1994 Fiscal Year Annual Research Report

胸腺腫発生遺伝子Tsr-1の分子生物学的研究

Research Project

Project/Area Number	06280213
Research Institution	Nagoya University
Principal Investigator	松山睦司名古屋大学, 医学部, 教授 (80073112)
Co-Investigator(Kenkyū-buntansha)	加藤秀樹実験動物中央研究所, 遺伝研究室, 室長 (30142053) 吉田松年名古屋大学, 医学部, 教授 (70090420) 佐賀信介名古屋大学, 医学部, 助教授 (40144141)
Keywords	胸腺腫発生遺伝子 / Tsr-1 / 胸腺増大遺伝子 / Ten-1 / Ten-2 / 胸腺サイズ抑制遺伝子
Research Abstract	我々は、ホト胸腺腫と全く類似の形態を示す上皮性胸腺腫をほぼ全例に自然発生させる近交系ラットBUF/Mnaを樹立し、維持している。この胸腺腫発生は単一の優性遺伝子Tsr-1により統御されており、その発現の場は胸腺上皮細胞であることを明らかにした。本系ラットには胸腺腫発生以前に胸腺真性過形成が100%に発生し、その過形成胸腫の中に胸腺腫小結節が発生して来ることが確認された。遺伝学的検索から、この胸腺真性過形成の発生は、優性胸腺増大遺伝子Ten-1およびTen-2によって統御されていることを実証した。このTen-1またはTen-2のいずれかが胸腺腫発生遺伝子Tsr-1と同一遺伝子である可能性が非常に高いと予想されるので、まず両遺伝子のmappingを行い、いずれがTsr-1であるかを判定する。 1.Ten-1およびTen-2の分子遺伝学的解析:6週令の{(WKY X BUF/Mna)F1 X BUF/Mna}退交配ラットの脾組織より長鎖DNAを抽出し、297個のラットおよび73個のマウスmicrosatellite markerと4個のRFLP probeを用いてPCR法およびRFLP法解析による多型をtypingし、胸腺サイズとの連鎖解析を行った。Ten-1は第1染色体に位置するD1Mgh11遺伝子の4cM近位に、Ten-2は第13染色体に位置するD13N2遺伝子の5cM近位に存在していた。上記退交配ラットのD1Mgh11およびD13N2遺伝子のgenotypeと胸腺サイズとの相関関係を検索したところ、Ten-1はTen-2に比し、胸腺増大能が高かった。また、第3染色体に位置するMIT-R244とMIT-R593遺伝子の間に、胸腺サイズ増大を抑制する遺伝子が存在することも明らかになった。 2.Ten-1およびTen-2遺伝子導入コンジェニックラットの樹立:両遺伝子を退交配法により胸腺腫嫌発系のWKY系ラットに導入したcongenic rat(WKY-Ten-1/Ten-1-Ten-2/Ten-2)を樹立するため、退交配を繰り返し14代に達している。Ten-1及びTen-2遺伝子とPCR marker(D1Mgh11およびD13N2)との連関を指標として、両遺伝子保有を想定されるラットを検出し、退交配の効率化と迅速化を実現した。今年度の研究により、Ten-1に4cM、及びTen-2に5cMに迫ることが出来た。現在BUF/Mna系と野性由来の純系ラットMITEとの退交配ラット、及びマウス用に開発された約4000のmarkerの中、ラットに有用で多型を示すものを選び、両遺伝子に1cM以内に迫りたい。これらの遺伝子とcongenic ratを活用して、YAC法またはウォーキング法で両遺伝子をクローニングし、Tsr-1との異同を明らかにしたい。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Yoshiki Murakumo: "Linkage of the athymic nude locus with myeloperoxidase locus in the rat." Pathology International. 45(in press). (1995)
[Publications] Naoya Asai: "Mechanism of activation of the ret prote-oncogene by multiple endocrine neoplasia 2A mutations." Mol.Cell.Biol.15. 1613-1619 (1995)
[Publications] Osamu Miyaishi: "Age-related attenuation of HSP47 heat response in fibroblasts." Mech.Ageing Dev.77. 213-226 (1995)
[Publications] Shoichi Maruyama: "Germ line mutaions of the ret prote-oncogene in Japanese patients with multiple endocrine neoplasia type 2A and type 2B." Jpn.J.Cancer Res.85. 879-882 (1995)
[Publications] Sumiko Hyuga: "Autocrine factor enhancing the secretion of Mr 95,000 gelatinase (matrix metalloproteinase 9) in serum-free medium conditioned with murine metastatic colon carcinoma cells." Cancer Res.54. 3611-3616 (1994)
