1997 Fiscal Year Annual Research Report

多因子遺伝病の研究:宿主

Research Project

Project/Area Number	09307004
Research Category	Grant-in-Aid for Scientific Research (A)
Research Institution	Kyoto University
Principal Investigator	日合弘京都大学, 医学研究科, 教授 (10073131)
Co-Investigator(Kenkyū-buntansha)	石本秋稔京都大学, ウイルス研, 教授 (50073127) 阿不江ぱ塔爾京都大学, 医学研究科, 助手 (60293875) 賀本敏行京都大学, 医学研究科, 助手 (00281098) 豊國伸哉京都大学, 医学研究科, 講師 (90252460) 福本学京都大学, 医学研究科, 助教授 (60156809)
Keywords	Pre B リンパ腫 / 肺癌感受性遺伝子 / 膀胱癌 / lprマウス / ナカノカタラクト / 腎形成不全
Research Abstract	多くの疾病は宿主の遺伝的組み立てにより、発病の有無、病型、病態、発病時期などが決定されるいわゆる多因子遺伝病である。本年度は次の6つの多因子遺伝病のモデルについて、下記の成果を得た。 (1)SL/KhマウスはPre-Bリンパ腫を高率に発生するが、リンパ腫の発生に先立ち骨髄でポリクローナルなpre-B細胞の増殖をみる。この増殖を示さないNFS/Nとの交配により、その責任遺伝子Pbex1を第3染色体上に同定し、候補遺伝子LEF1の発現、構造について研究を進めている。 (2)肺腫瘍感受性のA/Jと抵抗性のSM/Jの間で組み立てられた26系統の組み換え近交系SMXAマウスの肺腫瘍発生率データをもとにし、RI系間の交配により優性抵抗性遺伝子Par1およびPar2を定量的形質遺伝子として同定した。 (3)ラットの2段階膀胱発癌モデルでは腫瘍プロモーターsodium ascorbateに対する感受性について感受性F344と抵抗性WS系は著差を示した。両系の交配系についてプロモーター感受性の遺伝解析を行い、プロモーター感受性を決定している遺伝子を同定した。 (4)Fas遺伝子の変異に基づくMRL-lpr/lprマウスにみられるリンパ増殖性病変、腎炎、血管炎などの一連の自己免疫病のスペクトラムの決定に宿主側要因がどのように関与するかを、lpr congenic系間の交配系の解析により明らかにした。 (5)ナカノカタラクト(nct)はマウスの先天的劣性カタラクトである。野生由来近交系MSM系との退交配系の遺伝解析によりその遺伝子を染色体上に第16染色体にマップした。 (6)近交系DDSK系マウスでは一側あるいは両側の腎形成不全をみる。我々はこの発生機構は後腎中胚葉組織への尿管芽の進入不全により腎原基がアポトーシスにより吸収されることによることを見出した。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Hiai H.: "Geneti jnedispo sitin to lmrphouas in uie" Pathol,Tntun. 46. 707-718 (1996)
[Publications] Suwa,H.: "Oveuxmessin of the rhoc gene colati with mogursin of ductal adinocaicinuwa of the panaeas" Biit J.Caucn. 77. 147-152 (1998)
[Publications] Tanuma T.: "Owantitatuie ttait loci affe ctihg 4NCao-inauced tingue caacirogeuesis in the rat." Canw Res. in press. (1998)
[Publications] Hiai H.: "Mapping of Nakano cataract gune nct on nwure chumes some 16." Genonics. in press. (1998)
[Publications] Lu-LM.: "Furthu chara itui3 atuin of LEXF R1 setauis of rats" in press. (1998)
[Publications] Lu,L-M.: "Lays gauular lepuplw ati lepuphomas d+aeliping in Hume ctonujed (SLAci XAKR)F_1 mice" Amu,J,rathol.in press. (1998)
[Publications] Shisa H., et al.: "A new set of rat recombinaut iubud straius between LE/Stm and F344." Mammal.Gerwme. 8. 324-327 (1997)
[Publications] Toyokuni,S., et al.: "Quantitative irunuro histo chemical deteruiratin of 8-bydcoxy 2′-deoxyguanosiu by a monocbonal auti body N45.1." Lab Fuvest.76. 365-374 (1997)
[Publications] Kamoto,T.et al.: "Quautitative trait loci associated aith prouoting effets of sodium L-ascorbate on two stage bladder carciuogeueis in rats." Jpn.J.Cancer Res.88. 633-638 (1997)
[Publications] Abujiang,P., et al.: "Geneti resis bewe to urethaue induced puluronay aderumas in SMXA R1 stains." Caucr Res.57. 2904-2908 (1997)
[Publications] Wang.bf., et al.: "Host modifier geres affecting movse autuirumuring indecee by Lpr gene." Ainer.J,Pathol. 151. 1791-1798 (1997)
[Publications] Tanaka,T: "9nowctius ofnd nuclear trauslocatin of thiosedoxin by oxidatine damage in the uioare kidney : indupenonce of tubular necrosi and sulfhydryl defletin" Lab.Fuvest.77. 145-155 (1997)
[Publications] Iida F, et al.: "Rupture of leus cataraot = A novel hereditary recessive cataract moael in the neouse." Exp. Eye Res.64. 107-113 (1997)
[Publications] Hattori,Y., et al.: "8-hydroxy-2′-deoxyguanosine is increased in epiaermal ueles of hairless mice after chunic ultrariolit B exposure." Mvest.Derwatol.107. 733-737 (1997)
[Publications] Higo,K.et al.: "Suocepeibility of nude ruio carrying the FN-4gene to Frience murine laubenia virus in duction" T.Virol. 71. 750-754 (1997)
[Publications] Lu,L-M.et al.: "Expression of LECAM-1 and LFA-1 on pre-B lymphoma cells but not on preneoplastic preB cells in SL/Kh mice." Leuk,Res.21. 337-342 (1997)
[Publications] Toyokuni,S., et al.: "Induction of a wide rauge of C2-12 aldihydi and C17-12 aujloius in the kianey of Wistar rats after tieatment cutik a renal" Frce Rad.Biol.Med.22. 1019-1027 (1997)
[Publications] Nishiyama,Y.et al.: "Overexpression of iutegrin-associatcd proteri(CD47)in rat kidney treatid uictl a revel carcinogeu,fevric vitrilo a cetate" Jpn.J.Caucer Res.88. 120-128 (1997)

