੕ହ॥ड़টॠभ໪঩ৎੑਃଡभଢ଼஢॑ஷॉନॊ୕ળ ೦੘叞ળ৛প৾ ৾୒ଢ଼஢੹ ঽேఐ৾৾ୠ᪻⹸ࡢᴫ᪥᫬ィᶵᵓࡢ◊✲ࡣ๓ୡ⣖༙ࡤࡢ⚄⤒࣭ෆศἪᶵᵓࡢ◊✲࡟ጞࡲࡾࠊ⌧ᅾࡢศᏊ⏕≀Ꮫⓗᡭἲ࡟ࡼࡿ◊✲࡬࡜㐍ࢇ࡛ࡁࡓࠋᮏ✏࡛ࡣࠊࡇࢀࡲ࡛࡟ⴭ⪅ࡽࡀ⾜ࡗ࡚ࡁࡓࢥ࢜ࣟࢠࢆ⏝࠸ࡓ᫬ィᶵᵓࡢ◊✲ࢆᴫほࡍࡿࠋ⚄⤒⾜ືᏛⓗ࡞ゎᯒ࠿ࡽࠊࢥ࢜ࣟࢠࡢᴫ᪥᫬ィࡣᕥྑ  ᑐࡢどⴥࡢ /0」ྜయ㸦どⴥᯈʊど㧊㒊ศ㸧࡟࠶ࡾࠊᕥྑࡢどⴥᴫ᪥᫬ィࡣ⚄⤒㊰ࢆ⤒࡚┦஫࡟ྠㄪࡋ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋᴫ᪥᫬ィࡢ᣺ື࡟ࡣ᫬ィ㑇ఏᏊࡢ࿘ᮇⓗⓎ⌧ࡀ㛵ࢃࡿࡀࠊࣁ࢚࡜ྠᵝ࡞ per/timORRS ࡟ຍ࠼࡚ cry2ORRS ࡀྵࡲࢀࡿࠋ᫬ィࡢගྠㄪ࡟ࡣ」║࡛Ⓨ⌧ࡍࡿ⥳ⰍගཷᐜศᏊ 2SVLQ/: ࡀᚲせ࡛࠶ࡾࠊ2SVLQ/: ࠿ࡽࡢ᝟ሗࡣ⚄⤒㊰ࢆ⤒࡚どⴥ᫬ィ࡟ධຊࡉࢀࡿࠋどⴥ᫬ィ࡛ࡢගࣜࢭࢵࢺ࡟ࡣࠊ᫂ᮇ㐜ᘏ᫬࡟ᶵ⬟ࡍࡿ Pdp1 ⣔࡜ᬯ㯮ୗ࡛ගㄏᑟࡉࢀࡿ c-fos/cry ⣔ࡢ  ࡘࡀാ࠸࡚࠸ࡿࠋࡇࢀࡽࡢᬑ㐢ᛶ࡜≉Ṧᛶࡣ⯆࿡῝࠸ㄢ㢟࡛࠶ࡿࠋ
