1991 年度実績報告書

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

研究課題

研究課題/領域番号	03206104
研究機関	(財)実験動物中央研究所
研究代表者	野村達次 (財)実験動物中央研究所, 所長 (10072399)
研究分担者	林崎良英国立循環器病センター研究所, バイオサイエンス部, 研究員 (70192705) 早川純一郎金沢大学, 医学部, 助教授 (50110622) 中潟直己日本生物科学研究所, 第5部, 研究員 (30159058) 葛井孫三郎高知大学, 農学部, 助教授 (60152617) 岩井浤酪農学園大学, 酪農学部・獣医学科, 教授 (00072405)
キーワード	胚操作 / 凍結保存 / ポリオウイルス受容体 / トランスジェニックマウス / ジ-ンタ-ゲッティング / ゲノムスキャンニング / 色素性乾皮症 / ヒト疾患モデル
研究概要	本研究は胚操作法を駆使して得られる遺伝子導入動物および近年新しい展開をみせつつある野生集団から近交系への遺伝子の導入によって作られた実験動物を,導入遺伝子の安定性を確かめながら動物実験に供給できるようになるまでのシステムを総合的に研究しようとするものである。そのためには,胚や配偶子の凍結保存,微生物や遺伝子のモニタリングシステムなど研究を支援するような研究開発にも力を入れる必要がある。これらの研究支援的研究はきわめて進展し,マウスを個体で維持する必要はなくなり,胚や配偶子の状態で液体チッ素で凍結しておくことができるようになった。その結果,スペ-スや労力が節約できるだけでなく,計画的に日時および量を決めて産仔を得ることが可能となった。このため,輸送も簡便で,一時に大量の個体を使った実験ができる。生物機能モデルおよびヒト疾患モデルとしては,ポリオウイルス受容体導入マウスがポリオウイルスに感受性であることが確かめられ,ヒトやサルにしか感染しなかったポリオウイルスをトランスジェニックマウスを使って感染症を研究できる道が開かれた。また色素性乾皮症(XP)の原因となる遺伝子(XPAC)を単離した後,この遺伝子を標的としてジ-ンタ-ゲッティングを行ったところ,紫外線に感受性の細胞を作ることができ,現在キメラマウスを作成したところである。このマウスからXPA欠損マウスが得られれば,皮膚がん発症のモデルとなることが期待できる。様々なモデルマウスを作るにも,まず遺伝子を同定し,地図を作ることが第一歩である。そこで本研究班では,ゲノムスキャンニング法の確立を行ない成功した。現在マウス遺伝子のうち約1000個のRFLP断片を得ることができた。以上のように今年度は,著しい成果が得られ,生物機能モデルおよびヒト疾患モデルの開発に目途をつけることができた。

研究成果
(28件)

すべてその他

すべて文献書誌 (28件)

