1992 Fiscal Year Annual Research Report

野生遺伝子および外来遺伝子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	04206104
Research Institution	Central Institute for Experimental Animals
Principal Investigator	野村達次 (財)実験動物中央研究所, 所長 (10072399)
Co-Investigator(Kenkyū-buntansha)	林崎良英理化学研究所, ライフサイエンス筑波研究センター, 研究員 (70192705) 早川純一郎金沢大学, 医学部, 教授 (50110622) 中潟直己日本生物科学研究所, 第5研究部, 研究員 (30159058) 田中亀代次大阪大学, 細胞生体工学センター, 教授 (80144450) 小池智東京都臨床医学総合研究所, 微生物研究部門, 研究員 (30195630)
Keywords	発生工学 / ヒト疾患モデル / 生物機能モデル / 色素性乾皮症 / ポリオウイルス受容体 / 凍結保存 / 体外受精
Research Abstract	本研究は現代の発生工学技術を駆使して作成されたヒト疾患モデルや生物機能モデルマウスを系統化し,維持保存するとともに,新しい効率的な動物実験系の確立を目的とする。この目的に従って本年度は次のような研究成果が得られた。 1)マウス胚,未受精卵子,精子の凍結保存法の確立。種々の耐凍剤や凍結方法の検討によって,未受精卵子および精子をそれぞれ凍結した後融解し,体外受精を行い産仔を得ることに成功した。このことによって,すでに確立していた2細胞期胚や8細胞期胚の凍結保存法と併せていつでも任意の組合せの遺伝的背景をもつマウスを個体からではなく試験管内から計画的に生産する道が開かれたといえる。 2)ヒト疾患モデルマウスとして,色素性乾皮症で認められる欠損遺伝子の一つであるXPAC遺伝子欠損マウスを作ることに成功した。このマウスはアルキル化剤に対して極めて感受性が高く,細胞の性質はヒトの遺伝病のものと酷似していたが,神経症状等では異なるものであった。今後さらに検討し,紫外線や他の化学物質による疾病についても検討する価値があるものと結論された。 3)ポリオウイルス受容体遺伝子導入マウス(PVRマウス)はヒトのポリオウイルスが感染し,麻痺等の症状を呈することが示された。このマウスはカニクイザルに代るポリオワクチンの検定系になることが期待されるものとなった。 4)実験用マウスをウイルス抵抗性にする試みは,今のところ成功していない。また,導入遺伝子の挿入部位の解析を行う技術が確立した。以上の成果は,単にそれぞれの成果として独立に評価されるのみならず,体外受精,凍結保存の組み合わせによって,大量の実験動物を計画的に用いる動物実験系が確立した点でも評価できるものと考えられる。

Research Products
(30 results)

All Other

All Publications (30 results)