ࡣࡌࡵ࡟ࠕ▼࡟ჶࡾࡘ࠸࡚ࡶࠊ෭ࡸ㣤ࢆ㣗ࡗ࡚ⱞປࡋ࡚࡛ࡶ◊✲⪅࡟࡞ࡾࡓ࠸ࠖ࡜ᛮࡗ࡚࠸ࡓ⚾ࡣࠊ1980 ᖺ 3 ᭶࡟ಟኈㄢ⛬ಟ஢ᚋࠊᖾ࠸࡞ࡇ࡜࡟ᒣཱྀ኱Ꮫ⌮Ꮫ㒊ࡢ༓ⴥ႐ᙪᩍᤵ࡟ຓᡭ࡜ࡋ࡚᥇⏝ࡋ࡚࠸ࡓࡔ࠸ࡓࠋ㏵୰ 1 ᖺవࡾࡢ⡿ᅜ␃Ꮫࢆᣳࢇ࡛ࠊ23 ᖺ㛫ࢆᒣཱྀ኱Ꮫ࡛㐣ࡈࡋࡓࠋᒣཱྀ኱Ꮫ╔௵᫬࡟ࠊ᪻⹸ࡢయෆ᫬ィࡢ⚄⤒ᶵᵓࢆㄪ࡭ࡿ௙஦ࢆ㛤ጞࡋࡓࠋ༓ⴥᩍᤵࡣ⺅ࢆ⏝࠸࡚⾜ືࣜࢬ࣒ࡢ㐺ᛂⓗព⩏࡟㛵ࡍࡿ◊✲ࢆࡉࢀ࡚࠸࡚ࠊ⌮Ꮫ㒊ࡢ᪂タ࡟ࡼࡾ◊✲ᐊࢆᣑ඘ࡍࡿ࡟࠶ࡓࡗ࡚ࠊෆศἪᏛⓗ࡞࢔ࣉ࣮ࣟࢳ࡜⚄⤒⏕⌮Ꮫⓗ࢔ࣉ࣮ࣟࢳࢆᑟධࡋࡼ࠺࡜⪃࠼࡚࠾ࡽࢀࡓࠋࡑࡇ࡛ࠊ᪻⹸ෆศἪᏛࢆᑓ㛛࡜ࡋ࡚࠸ࡓ㐲⸨ඞᙪຓᩍᤵ㸦ᙜ᫬㸧࡜㟁Ẽ⏕⌮Ꮫࢆᑓ㛛࡜ࡋ࡚࠸ࡓ⚾ࡀ᥇⏝ࡉࢀࡿࡇ࡜࡜࡞ࡗࡓࠋᮦᩱࡶᡭἲࡶ⮬⏤࡟Ỵࡵ࡚ࡼ࠸࡜ࡢࡇ࡜࡛࠶ࡗࡓࡢ࡛ࠊᏛ⏕᫬ ௦ ࡟ ౑ ࡗ ࡚ ࠸ ࡓ ࣇ ࢱ ࣍ ࢩ ࢥ ࢜ ࣟ ࢠ 㸦 Gryllus

