1989 Fiscal Year Annual Research Report

野性遺伝子および外来遺伝子のDNA導入マウスの系統化システムの開発とその基礎的研究

Research Project

Project/Area Number	01619005
Research Institution	Central Institute for Experimental Animals
Principal Investigator	野村達次実験動物中央研究所, 所長 (10072399)
Co-Investigator(Kenkyū-buntansha)	早川純一郎金沢大学, 医学部・附属動物実験施設, 助教授 (50110622) 光岡知足東京大学, 農学部・実験動物学教室, 教授 (30157549) 豊田裕東京大学, 医科学研究所・獣医学研究部, 教授 (90050418) 横山峯介実験動物中央研究所, 生殖研究室, 室長 (40090930)
Keywords	生物機能モデル / ヒト疾患モデル / 遺伝モニタリング / 微生物モニタリング / トランスジェニックマウス / 遺伝子導入動物 / 系統保存 / 発生工学技術
Research Abstract	1.研究の目的現代のバイオサイエンスの知識と技術を用いて作成された遺伝子導入動物は、生物機能モデルやヒト疾患モデルとして研究に重要な役割を果たすに至った。本研究は、このように新しく開発された遺伝子導入動物を、実験動物として使い得るようにするため、系統の維持保存システムを確立し、品質管理と実験条件の一定化のため遺伝的モニタリングおよび微生物モニタリングのシステムを確立することを目的とする。 2.研究の成果数多く作成されたトランスジェニックマウスにおける導入遺伝子の染色体上の組み込まれた部位をinsitu法によって調べる方法を確立した。その結果、ヒトIL2遺伝子導入マウス4系統はすべて異なる染色体上に導入遺伝子を組み込んでいることが明らかにされた。これらのマウスはすべて運動失調を示すことから、ヒトIL2遺伝子は機能的に働き、新しい自己免疫疾患モデルの可能性を示した。さらに、体外受精、卵巣移植等の発生工学技術を用いて生殖行動をとれないトランスジェニックマウスから、子孫を得ることに成功し、受精卵や胚の凍結によって任意の時期に大量の子孫を得る方法も確立した。これらの技術の完成は、従来の動物実験の方法を一変したものである。次に、自然界には存在しないヒト遺伝子を導入されたマウスにおける導入遺伝子の経世代的安定性を調べた結果、ほとんどの系統でメンデルの法則に従って安定に伝達されることが明らかとなった。いくつかの例外については現在その原因を検討中である。以上の結果、新しい遺伝子導入動物の系統の維持保存方法が確立し、導入遺伝子を指標としたモニタリングシステムも確立した。今後は、これらの方法を動物実験に応用し、問題を探っていきたい。

Research Products

(44 results)

All Other

All Publications (44 results)