[Publications] Kobayashi,K: "Genetic alteration of catecholamine specificity in transgenic mice" Proc Natl Acad Sci USA. 89. 1631-1635 (1992)
[Publications] Ito,M: "Preservation of an inbred mouse strain by the storage of frozen embryos:An estimate of the time of occurrence of a serum lgG1 deficiency mutation found in MRL-lpr" Lab Anim Sci. 42. 211-213 (1992)
[Publications] Sasaoka,T: "Analysis of the human tyrosine hydroxylase promoter-chloramphenicol acetyltransferase chimeric gene expression in transgenic mice" Mol Brain Res. 16. 274-286 (1992)
[Publications] Matsuba,T: "Genomic analysis of Theileria sergenti stocks in Japan with DNA probes" Vet Parasito. 41. 35-43 (1992)
[Publications] Ishii,M: "Activation of bovine peripheral blood monocyte and its suppressive effect on parasitemia in Theileria sergenti infected calves" J Vet Med Sci. 54. 473-477 (1992)
[Publications] Onuma,M: "Infection and dysfunction of monocytes induced by experimental inoculation of calves with bovine immunodeficiency-like virus" J AIDS. 5. 1009-1015 (1992)
[Publications] Kirisawa,R: "The genomic diversity among equine herpesvirus-1 strains isolated in Japan" Arch Virol.
[Publications] Inazu,M: "Equid herpesvirus 1 infection in mice" J Vet Med Sci.
[Publications] Miyoshi,I: "Useful short-range transport of mouse embryos by means of a nonfreezing technique" Lab Anim Sci. 42. 198-201 (1992)
[Publications] Miyoshi,I: "A practical transport system for mouse embryos cryopreserved by simple vitrification" Lab Anim Sci. 42. 323-325 (1992)
[Publications] Kasai,M: "High survival of rabbit morulae after vitrification in an ethylene glycol-based solution by a simple method" Biol Reprod. 46. 1042-1046 (1992)
[Publications] Kasai,M: "Survival of mouse morulae vitrified in an ethylene glycol-based solution after exposure to the solution at various temperatures" Biol Reprod. 47. 1134-1139 (1992)
[Publications] Tachikawa,S: "Successful vitrification of bovine blastocysts,derived by in vitro maturation and fertilization" Mol Reprod Dev.
[Publications] Koike,S: "A second gene for the African green monkey poliovirus receptor that has no putative N-glycosylation site in the functional N-terminal immunoglobulin-like domain" J Virol. 66. 7059-7066 (1992)
[Publications] Koike,S: "Poliovirus-sensitive transgenic mice as a new animal model" Dev Biol Stand.
[Publications] Satokata,I: "Three nonsense mutations responsible for group A xeroderma pigmentosum" Mutat Res. 273. 193-202 (1992)
[Publications] Satokata,I: "Identification of splicing mutations of the last nucleotides of exons,a nonsense mutation,and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum" Mutat Res. 273. 203-212 (1992)
[Publications] Tanaka,K: "Conference report:Joint workshop on DNA repair mechanisms and embryo menipulation" Mutat Res. 273. 237-241 (1992)
[Publications] Satokata,I: "Molecular basis of group A xeroderma pigmentosum:a missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene" Hum Genet. 88. 603-607 (1992)
[Publications] Miyamoto,I: "Mutational analysis of the structure and function of the xeroderma pigmentosum group A complementing protein" J Biol Chem. 267. 12182-12187 (1992)
[Publications] Eker,APM: "Xeroderma pigmentosum group A correcting protein from calf thymus" Mutat Res. 274. 211-224 (1992)
[Publications] Mimaki,T: "Allelic heterogeneity in group A xeroderma pigmentosum" Acta Neurol Scand. 85. 327-330 (1192)
[Publications] Masutani,C: "Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts" J Biol Chem.
[Publications] Nakagata,N: "High fertilizing ability of mouse spermatozoa diluted slowly after cryopreservation" Theriogenology. 37. 1283-1291 (1992)
[Publications] Nakagata,N: "Production of normal young following insemination of frozen-thawed mouse spermatozoa into Fallopian tubes of pseudopregnant females" Exp Anim. 41. 519-522 (1992)
[Publications] Tomomura,M: "Abnormal expression of urea cycle enzyme genes in juvenile visceral steatosis (jvs) mice" Biochim Biophys Acta. 1138. 167-171 (1992)
[Publications] Horiuchi,M: "Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of urea cycle enzymes by normalizing their transcription" J Biol Chem. 267. 5032-5035 (1992)
[Publications] Hirotsune,S: "New approach for detection of amplification in cancer DNA using restriction landmark genomic scanning" Cancer Res. 52. 3642-3647 (1992)
[Publications] Hayashizaki,Y: "A new method for constructing Not I linking and boundary libraries using a restriction trapper" Genomics. 14. 733-739 (1992)
[Publications] Hayashizaki,Y: "Restriction landmark genomic scanning method and its various applications" Changing derection in DNA electrophoresi.

1992 Fiscal Year Annual Research Report

野生遺伝子および外来遺伝子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 (財)実験動物中央研究所, 所長 (10072399)

Research Products

[Publications] Kobayashi,K: "Genetic alteration of catecholamine specificity in transgenic mice" Proc Natl Acad Sci USA. 89. 1631-1635 (1992)

[Publications] Ito,M: "Preservation of an inbred mouse strain by the storage of frozen embryos:An estimate of the time of occurrence of a serum lgG1 deficiency mutation found in MRL-lpr" Lab Anim Sci. 42. 211-213 (1992)

[Publications] Sasaoka,T: "Analysis of the human tyrosine hydroxylase promoter-chloramphenicol acetyltransferase chimeric gene expression in transgenic mice" Mol Brain Res. 16. 274-286 (1992)

[Publications] Matsuba,T: "Genomic analysis of Theileria sergenti stocks in Japan with DNA probes" Vet Parasito. 41. 35-43 (1992)

[Publications] Ishii,M: "Activation of bovine peripheral blood monocyte and its suppressive effect on parasitemia in Theileria sergenti infected calves" J Vet Med Sci. 54. 473-477 (1992)

[Publications] Onuma,M: "Infection and dysfunction of monocytes induced by experimental inoculation of calves with bovine immunodeficiency-like virus" J AIDS. 5. 1009-1015 (1992)

[Publications] Kirisawa,R: "The genomic diversity among equine herpesvirus-1 strains isolated in Japan" Arch Virol.