bimaculatus㸧ࢆᐇ㦂ື≀࡜ࡍࡿࡇ࡜࡟ࡋࡓࠋ᭱ึࡣࠊάືࢆグ㘓ࡍࡿ࡜ࡇࢁ࠿ࡽጞࡵࡓࠋ㏱᫂࡞ࣉࣛࢫࢳࢵ
ࢡࢣ࣮ࢫ㸦⣙ 20×7×6 cm㸧ࡢᗏ㒊࡟ࢩ࣮ࢯ࣮ᘧࡢᗋᯈࢆタ⨨ࡋࡓ࢔ࢡࢺࢢࣛࣇࢆ⮬సࡋࠊ⤊㱋ᗂ⹸ࢆධࢀ
࡚ࠊṌ⾜άືࢆグ㘓ࡋ࡚ࡳࡿ࡜ࠊ᫂ᮇ࡟άືࡀ㧗࠸᫨⾜ᛶࢆ♧ࡋࡓࠋࡋ࠿ࡋࠊ⩚໬ᚋᩘ᪥ࡀ⤒㐣ࡍࡿ࡜ࠊ✺↛ኪ⾜ᛶ࡟㏫㌿ࡍࡿࡇ࡜ࡀศ࠿ࡗࡓ㸦ᅗ 1㸧ࠋࡇࡢࣜ
ࢬ࣒㏫㌿ࡣᜏᬯ᮲௳ୗ࡛ࡶ⏕ࡎࡿෆⓗ࡞ࡶࡢ࡛࠶ࡾࠊ
㞝࡛ࡣㄏᘬḷࡸ⢭ໟస〇ࡢ㛤ጞ࡞࡝ࡢᛶᡂ⇍࡜㌶ࢆ
୍࡟ࡋ࡚⏕ࡎࡿࠋㄏᘬḷࡣࠊ㞝ࢥ࢜ࣟࢠࡀ㞤ࢆㄏᘬࡍ‫ݩ‬tomioka@cc.okayama-u.ac.jp᫬㛫⏕≀Ꮫ㻌㼂㼛㼘㻚㻞㻣㻘㻌㻺㼛㻚㻌㻞㻌㻔㻞㻜㻞㻝㻕㻤㻟ᅗ  ࣇࢱ࣍ࢩࢥ࢜ࣟࢠάືࣜࢬ࣒࡬ࡢどⴥࡢษ㝖ࡢᙳ㡪ࠋࣇࢱ࣍ࢩࢥ࢜ࣟࢠࡣᗂ⹸ᮇ࡟ࡣ᫨⾜ᛶࢆ♧ࡍࡀࠊᡂ⹸⬺⓶㸦LP㸧ᚋᩘ᪥ࢆ⤒࡚ኪ⾜ᛶ࡟㏫㌿ࡍࡿࠋ▮༳ࡢ᫬Ⅼ࡛ᕥྑࡢどⴥࡀษ㝖ࡉࢀࡓࡀࠊどⴥษ㝖ᚋࡣ᏶඲࡟↓࿘ᮇ࡜࡞ࡗࡓࠋグ㘓ࡣ  ᫬㛫᫂㸸 ᫬㛫ᬯࠊΥࡢୗ࡛⾜ࢃࢀࡓࠋάືグ㘓ᅗࡢୖࡢⓑ㯮ࡢࣂ࣮ࡣ᫂(ⓑ㸧ᬯ(㯮㸧ࢆ♧ࡍࠋᅗ  ࢥ࢜ࣟࢠ⚄⤒⣔㸦$㸧࡜どⴥ㸦%㸧࠾ࡼࡧࢦ࢟ࣈࣜどⴥ㸦&㸧ࡢᶍᘧᅗࠋ
どⴥ㸦2/㸧ෆ࡟ࡣ⚄⤒⥺⥔ࡀᐦ࡟ධࡾ⤌ࢇࡔ  ࡘࡢ⚄⤒ྀࡍ࡞ࢃࡕどⴥᯈ㸦/D㸧ࠊど㧊㸦0H㸧
ࠊ๪ど㧊㸦$0H㸧࠾ࡼࡧどᑠⴥ㸦/R㸧ࡀ࠶ࡿࠋどⴥࡣ」║㸦&()࡜ど⚄⤒㸦21㸧࡟ࡼࡾ᥋⥆ࡋࠊどᑠⴥࡣど⚄⤒ᖿ㸦27)ࢆ⤒࡚⬻࡜᥋⥆ࡋ࡚࠸ࡿࠋࢥ࢜ࣟࢠ
࡛ࡣእഃࡢど㧊࡜どⴥᯈ㸦/0」ྜయ㸧ࡀどᑠⴥ࡜㞳ࢀ࡚࠾ࡾࠊ㛗࠸ど᯶㸦26)࡟ࡼࡗ࡚᥋⥆ࡋ࡚࠸ࡿࠋࡿࡓࡵ๓⩟ࢆ᧿ࡾྜࢃࡏ࡚ዌ࡛ࡿࡀࠊㄏᘬḷࡢⓎ㡢⾜㸦lamina㸧ࠊど㧊㸦medulla㸧ࠊどᑠⴥ㸦lobula㸧ࡢ 3ືࡣኪ㛫࡟άⓎ࡟⾜ࢃࢀࡿࡇ࡜࠿ࡽࠊࡇࡢࣜࢬ࣒ࡢኪ