1997 Fiscal Year Annual Research Report

多因子遺伝病の研究:宿主

Principal Investigator

日合 弘 京都大学, 医学研究科, 教授 (10073131)

Research Products

[Publications] Hiai H.: "Geneti jnedispo sitin to lmrphouas in uie" Pathol,Tntun. 46. 707-718 (1996)

[Publications] Suwa,H.: "Oveuxmessin of the rhoc gene colati with mogursin of ductal adinocaicinuwa of the panaeas" Biit J.Caucn. 77. 147-152 (1998)

[Publications] Tanuma T.: "Owantitatuie ttait loci affe ctihg 4NCao-inauced tingue caacirogeuesis in the rat." Canw Res. in press. (1998)

[Publications] Hiai H.: "Mapping of Nakano cataract gune nct on nwure chumes some 16." Genonics. in press. (1998)

[Publications] Lu-LM.: "Furthu chara itui3 atuin of LEXF R1 setauis of rats" in press. (1998)

[Publications] Lu,L-M.: "Lays gauular lepuplw ati lepuphomas d+aeliping in Hume ctonujed (SLAci XAKR)F_1 mice" Amu,J,rathol.in press. (1998)

[Publications] Shisa H., et al.: "A new set of rat recombinaut iubud straius between LE/Stm and F344." Mammal.Gerwme. 8. 324-327 (1997)

[Publications] Toyokuni,S., et al.: "Quantitative irunuro histo chemical deteruiratin of 8-bydcoxy 2′-deoxyguanosiu by a monocbonal auti body N45.1." Lab Fuvest.76. 365-374 (1997)

[Publications] Kamoto,T.et al.: "Quautitative trait loci associated aith prouoting effets of sodium L-ascorbate on two stage bladder carciuogeueis in rats." Jpn.J.Cancer Res.88. 633-638 (1997)

[Publications] Abujiang,P., et al.: "Geneti resis bewe to urethaue induced puluronay aderumas in SMXA R1 stains." Caucr Res.57. 2904-2908 (1997)

[Publications] Wang.bf., et al.: "Host modifier geres affecting movse autuirumuring indecee by Lpr gene." Ainer.J,Pathol. 151. 1791-1798 (1997)

[Publications] Tanaka,T: "9nowctius ofnd nuclear trauslocatin of thiosedoxin by oxidatine damage in the uioare kidney : indupenonce of tubular necrosi and sulfhydryl defletin" Lab.Fuvest.77. 145-155 (1997)

[Publications] Iida F, et al.: "Rupture of leus cataraot = A novel hereditary recessive cataract moael in the neouse." Exp. Eye Res.64. 107-113 (1997)

[Publications] Hattori,Y., et al.: "8-hydroxy-2′-deoxyguanosine is increased in epiaermal ueles of hairless mice after chunic ultrariolit B exposure." Mvest.Derwatol.107. 733-737 (1997)

[Publications] Higo,K.et al.: "Suocepeibility of nude ruio carrying the FN-4gene to Frience murine laubenia virus in duction" T.Virol. 71. 750-754 (1997)

[Publications] Lu,L-M.et al.: "Expression of LECAM-1 and LFA-1 on pre-B lymphoma cells but not on preneoplastic preB cells in SL/Kh mice." Leuk,Res.21. 337-342 (1997)

[Publications] Toyokuni,S., et al.: "Induction of a wide rauge of C2-12 aldihydi and C17-12 aujloius in the kianey of Wistar rats after tieatment cutik a renal" Frce Rad.Biol.Med.22. 1019-1027 (1997)

[Publications] Nishiyama,Y.et al.: "Overexpression of iutegrin-associatcd proteri(CD47)in rat kidney treatid uictl a revel carcinogeu,fevric vitrilo a cetate" Jpn.J.Caucer Res.88. 120-128 (1997)

日合弘京都大学, 医学研究科, 教授 (10073131)