[Publications] Takayuki Sakurai: "The ter primordial germ cell deficiency mutation maps near Grl-1 on mouse chromosome 18." Mammalian Genome. 5. 333-336 (1994)
[Publications] Ken-ichi Kozaki: "Tissue distribution of ERp61 and association of its increased expression with IgG production in hybridoma cells." Exp.Cell Res.213. 348-358 (1994)
[Publications] Toyonori Tsuzuki: "Spatial and temporal expression of the ret proto-oncogene product in embryonic,infant and adult rat tissues." Oncogene. 10. 191-198 (1994)
[Publications] Takeshi Sakurai: "Anti-oncogene product p53 binds DNA helicase." Exp.Cell Res.215. 57-62 (1994)
[Publications] Shonen Yoshida: "Interaction of poly (ADP-ribose) lpolymerase with DNA polymerase α." Mol.Cell.Biochem.138. 39-44 (1994)
[Publications] Masahiko Asano: "Purification and characterization of nuclear phospholipase C specific for phosphoinositides." J.Biol.Chem.269. 12360-12366 (1994)
[Publications] Cynthia M.G.Simbulan: "Sulphate-and sialic acid-containing glycolipids inhibit DNA polymerase α activity." Biochim.Biopys.Acta. 1205. 68-74 (1994)
[Publications] Cynthia M.G.Simbulan: "Sphingosine inhibits the synthesis of RNA primers by primase in vitro." Biochemistry. 33. 9007-9012 (1994)
[Publications] Hideki Katoh: "Segmental tetrasomy of chromosome 12 in the mouse." Cytogenet.Cell Genet.67. 27-30 (1994)
[Publications] Hitoshi Horie: "Transgenic mice carry the human poliovirus receptor:New animal model for study of poliovirus neurovirulence." J.Virol.68. 681-688 (1994)
[Publications] Yasuo yamashita: "Rapid degradation of the heavy chain of class I major histocompatibility complex antigens in the endoplasmic reticulum of human cytomegalovirus-infected cells." J.Virol.68. 7933-7943 (1994)
[Publications] Hideki Suzuki: "Internal biliary drainage,unlike external drainage,does not suppress the regeneration of cholestatic rat liver after partial hepatectomy." Hepatology. 20. 1318-1322 (1994)
[Publications] Toyofumi Yamaguchi: "Synthenic nucleosides and nucleotides.XXXI.Inhibitiory effectes of 2'-deoxy-5-styryluridine 5'-triphosphate analogues on retroviral reverse transcriptases and higher eukaryotic DNA polymerases." Nucleosides & Nucleotides. 13. 1247-1258 (1994)
[Publications] Akira Masuda: "Epithelial cel lines from a rat thymoma and a rat thymus. In Cells and Tissue." John Wiley and Sons (in), (1995)
[Publications] Hideki Katoh: "Genetic profile wild derived inbred strains maintained and preserved in Japan. In Genetics in Wild Mice-Applications for Biomedical Research-." Karger, 15 (1994)