[文献書誌] Kagiyama N: "Microbiological monitoring program of the ICLAS Monitoring Center(Asia)" In Proceedings,The 14th Seminar on Science and TechnologyーLaboratory Animalsー. 83-100 (1991)
[文献書誌] Katoh H: "Genetic monitoring system in the ICLAS Coordinating Monitoring Center (Asia)" in proceedings,the 14th Seminar on Science and technologyーLaboratory Animals‐. 467-469 (1991)
[文献書誌] Kaneda N: "Tissue‐specific and high‐level expression of the human tyrosine hydroxylase gene in transgenic mice" Neuron. 6. 583-594 (1991)
[文献書誌] Nagatsu l: "Expression in brain sensory neurons of the transgene in transgenic mice carrying human tyrosine hydroxylase gene" Neuroscience Letters. 127. 91-95 (1991)
[文献書誌] Fukamizu A: "Human renin in transgenic mouse kidney is localized to juxtaglomerular cells" Biochem J. 278. 601-603 (1991)
[文献書誌] Maruo K: "Toxicity of anticancer agents,growth and chemosensitivity of human tumour xenografts in a segregating stock of AF nude mice" Laboratory Animals. 25. 342-347 (1991)
[文献書誌] Shimamto T: "Moleclar cloning of human XPAC gene homologs from chicken,xenopus laevis and drosphila melanogaster" Biochem Biophys Res Comm.
[文献書誌] Satokata l: "Three nonsense mutations responsible for group A xeroderma pigmentosum" Mutation Res.
[文献書誌] Satokata l: "ldentification 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 pigmetosum" Mutation Res.
[文献書誌] Tanaka K: "Joint workshop on DNA repair mechanisms and embryo manipulation" Mutation Res.
[文献書誌] Satokata l: "Milecular basis of group A xeroderma pigmentosum:A missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene" Human Genet.
[文献書誌] Miyamoto l: "Mutational analysis of the structure and function of the XPAC protein:identification of essential domains for nuclear localization and DNA excison repair" J Biol Chem.
[文献書誌] ltoh T: "Comparative lung pathology of inbred strains of mice resistant and susceptible to Sendai virus infection" J Vet Med Sci. 53. 275-279 (1991)
[文献書誌] lshi S: "Bovine peripheral blood monocyte activity and the growth of Theileria sergenti in blood" J Vet Med Sci.
[文献書誌] Matsuba T: "Genomic analysis of theileria sergenti stocks in Japan with DNA probes" Vet Parasitol.
[文献書誌] Miyoshi l: "Useful shortーrange transport of mouse embryos by means of a nonfreezing technique" Lab Anim Sci.
[文献書誌] Kasai M: "High survival of rabbit morulae after vitrification in an ethylene glycol‐based solution by a simple method" Biol Reprod.
[文献書誌] Miura N: "ldentification and characterization of xpac protein,the gene product of the human XPAC(Xeroderma Pigmentosum Group A Complementing)gene" J Biol Chem. 266. 19786-19789 (1991)
[文献書誌] Nakagata N: "Cryopreservation of mouse oocytes and embryos by ultrarapid freezing The 14th Seminar on Science and Technology 1990 Japan‐Taiwan Laboratory" Animals Seminar. 251-268 (1991)
[文献書誌] Aihara S: "ldentification of mutations that occurred on the genome of Japanese encephalitis virus during the attenuation process" Virus Genes. 5. 95-109 (1991)
[文献書誌] Koike S: "Trasgenic mice susceptible to poliovirus" Proc Natl Acad sci USA. 88. 951-955 (1991)
[文献書誌] Tsukiyama‐Kohara K: "A second group of hepatitis C vuruses" Virus Genes. 5. 243-254 (1991)
[文献書誌] Koike S: "Functional domains of the poliovirus receptor" Proc Natl Acad Sci USA. 88. 4104-4108 (1991)
[文献書誌] lizuka N: "Nucleotide sequences important for translation initiation of enterovirus RNA" J Virol. 65. 4867-4873 (1991)
[文献書誌] TsukiyamaーKohara K: "lnternal ribosome entry site wothin hepatitis C vurus RNA" J Virol.
[文献書誌] Nikaido H: "Specificity of the sexーinfluenced esterase(ES‐Sl)isozyme in rat liver" Biochem Genet. 29. 261-269 (1991)
[文献書誌] Koizumi T: "Localization of the gene encoding myelin basic protein to mouse chrome 18E3→4 and rat chromosome 1p11→p12" Cytogene Cell Genet. 56. 199-201 (1991)
[文献書誌] Hatada l: "A genomic scanning method for higher organisms using restiction sites as landmarks" proc Natl Acad Sci USA. 88. 9523-9527 (1991)

1991 年度 実績報告書

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

研究代表者

野村 達次 (財)実験動物中央研究所, 所長 (10072399)

研究成果

[文献書誌] Kagiyama N: "Microbiological monitoring program of the ICLAS Monitoring Center(Asia)" In Proceedings,The 14th Seminar on Science and TechnologyーLaboratory Animalsー. 83-100 (1991)

[文献書誌] Katoh H: "Genetic monitoring system in the ICLAS Coordinating Monitoring Center (Asia)" in proceedings,the 14th Seminar on Science and technologyーLaboratory Animals‐. 467-469 (1991)

[文献書誌] Kaneda N: "Tissue‐specific and high‐level expression of the human tyrosine hydroxylase gene in transgenic mice" Neuron. 6. 583-594 (1991)