[Publications] Fukamizu A.,Yokoyama M.,Nomura T.,et al.: "Tissueーspecific expression of the human renin gene in transgenic mice" Biochem.Biophy.Res.Commun.165. 826-832 (1989)
[Publications] Yamaguchi R.,Iwai H.,et al.: "Antigenic variation among Sendai virus strains detected by monoclonal antibodies" Microbiol.Immunol.33. 133-139 (1989)
[Publications] Machii K.,Iwai H.,et al.: "Infection of rabbits with Sendai virus" Lab.Anim.Sci.39. 334-337 (1989)
[Publications] Itoh T.,Iwai H.,et al.: "Comparison of lung virus titers in susceptible and resistant inbred mouse strains against Sendai virus infection." Exp.Anim.38. 269-273 (1989)
[Publications] Iwai H.,et al.: "Cooperation between humoral factor(s)and Lytー2+ T cells in effective clearance of Sendai virus from infected mouse lungs" Microbiol.Immunol.33. 915-927 (1989)
[Publications] Yamamoto S.,Iwai H.,et al.: "Adoptive immunity to Mycobacterium bovis strain bacillus CalmetteーGuerin by longーterm cultured Tーcell line in nude mice" Immunology. 68. 253-259 (1989)
[Publications] Saegusa J.,Iwai H.,et al.: "Antinucleolar autoantibody induced in mice by mercuric chloride" Industrial Health.
[Publications] Kasai M.,et al.: "A simple method for mouse embryo cryopreservation in a low toxicity vitrification solution,without appreciable loss of viability" J.Reprod.Fert.
[Publications] Katoh H.,et al.: "Mapping of the Esー4 locus and linear order of esterase genes(Linkage Group V:LGV)in the rat" Biochem.Genet.27. 641-646 (1989)
[Publications] Katoh H.,et al.: "Research News:Hotfoot(ho Jic),semidominant short tail(T Jic),and deficiency of serum lgGL subclass" Mouse News Letter. 84. 94-95 (1989)
[Publications] Hosono M.,Katoh H.,et al.: "New recombinant inbred strains" Mouse News Letter. 85. 8-9 (1989)
[Publications] Wada H.,Taya C.,et al.: "Cell typeーspecific expression of the genes for the protein kinase C family:Down regulation of mRNAs for PKCα and nPKCε upon in vitro differentiation of a mouse neuroblastoma cell line neuro 2a" Biochem.Biophys.Res.Commun.165. 533-538 (1989)
[Publications] Kohno K.,Toyoda Y.,et al.: "Loss of fertilizability of cumulusfree mouse oocytes upon exposure to DMSO and its prevention by fetal calf serum" J.Mammal.Ova.Res.6. 156-161 (1989)
[Publications] Hamano S.,Toyoda Y.,et al.: "In vitro capacitation of boar ejaculated spermatozoa:effect of conditioned media prepared from preincubated sperm suspension" Gamete Res.24. 483-489 (1989)
[Publications] Nakagawa N.: "High survival rate of unfertilized mouse oocytes after vitrification" J.Reprod.Fert.87. 479-483 (1989)
[Publications] Ogura A.,Nakagawa M.,et al.: "Development of nephrotic ICGN miceーthe origin,reproductive ability,and incidence of glomerulonephritis" Exp.Anim.38. 349-352 (1989)
[Publications] Ogura A.,Nakagawa M.,et al.: "Characteristics of mutant mice(ICGN)with spontaneous renal lesions:a new model for human nephrotic syndrome" Lab.Anim.23. 169-174 (1989)
[Publications] Hayashi M.,Namioka S.,et al.: "The effects of ionizing radiation on promoterーdependent RNA systhesis" Jpn.J,Vet.Res.37. 15-19 (1989)
[Publications] Deguchi E.,Namioka S.: "Synthesis ability of amino acids and protein from nonprotein nitrogen and role of intestinal flora on this utilization in pigs" Bifidobacteria Microflora. 8. 1-12 (1989)
[Publications] Isogai E.,Namioka S.,et al.: "Oral flora of mongrel and Beagle dogs with periodontal disease" Jpn.J.Vet.Sci.51. 110-118 (1989)
[Publications] Isogai E.,Namioka S.,et al.: "Escherichia coli associated endotoxemia in dogs with parvovirus infection" Jpn.J.Vet.Sci.51. 597-606 (1989)
[Publications] Yamashita T.,Namioka S.,et al.: "Improved embryo adhesion method for rat chimera production" Lab.Anim.Sci.39. 446-448 (1989)