ࡘࡢ⚄⤒ྀ㸦neuropil㸧ࢆྵࡳࠊどᑠⴥ࠿ࡽど⚄⤒ᖿ⾜ᛶ࡬ࡢ㏫㌿ࡣ⏕Ṫάື࡜㛵ಀࡍࡿ࡜⪃࠼ࡽࢀࡿࠋ

࡟ࡼࡾ⬻࡬࡜᥋⥆ࡋ࡚࠸ࡿࠋࢥ࢜ࣟࢠࡢሙྜࡣࠊእഃ

25Υᜏᬯ᮲௳ୗ࡛ࡢ⮬⏤⥅⥆࿘ᮇࡣᗂ⹸ᮇ࡟ࡣ 24 ᫬

ࡢ 2 ࡘࡢ⚄⤒ྀࡀ」║ࡢෆഃ࡟఩⨨ࡋࠊどᑠⴥࡣ⬻࡟㛫ࡼࡾࡶ㛗ࡃࠊᡂ⹸ᮇ࡟ࡣ 24 ᫬㛫ࡼࡾࡶ▷࠸ࠋ୍᪉ࠊ

㏆᥋ࡋࠊど㧊࡜どᑠⴥࡣ㛗࠸ど᯶㸦optic stalk㸧࡜࿧ᜏ᫂᮲௳ୗ࡛ࡣ↓࿘ᮇ࡟࡞ࡿࡶࡢࡶ࠶ࡿࡀࠊࣜࢬ࣒ࢆ

ࡤࢀࡿ⚄⤒࡛㐃⤖ࡋ࡚࠸ࡿ㸦ᅗ 2㸧ࠋࢥ࢜ࣟࢠ࡛ࡣど⥔ᣢࡋࡓࡶࡢ࡛ࡣ࿘ᮇࡣ 24 ᫬㛫ࡼࡾࡶ࠿࡞ࡾ㛗ࡃ࡞ⴥᯈɆど㧊」ྜయ㸦LM 」ྜయ㸧ࢆษ㝖ࡍࡿࡇ࡜࡛Ṍ

ࡗࡓࠋ1982 ᖺ࡟ࡇࢀࡽࡢ⤖ᯝࢆ⧳ࡵ࡚యෆ᫬ィ࡟㛵⾜άືࣜࢬ࣒ࡀᾘኻࡍࡿ㸦ᅗ 1㸧ࡇ࡜࠿ࡽࠊࡇࡢ㒊ศࡍࡿ᭱ึࡢㄽᩥࢆⓎ⾲ࡋࡓ 1ࠋ௨ᚋࠊ40 ᖺ࡟ࢃࡓࡾከ࡟᫬ィࡀᅾࡿࡇ࡜ࡀ♧၀ࡉࢀࡓ 3ࠋࡇ࠺࡞ࡿ࡜ḟ࡟ྲྀࡃࡢᏛ⏕ࡸඹྠ◊✲⪅ࡢ༠ຊࢆᚓ࡚యෆ᫬ィࡢ◊✲ࡾ⤌ࡴ࡭ࡁࡣࠊどⴥ࡟᫬ィࡀᅾࡿࡇ࡜ࢆド᫂ࡍࡿࡇ࡜ࢆ⥆ࡅ࡚ࡁࡓࠋᮏ✏࡛ࡣࠊ≉࡟ࢥ࢜ࣟࢠࡢ᫬ィᶵᵓࢆ࡛࠶ࡗࡓࠋᙜ᫬᪤࡟ࠊInouye ࡜ Kawamura4 ࡟ࡼࡾࠊ୰ᚰ࡟ࡇࢀࡲ࡛ࡢ◊✲ࢆ⧳ࡵࡿࠋᇙࡵ㎸ࡳ㟁ᴟࢆ⏝࠸ࡓ⚄⤒άືࡢ㛗᫬㛫グ㘓ἲ࡟ࡼࡾࠊࣛࢵࢺࡢ SCN ࡀ᫬ィ⤌⧊࡛࠶ࡿࡇ࡜ࡀ♧ࡉࢀ࡚ࢥ࢜ࣟࢠᴫ᪥᫬ィࡢ⚄⤒ᶵᵓ࠸ࡓࠋࡋ࠿ࡋࠊどⴥࡢ⚄⤒άືࢆ㛗᫬㛫グ㘓ࡍࡿࡇ࡜

1980 ᖺᙜ᫬ࠊࡲࡔ᪻⹸࡛ࡣ᫬ィࡢᡤᅾࡣ☜ᐃࡋ࡚ࡣࡑࢀ࡯࡝⡆༢࡛ࡣ࡞࠿ࡗࡓࡢ࡛ࠊ⥙⭷㟁ᅗ㸦ERG㸧

࠾ࡽࡎࠊࡑࡢ᥈✲ࡣᐇ࡟⯆࿡ࢆࡑࡑࡿㄢ㢟࡛࠶ࡗࡓࠋ

ࢆᣦᶆ࡟ࡋ࡚ࠊどⴥࡢእഃ࡟࠶ࡿ」║ࡢឤᗘࣜࢬ࣒ࢆ◊✲ࢆ㐍ࡵࡿ࠺࠼࡛ࡢ㔜せ࡞᝟ሗࡣ 1968 ᖺ࡟ Z.

