenic mice and its regulation by diet and insulin" Biochem.Biophys.Res.Commun.171. 243-249 (1990)

[Publications] K.Yamamura et al.: "Correlation of tissueーspecific methylation with gene inactivity in hepatitis B virus transgenic mice" Jpn.J.Cancer Res.81. 1265-1271 (1990)

勝木元也東海大学, 医学部, 教授 (20051732)