1994 Fiscal Year Annual Research Report

胸腺腫発生遺伝子Tsr-1の分子生物学的研究

Principal Investigator

松山 睦司 名古屋大学, 医学部, 教授 (80073112)

Research Products

[Publications] Yoshiki Murakumo: "Linkage of the athymic nude locus with myeloperoxidase locus in the rat." Pathology International. 45(in press). (1995)

[Publications] Naoya Asai: "Mechanism of activation of the ret prote-oncogene by multiple endocrine neoplasia 2A mutations." Mol.Cell.Biol.15. 1613-1619 (1995)

[Publications] Osamu Miyaishi: "Age-related attenuation of HSP47 heat response in fibroblasts." Mech.Ageing Dev.77. 213-226 (1995)

[Publications] Shoichi Maruyama: "Germ line mutaions of the ret prote-oncogene in Japanese patients with multiple endocrine neoplasia type 2A and type 2B." Jpn.J.Cancer Res.85. 879-882 (1995)

[Publications] Sumiko Hyuga: "Autocrine factor enhancing the secretion of Mr 95,000 gelatinase (matrix metalloproteinase 9) in serum-free medium conditioned with murine metastatic colon carcinoma cells." Cancer Res.54. 3611-3616 (1994)

[Publications] Takayuki Sakurai: "The ter primordial germ cell deficiency mutation maps near Grl-1 on mouse chromosome 18." Mammalian Genome. 5. 333-336 (1994)

[Publications] Ken-ichi Kozaki: "Tissue distribution of ERp61 and association of its increased expression with IgG production in hybridoma cells." Exp.Cell Res.213. 348-358 (1994)

[Publications] Toyonori Tsuzuki: "Spatial and temporal expression of the ret proto-oncogene product in embryonic,infant and adult rat tissues." Oncogene. 10. 191-198 (1994)

[Publications] Takeshi Sakurai: "Anti-oncogene product p53 binds DNA helicase." Exp.Cell Res.215. 57-62 (1994)

[Publications] Shonen Yoshida: "Interaction of poly (ADP-ribose) lpolymerase with DNA polymerase α." Mol.Cell.Biochem.138. 39-44 (1994)

[Publications] Masahiko Asano: "Purification and characterization of nuclear phospholipase C specific for phosphoinositides." J.Biol.Chem.269. 12360-12366 (1994)

[Publications] Cynthia M.G.Simbulan: "Sulphate-and sialic acid-containing glycolipids inhibit DNA polymerase α activity." Biochim.Biopys.Acta. 1205. 68-74 (1994)

[Publications] Cynthia M.G.Simbulan: "Sphingosine inhibits the synthesis of RNA primers by primase in vitro." Biochemistry. 33. 9007-9012 (1994)

[Publications] Hideki Katoh: "Segmental tetrasomy of chromosome 12 in the mouse." Cytogenet.Cell Genet.67. 27-30 (1994)

[Publications] Hitoshi Horie: "Transgenic mice carry the human poliovirus receptor:New animal model for study of poliovirus neurovirulence." J.Virol.68. 681-688 (1994)

[Publications] Yasuo yamashita: "Rapid degradation of the heavy chain of class I major histocompatibility complex antigens in the endoplasmic reticulum of human cytomegalovirus-infected cells." J.Virol.68. 7933-7943 (1994)

[Publications] Hideki Suzuki: "Internal biliary drainage,unlike external drainage,does not suppress the regeneration of cholestatic rat liver after partial hepatectomy." Hepatology. 20. 1318-1322 (1994)

[Publications] Toyofumi Yamaguchi: "Synthenic nucleosides and nucleotides.XXXI.Inhibitiory effectes of 2'-deoxy-5-styryluridine 5'-triphosphate analogues on retroviral reverse transcriptases and higher eukaryotic DNA polymerases." Nucleosides & Nucleotides. 13. 1247-1258 (1994)

[Publications] Akira Masuda: "Epithelial cel lines from a rat thymoma and a rat thymus. In Cells and Tissue." John Wiley and Sons (in), (1995)

[Publications] Hideki Katoh: "Genetic profile wild derived inbred strains maintained and preserved in Japan. In Genetics in Wild Mice-Applications for Biomedical Research-." Karger, 15 (1994)

松山睦司名古屋大学, 医学部, 教授 (80073112)