ㄪ࡭ࡿࡇ࡜࡟ࡋࡓࠋERG ࡢ᣺ᖜࡣ୺ほⓗኪ࡟ቑ኱ࡋࠊvergl. Physiologie ࡟ฟ∧ࡉࢀࡓ Nishiitsutsuji-Uwo᫨పୗࡍࡿࣜࢬ࣒ࢆ♧ࡍࡀࠊࡇࡢࣜࢬ࣒ࡣど᯶ࢆษ᩿࡜ Pittendrigh ࡢㄽᩥ࡛࠶ࡗࡓࠋᙼࡽࡣࠊど⚄⤒ᖿࡋ࡚ LM 」ྜయࢆ⬻࠿ࡽ㝸㞳ࡋ࡚ࡶ⥅⥆ࡍࡿࡇ࡜ࡀ

㸦 optic tract 㸧 ࡢ ษ ᩿ ࡛ ࢦ ࢟ ࣈ ࣜ 㸦 Leucophaeaศ࠿ࡗࡓ㸦ᅗ 3㸧5ࠊ6ࠋmaderae㸧ࡢάືࣜࢬ࣒ࡀᾘኻࡍࡿࡇ࡜ࢆሗ࿌ࡋࠊどࡇ࠺࠸ࡗࡓᐇ㦂ࢆ⥆ࡅ࡚࠸ࡿ࠺ࡕ࡟ࠊ⚄⤒άືࢆ㛗ⴥ࡟᫬ィࡀᅾࡿྍ⬟ᛶࢆᣦ᦬ࡋ࡚࠸ࡓ 2ࠋࡑࡇ࡛ࠊࡲ