[Publications] Isogai H.,Namioka S.,et al.: "Biological effects of lipopolysaccharide from Achromobacter stenohalis on lymphocytes and macrophages" Jpn.J.Vet.Sci.51. 1003-1010 (1989)
[Publications] Isogai H.,Namioka S.,et al.: "Effectes of lipopolysaccharide from Bacteroides gingivalis in sus rats" Jpn.J.Vet.Sci.51. 1095-1097 (1989)
[Publications] Nishimura M.,et al.: "Being rat:A new animal model of ChekiakーHigashi Syndrom" Blood. 74. 270-273 (1989)
[Publications] Nose M.,Nishimura M.,et al.: "Analysis of granulomatous arteritis in MRL/Mp autoimmune disease mice bearing lymphoproliferative genes" Am.J.Pathol.135. 271-280 (1989)
[Publications] Fujishima Y.,Nishimura M.,et al.: "Restriction of fragment length polymorphism analysis of major histocompatibility complex genes in the nonーobese diabetic mouse strain and its nonーdiabetic sister strains" Diabetologia. 32. 118-125 (1989)
[Publications] Watanabe T.,Nishimura M.,et al.: "Evolutionary relationships between laboratory mice and subspecies of Mus musculus based on the restriction fragment length variants of the chymotrypsin gene at the Prtー2 locus" Biochem.Genet.27. 119-130 (1989)
[Publications] Mori Y.,Nishimura M.,et al.: "Effect of CAMOSTAT on pancreatic impairment in WBN/Kob rats" Biomed.Res.10. 157-166 (1989)
[Publications] Imamura Y.,Hayakawa J.,et al.: "Urea cycle disorder in C3HーHー2° mice with juvenile steatosis of viscera" FEBS Lett.260. 119-121 (1990)
[Publications] Koizumi T.,Hayakawa J.,et al.: "Blood ammonia concentration in mice:Normal reference values and changes during growth" Lab.Anim.Sci.40.
[Publications] Itoh K.,Mitsuoka T.,et al.: "Gastrointestinal flora of cotton rats" Lab.Anim.23. 62-65 (1989)
[Publications] Kawamura S.,Mitsuoka T.,et al.: "Initial phase of infection with Tyzzer′s organism in cultured mouse hepatocytes" J.Gen.Microbiol.135. 2099-2106 (1989)
[Publications] Kondo Y.,Yamada J.,et al.: "Genetic polymorphism of tear proteins in the rat" Biochem.Genet.26. 683-691 (1988)
[Publications] Mori M.,Yamada J.,et al.: "Restriction fragment length polymorphisms of angiotensinogen gene in inbred rat strains and mapping of the gene on chromosome 19q" Cytogene.Cell Genet.50. 42-45 (1989)
[Publications] Yamada T.,Yamada J.,et al.: "Assignment of tremulous body mutant gene Zitter(zi)to linkage group IV of the rat(Rattus norvegicus)" J.Herid.80. 383-386 (1989)
[Publications] Katsuki M.,Yokoyama M.,et al.: "Lymphocyte infiltration into cerebellum in transgenic mice carrying human ILー2 gene" Int.Immunol.1. 214-218 (1989)
[Publications] Koudo Y.,Yamada J.,et al.: "Second genetic polymorphism of tear proteins in the rat(Rtpー2)" Exp.Anim.38. 327-331 (1989)
[Publications] Kimura M.,Yokoyama M.,et al.: "Restoration of myelin formation by a single type of myelin basic protein in transgenic shiverer mice" Proc.Natl.Acad.Sci.USA. 86. 5661-5665 (1989)
[Publications] Niwa M.,Wakasugi N.: "Abnormal development of preimplamtation embryos derived from intersubspecific hybrids between Mus musculus molossinus and M.m.domesticus" Zool.Sci.(1990)
[Publications] Tsuzuki M.,Wakasugi N.,: "Throatーtuft:a newly discovered morphological mutation in Japanese quail" J.Hered.(1990)
[Publications] Tsuzuki M.,Wakasugi N.,et al.: "An allelism test for plumage color mutant genes,D(black)and ps(pansy),in Japanese Quail(Coturnix conturnix japonica)" Jpn.Poult.Sci.(1990)
[Publications] Matsuyama M.,Katoh H.,et al.: "Immuneーdeficient animals in experimental medicine(6th Int.Workshop on ImmuneーDeficient Animals)" Basel Karger, PP27-31 (1989)
[Publications] Toyoda Y.,et al.: "Development of preimplantation embyos and their environment" Alan R.Liss, PP171-179 (1989)