[Publications] Inazu,M: "Equid herpesvirus 1 infection in mice" J Vet Med Sci.

[Publications] Miyoshi,I: "Useful short-range transport of mouse embryos by means of a nonfreezing technique" Lab Anim Sci. 42. 198-201 (1992)

[Publications] Miyoshi,I: "A practical transport system for mouse embryos cryopreserved by simple vitrification" Lab Anim Sci. 42. 323-325 (1992)

[Publications] Kasai,M: "High survival of rabbit morulae after vitrification in an ethylene glycol-based solution by a simple method" Biol Reprod. 46. 1042-1046 (1992)

[Publications] Kasai,M: "Survival of mouse morulae vitrified in an ethylene glycol-based solution after exposure to the solution at various temperatures" Biol Reprod. 47. 1134-1139 (1992)

[Publications] Tachikawa,S: "Successful vitrification of bovine blastocysts,derived by in vitro maturation and fertilization" Mol Reprod Dev.

[Publications] Koike,S: "A second gene for the African green monkey poliovirus receptor that has no putative N-glycosylation site in the functional N-terminal immunoglobulin-like domain" J Virol. 66. 7059-7066 (1992)

[Publications] Koike,S: "Poliovirus-sensitive transgenic mice as a new animal model" Dev Biol Stand.

[Publications] Satokata,I: "Three nonsense mutations responsible for group A xeroderma pigmentosum" Mutat Res. 273. 193-202 (1992)

[Publications] Satokata,I: "Identification of splicing mutations of the last nucleotides of exons,a nonsense mutation,and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum" Mutat Res. 273. 203-212 (1992)

[Publications] Tanaka,K: "Conference report:Joint workshop on DNA repair mechanisms and embryo menipulation" Mutat Res. 273. 237-241 (1992)

[Publications] Satokata,I: "Molecular basis of group A xeroderma pigmentosum:a missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene" Hum Genet. 88. 603-607 (1992)

[Publications] Miyamoto,I: "Mutational analysis of the structure and function of the xeroderma pigmentosum group A complementing protein" J Biol Chem. 267. 12182-12187 (1992)

[Publications] Eker,APM: "Xeroderma pigmentosum group A correcting protein from calf thymus" Mutat Res. 274. 211-224 (1992)

[Publications] Mimaki,T: "Allelic heterogeneity in group A xeroderma pigmentosum" Acta Neurol Scand. 85. 327-330 (1192)

[Publications] Masutani,C: "Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts" J Biol Chem.

[Publications] Nakagata,N: "High fertilizing ability of mouse spermatozoa diluted slowly after cryopreservation" Theriogenology. 37. 1283-1291 (1992)

[Publications] Nakagata,N: "Production of normal young following insemination of frozen-thawed mouse spermatozoa into Fallopian tubes of pseudopregnant females" Exp Anim. 41. 519-522 (1992)

[Publications] Tomomura,M: "Abnormal expression of urea cycle enzyme genes in juvenile visceral steatosis (jvs) mice" Biochim Biophys Acta. 1138. 167-171 (1992)

[Publications] Horiuchi,M: "Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of urea cycle enzymes by normalizing their transcription" J Biol Chem. 267. 5032-5035 (1992)

[Publications] Hirotsune,S: "New approach for detection of amplification in cancer DNA using restriction landmark genomic scanning" Cancer Res. 52. 3642-3647 (1992)

[Publications] Hayashizaki,Y: "A new method for constructing Not I linking and boundary libraries using a restriction trapper" Genomics. 14. 733-739 (1992)

[Publications] Hayashizaki,Y: "Restriction landmark genomic scanning method and its various applications" Changing derection in DNA electrophoresi.

野村達次 (財)実験動物中央研究所, 所長 (10072399)