᫬㛫࡟ࢃࡓࡗ࡚グ㘓ࡍࡿࡓࡵࡢ‽ഛࢆᩚ࠼ࡿࡇ࡜ࡀࡎࡣどⴥࢆษ㝖ࡋ࡚ࣜࢬ࣒ࡀ࡞ࡃ࡞ࡿࡇ࡜ࢆ☜ㄆࡍ࡛ࡁࡓࡢ࡛ࠊ࠸ࡼ࠸ࡼどⴥ࠿ࡽ㟁Ẽάືࢆグ㘓ࡍࡿᐇࡿࡇ࡜࡟ࡋࡓࠋ᪻⹸ࡢどⴥࡣࠊእഃ࠿ࡽどⴥᯈ㦂࡟╔ᡭࡋࡓࠋࡲࡎࠊど᯶ࢆษ᩿ࡋ࡚྾ᘬ㟁ᴟࢆタ⨨᫬㛫⏕≀Ꮫ㻌㼂㼛㼘㻚㻞㻣㻘㻌㻺㼛㻚㻌㻞㻌㻔㻞㻜㻞㻝㻕㻤㻠ᅗ  ࢥ࢜ࣟࢠ」║ࡢ⥙⭷㟁ᅗ㸦(5*)᣺ᖜࡢᴫ᪥ࣜࢬ࣒ࠋ
グ㘓㛤ጞ᪥ࡢ  ᫬࠿ࡽᜏᬯࠊΥࡢୗ࡟⨨࠿ࢀ࡚࠸ࡿࠋ㯮୸ࡣṇᖖഃࡢࠊⓑ୸ࡣど᯶ษ᩿ഃࡢ」║࠿ࡽグ㘓ࡉࢀࡓ (5* ࣜࢬ࣒ࢆ♧ࡍࠋグ㘓ୖ㒊ࡢⓑࠊࢢ࣮ࣞࠊ㯮Ⰽࡢࣂ࣮ࡣ᫂ᮇ(ⓑ㸧࠾ࡼࡧᜏᬯ⛣⾜๓ࡢ᫂ᮇ㸦ࢢ࣮ࣞ㸧ࠊᬯᮇ(㯮㸧ࢆ♧ࡍࠋ(5*ࡢ᣺ᖜࡣ୺ほⓗኪ࡟ቑ኱ࡋࠊ୺ほⓗ᫨࡟పୗࡍࡿࡀࠊࡇࡢࣜࢬ࣒ࡣど᯶ษ᩿ᚋࡶ⥅⥆ࡍࡿࠋ7RPLRND &KLED ࢆᨵኚࠋᅗ  どⴥ̺」║」ྜయࡢᇵ㣴ୗ࡛ࡢ㟁Ẽάືࡢᴫ᪥ࣜࢬ࣒ࠋ
㸦$㸧࢜࢖ࣝࢠࣕࢵࣉἲ࡟ࡼࡿどⴥ㐲ᚰᛶࢽ࣮ࣗࣟࣥࡢάື㟁఩グ㘓ἲࠋࣉࣛࢫࢳࢵࢡࣉ࣮ࣞࢺࡢ  ࡘࡢ࣮࣍ࣝ࡟ 00 ᇵᆅࢆ‶ࡓࡋࠊࡑࡢ㛫ࡣ࢜࢖࡛ࣝ⤯⦕ࡋࡓࠋ∦ഃࡢᇵᆅ࡟どⴥ̺」║」ྜయࢆධࢀࠊ」ྜయ࠿ࡽᘏࡧࡿど᯶ࢆ཯ᑐഃࡢᇵᆅ࡟࠸ࢀࠊどⴥ࠿ࡽど᯶ࢆ⤒࡚⬻࡬㏦ࡽࢀࡿ㟁Ẽάືࢆグ㘓ࡋࡓࠋ㸦%㸧グ㘓ࡉࢀࡓάື㟁఩ࡢ୍౛ࠋ㸦&㸧どⴥ㟁Ẽάືࡢ㛗᫬㛫グ㘓ࠋ㸴ศ㛫ࡢάື㟁఩ࡢⓎᑕ㢖ᗘࡣኪ㧗ࡃ᫨ప࠸᫂░࡞ᴫ᪥ࣜࢬ࣒ࢆ♧ࡋࡓࠋグ㘓ࡢୖࡢࢢ࣮ࣞ࡜㯮ࡢࣂ࣮ࡣࠊグ㘓๓࡟⨨࠿ࢀ࡚࠸ࡓ᫂㸦ࢢ࣮ࣞ㸧ᬯ㸦㯮㸧࿘ᮇࢆ♧ࡍࠋ ᗘࡣ Υࠋ7RPLRND &KLED ࢆᨵኚࠋࡋࠊ⬻࠿ࡽ㝸㞳ࡋࡓ LM 」ྜయ࠿ࡽ⬻࡬㏦ࡽࢀࡿ⚄⤒㠃ୖ࡟ᾋ࠿࡭ࡡࡤ࡞ࡽ࡞࠸ࠋ᪻⹸ࡢ⚄⤒⣔ࡣẼ⟶ࢆ㏻