1989 Fiscal Year Annual Research Report

野性遺伝子および外来遺伝子のDNA導入マウスの系統化システムの開発とその基礎的研究

Principal Investigator

野村 達次 実験動物中央研究所, 所長 (10072399)

Research Products

[Publications] Fukamizu A.,Yokoyama M.,Nomura T.,et al.: "Tissueーspecific expression of the human renin gene in transgenic mice" Biochem.Biophy.Res.Commun.165. 826-832 (1989)

[Publications] Yamaguchi R.,Iwai H.,et al.: "Antigenic variation among Sendai virus strains detected by monoclonal antibodies" Microbiol.Immunol.33. 133-139 (1989)

[Publications] Machii K.,Iwai H.,et al.: "Infection of rabbits with Sendai virus" Lab.Anim.Sci.39. 334-337 (1989)

[Publications] Itoh T.,Iwai H.,et al.: "Comparison of lung virus titers in susceptible and resistant inbred mouse strains against Sendai virus infection." Exp.Anim.38. 269-273 (1989)

[Publications] Iwai H.,et al.: "Cooperation between humoral factor(s)and Lytー2+ T cells in effective clearance of Sendai virus from infected mouse lungs" Microbiol.Immunol.33. 915-927 (1989)

[Publications] Yamamoto S.,Iwai H.,et al.: "Adoptive immunity to Mycobacterium bovis strain bacillus CalmetteーGuerin by longーterm cultured Tーcell line in nude mice" Immunology. 68. 253-259 (1989)

[Publications] Saegusa J.,Iwai H.,et al.: "Antinucleolar autoantibody induced in mice by mercuric chloride" Industrial Health.

[Publications] Kasai M.,et al.: "A simple method for mouse embryo cryopreservation in a low toxicity vitrification solution,without appreciable loss of viability" J.Reprod.Fert.

[Publications] Katoh H.,et al.: "Mapping of the Esー4 locus and linear order of esterase genes(Linkage Group V:LGV)in the rat" Biochem.Genet.27. 641-646 (1989)

[Publications] Katoh H.,et al.: "Research News:Hotfoot(ho Jic),semidominant short tail(T Jic),and deficiency of serum lgGL subclass" Mouse News Letter. 84. 94-95 (1989)

[Publications] Hosono M.,Katoh H.,et al.: "New recombinant inbred strains" Mouse News Letter. 85. 8-9 (1989)

[Publications] Wada H.,Taya C.,et al.: "Cell typeーspecific expression of the genes for the protein kinase C family:Down regulation of mRNAs for PKCα and nPKCε upon in vitro differentiation of a mouse neuroblastoma cell line neuro 2a" Biochem.Biophys.Res.Commun.165. 533-538 (1989)

[Publications] Kohno K.,Toyoda Y.,et al.: "Loss of fertilizability of cumulusfree mouse oocytes upon exposure to DMSO and its prevention by fetal calf serum" J.Mammal.Ova.Res.6. 156-161 (1989)

[Publications] Hamano S.,Toyoda Y.,et al.: "In vitro capacitation of boar ejaculated spermatozoa:effect of conditioned media prepared from preincubated sperm suspension" Gamete Res.24. 483-489 (1989)

[Publications] Nakagawa N.: "High survival rate of unfertilized mouse oocytes after vitrification" J.Reprod.Fert.87. 479-483 (1989)

[Publications] Ogura A.,Nakagawa M.,et al.: "Development of nephrotic ICGN miceーthe origin,reproductive ability,and incidence of glomerulonephritis" Exp.Anim.38. 349-352 (1989)

[Publications] Ogura A.,Nakagawa M.,et al.: "Characteristics of mutant mice(ICGN)with spontaneous renal lesions:a new model for human nephrotic syndrome" Lab.Anim.23. 169-174 (1989)

[Publications] Hayashi M.,Namioka S.,et al.: "The effects of ionizing radiation on promoterーdependent RNA systhesis" Jpn.J,Vet.Res.37. 15-19 (1989)

[Publications] Deguchi E.,Namioka S.: "Synthesis ability of amino acids and protein from nonprotein nitrogen and role of intestinal flora on this utilization in pigs" Bifidobacteria Microflora. 8. 1-12 (1989)

[Publications] Isogai E.,Namioka S.,et al.: "Oral flora of mongrel and Beagle dogs with periodontal disease" Jpn.J.Vet.Sci.51. 110-118 (1989)

[Publications] Isogai E.,Namioka S.,et al.: "Escherichia coli associated endotoxemia in dogs with parvovirus infection" Jpn.J.Vet.Sci.51. 597-606 (1989)

[Publications] Yamashita T.,Namioka S.,et al.: "Improved embryo adhesion method for rat chimera production" Lab.Anim.Sci.39. 446-448 (1989)

[Publications] Isogai H.,Namioka S.,et al.: "Biological effects of lipopolysaccharide from Achromobacter stenohalis on lymphocytes and macrophages" Jpn.J.Vet.Sci.51. 1003-1010 (1989)

[Publications] Isogai H.,Namioka S.,et al.: "Effectes of lipopolysaccharide from Bacteroides gingivalis in sus rats" Jpn.J.Vet.Sci.51. 1095-1097 (1989)