[文献書誌] Nagatsu l: "Expression in brain sensory neurons of the transgene in transgenic mice carrying human tyrosine hydroxylase gene" Neuroscience Letters. 127. 91-95 (1991)

[文献書誌] Fukamizu A: "Human renin in transgenic mouse kidney is localized to juxtaglomerular cells" Biochem J. 278. 601-603 (1991)

[文献書誌] Maruo K: "Toxicity of anticancer agents,growth and chemosensitivity of human tumour xenografts in a segregating stock of AF nude mice" Laboratory Animals. 25. 342-347 (1991)

[文献書誌] Shimamto T: "Moleclar cloning of human XPAC gene homologs from chicken,xenopus laevis and drosphila melanogaster" Biochem Biophys Res Comm.

[文献書誌] Satokata l: "Three nonsense mutations responsible for group A xeroderma pigmentosum" Mutation Res.

[文献書誌] Satokata l: "ldentification 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 pigmetosum" Mutation Res.

[文献書誌] Tanaka K: "Joint workshop on DNA repair mechanisms and embryo manipulation" Mutation Res.

[文献書誌] Satokata l: "Milecular basis of group A xeroderma pigmentosum:A missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene" Human Genet.

[文献書誌] Miyamoto l: "Mutational analysis of the structure and function of the XPAC protein:identification of essential domains for nuclear localization and DNA excison repair" J Biol Chem.

[文献書誌] ltoh T: "Comparative lung pathology of inbred strains of mice resistant and susceptible to Sendai virus infection" J Vet Med Sci. 53. 275-279 (1991)

[文献書誌] lshi S: "Bovine peripheral blood monocyte activity and the growth of Theileria sergenti in blood" J Vet Med Sci.

[文献書誌] Matsuba T: "Genomic analysis of theileria sergenti stocks in Japan with DNA probes" Vet Parasitol.

[文献書誌] Miyoshi l: "Useful shortーrange transport of mouse embryos by means of a nonfreezing technique" Lab Anim Sci.

[文献書誌] Kasai M: "High survival of rabbit morulae after vitrification in an ethylene glycol‐based solution by a simple method" Biol Reprod.

[文献書誌] Miura N: "ldentification and characterization of xpac protein,the gene product of the human XPAC(Xeroderma Pigmentosum Group A Complementing)gene" J Biol Chem. 266. 19786-19789 (1991)

[文献書誌] Nakagata N: "Cryopreservation of mouse oocytes and embryos by ultrarapid freezing The 14th Seminar on Science and Technology 1990 Japan‐Taiwan Laboratory" Animals Seminar. 251-268 (1991)

[文献書誌] Aihara S: "ldentification of mutations that occurred on the genome of Japanese encephalitis virus during the attenuation process" Virus Genes. 5. 95-109 (1991)

[文献書誌] Koike S: "Trasgenic mice susceptible to poliovirus" Proc Natl Acad sci USA. 88. 951-955 (1991)

[文献書誌] Tsukiyama‐Kohara K: "A second group of hepatitis C vuruses" Virus Genes. 5. 243-254 (1991)

[文献書誌] Koike S: "Functional domains of the poliovirus receptor" Proc Natl Acad Sci USA. 88. 4104-4108 (1991)

[文献書誌] lizuka N: "Nucleotide sequences important for translation initiation of enterovirus RNA" J Virol. 65. 4867-4873 (1991)

[文献書誌] TsukiyamaーKohara K: "lnternal ribosome entry site wothin hepatitis C vurus RNA" J Virol.

[文献書誌] Nikaido H: "Specificity of the sexーinfluenced esterase(ES‐Sl)isozyme in rat liver" Biochem Genet. 29. 261-269 (1991)

[文献書誌] Koizumi T: "Localization of the gene encoding myelin basic protein to mouse chrome 18E3→4 and rat chromosome 1p11→p12" Cytogene Cell Genet. 56. 199-201 (1991)

[文献書誌] Hatada l: "A genomic scanning method for higher organisms using restiction sites as landmarks" proc Natl Acad Sci USA. 88. 9523-9527 (1991)

1991 年度実績報告書

野村達次 (財)実験動物中央研究所, 所長 (10072399)