[Publications] Nishimura M.,et al.: "Being rat:A new animal model of ChekiakーHigashi Syndrom" Blood. 74. 270-273 (1989)

[Publications] Nose M.,Nishimura M.,et al.: "Analysis of granulomatous arteritis in MRL/Mp autoimmune disease mice bearing lymphoproliferative genes" Am.J.Pathol.135. 271-280 (1989)

[Publications] Fujishima Y.,Nishimura M.,et al.: "Restriction of fragment length polymorphism analysis of major histocompatibility complex genes in the nonーobese diabetic mouse strain and its nonーdiabetic sister strains" Diabetologia. 32. 118-125 (1989)

[Publications] Watanabe T.,Nishimura M.,et al.: "Evolutionary relationships between laboratory mice and subspecies of Mus musculus based on the restriction fragment length variants of the chymotrypsin gene at the Prtー2 locus" Biochem.Genet.27. 119-130 (1989)

[Publications] Mori Y.,Nishimura M.,et al.: "Effect of CAMOSTAT on pancreatic impairment in WBN/Kob rats" Biomed.Res.10. 157-166 (1989)

[Publications] Imamura Y.,Hayakawa J.,et al.: "Urea cycle disorder in C3HーHー2° mice with juvenile steatosis of viscera" FEBS Lett.260. 119-121 (1990)

[Publications] Koizumi T.,Hayakawa J.,et al.: "Blood ammonia concentration in mice:Normal reference values and changes during growth" Lab.Anim.Sci.40.

[Publications] Itoh K.,Mitsuoka T.,et al.: "Gastrointestinal flora of cotton rats" Lab.Anim.23. 62-65 (1989)

[Publications] Kawamura S.,Mitsuoka T.,et al.: "Initial phase of infection with Tyzzer′s organism in cultured mouse hepatocytes" J.Gen.Microbiol.135. 2099-2106 (1989)

[Publications] Kondo Y.,Yamada J.,et al.: "Genetic polymorphism of tear proteins in the rat" Biochem.Genet.26. 683-691 (1988)

[Publications] Mori M.,Yamada J.,et al.: "Restriction fragment length polymorphisms of angiotensinogen gene in inbred rat strains and mapping of the gene on chromosome 19q" Cytogene.Cell Genet.50. 42-45 (1989)

[Publications] Yamada T.,Yamada J.,et al.: "Assignment of tremulous body mutant gene Zitter(zi)to linkage group IV of the rat(Rattus norvegicus)" J.Herid.80. 383-386 (1989)

[Publications] Katsuki M.,Yokoyama M.,et al.: "Lymphocyte infiltration into cerebellum in transgenic mice carrying human ILー2 gene" Int.Immunol.1. 214-218 (1989)

[Publications] Koudo Y.,Yamada J.,et al.: "Second genetic polymorphism of tear proteins in the rat(Rtpー2)" Exp.Anim.38. 327-331 (1989)

[Publications] Kimura M.,Yokoyama M.,et al.: "Restoration of myelin formation by a single type of myelin basic protein in transgenic shiverer mice" Proc.Natl.Acad.Sci.USA. 86. 5661-5665 (1989)

[Publications] Niwa M.,Wakasugi N.: "Abnormal development of preimplamtation embryos derived from intersubspecific hybrids between Mus musculus molossinus and M.m.domesticus" Zool.Sci.(1990)

[Publications] Tsuzuki M.,Wakasugi N.,: "Throatーtuft:a newly discovered morphological mutation in Japanese quail" J.Hered.(1990)

[Publications] Tsuzuki M.,Wakasugi N.,et al.: "An allelism test for plumage color mutant genes,D(black)and ps(pansy),in Japanese Quail(Coturnix conturnix japonica)" Jpn.Poult.Sci.(1990)

[Publications] Matsuyama M.,Katoh H.,et al.: "Immuneーdeficient animals in experimental medicine(6th Int.Workshop on ImmuneーDeficient Animals)" Basel Karger, PP27-31 (1989)

[Publications] Toyoda Y.,et al.: "Development of preimplantation embyos and their environment" Alan R.Liss, PP171-179 (1989)

野村達次実験動物中央研究所, 所長 (10072399)