άືࢆグ㘓ࡋࡓࠋࡑࡢ⤖ᯝࠊLM 」ྜయࡢ㟁Ẽάືࡣࡋ࡚ࠊ┤᥋࢞ࢫ஺᥮ࢆࡋ࡚࠸ࡿࡓࡵ࡛࠶ࡿࠋᖾ࠸࡟ࡋኪ㛫࡟ቑຍࡋࠊ᫨పୗࡍࡿࣜࢬ࣒ࢆ♧ࡋࠊࡇࡢࣜࢬ࣒

࡚ࠊࡇࡢᡭἲࡣࠊ⡿ᅜ࡛࣏ࢫࢻࢡࢆࡋ࡚࠸ࡿ᫬࡟ࠊࢱ

ࡣᜏᬯࠊᜏ᫂᮲௳ୗ࡛⥅⥆ࡍࡿࡇ࡜ࡀศ࠿ࡾࠊLM 」

ࣂࢥࢫࢬ࣓࢞ࡢ⬻ࡢయእᇵ㣴ᐇ㦂 8 ࡟ᚑ஦ࡍࡿࡇ࡜࡛

ྜయ࡟᫬ィࡀᅾࡿྍ⬟ᛶࡀᙉࡃ♧၀ࡉࢀࡓ 7ࠋ᭱⤊ⓗಟᚓࡍࡿࡇ࡜ࡀ࡛ࡁࡓࠋ㟁Ẽάືࡢグ㘓ἲ࡟ࡘ࠸࡚ࡶࠊ

࡟ LM 」ྜయ࡟᫬ィࡀᅾࡿࡇ࡜ࢆド᫂ࡍࡿ࡟ࡣࠊࡇࡢ

⡿ᅜ␃Ꮫ๓࡟ᙜ᫬ᒣཱྀ኱Ꮫᩍ㣴㒊࡟࠾ࡽࢀࡓᒸᓥ᫛」ྜయࢆయእᇵ㣴ࡋࠊࣜࢬ࣒ࢆ᳨ฟࡍࡿᚲせࡀ࠶ࡗࡓࠋ

ᩍᤵ࠿ࡽࠊ࢜࢖ࣝࢠࣕࢵࣉἲࢆࡈᩍ♧࠸ࡓࡔ࠸ࡓࠋᇵࡇࡢᐇ㦂࡟ࡣࢡࣜ࢔ࡍ࡭ࡁⅬࡀ 2 ࡘ࠶ࡗࡓࠋ୍ࡘࡣࠊ

ᆅ࡟ࡘ࠸࡚ࡣࠊᡭ࡟ධࡿ࠸ࢁ࠸ࢁ࡞ࡶࡢࢆヨࡋ࡚ࡳࡓᇵ㣴⣔ࡢ☜❧࡛ࠊࡶ࠺୍ࡘࡣ㟁Ẽάືࡢグ㘓ἲ࡛࠶ࡿࠋ

ࡀࠊ࡞࠿࡞࠿Ⰻ࠸ࡶࡢࡀぢࡘ࠿ࡽ࡞࠿ࡗࡓࠋࡑࡢࡼ࠺

᪻⹸ࡢ⚄⤒⣔ࡢᇵ㣴࡟ࡣࠊẼ⟶ࡀ௜╔ࡋࡓ≧ែ࡛⚄⤒࡞ᢡࠊᮏᏛ఍ࡢ๓㌟ࡢ⏕≀ࣜࢬ࣒◊✲఍ࡢᖺḟ኱఍࡛ࠊ⤌⧊ࢆษࡾฟࡋࠊẼ⟶ࡢ᩿㠃ࢆ㛤ཱྀࡋࡓ≧ែ࡛ᇵᆅᾮ⋊ ༠ ኱ Ꮫ ࡢ Ώ ㎶ ࿴ ே ඛ ⏕ ࠿ ࡽ ࠊ Mitsuhashi ࡜᫬㛫⏕≀Ꮫ㻌㼂㼛㼘㻚㻞㻣㻘㻌㻺㼛㻚㻌㻞㻌㻔㻞㻜㻞㻝㻕㻤㻡

Maramorsch ࡢᇵᆅ㸦MM ᇵᆅ㸧ࡀ౑࠼ࡿ࠿ࡶ▱ࢀ࡞ഃࡢど⚄⤒ࢆษ᩿ࡋ࡚┣┠࡟ࡋࠊṇᖖഃࡣ」║ࢆ㏻ࡌ࠸࡜ࠊᩍ࠼࡚࠸ࡓࡔ࠸ࡓࠋࡑࡇ࡛ࠊࡉࡗࡑࡃࡇࡢᇵᆅ࡚᫂ᬯ 13:13 ࢆ୚࠼ࡿࡇ࡜࡛ࠊ26 ᫬㛫࿘ᮇ࡛㥑ືࡋࢆ౑ࡗ࡚ࡳࡓ࡜ࡇࢁࠊ㠀ᖖ࡟Ⰻዲ࡛ࠊ㸯㐌㛫⛬ᗘᇵ㣴ࡓࠋᕥྑࡢ᫬ィ㛫࡟┦஫స⏝ࡀ࡞࠸࡜᝿ᐃࡍࢀࡤࠊ┣ୗ࡛㟁Ẽάືࢆグ㘓ࡍࡿࡇ࡜ࡀ࡛ࡁࡿࡼ࠺࡟࡞ࡗࡓࠋ┠ഃࡣᜏᬯ᮲௳࡜ྠ➼ࡢ᮲௳࡟⨨࠿ࢀࡿࡢ࡛ࠊ24 ᫬ࡑࡢ⤖ᯝࠊどⴥࡢ⚄⤒άືࡣᇵ㣴ୗ࡛ࡶࠊ୺ほⓗኪ㧗㛫ࡼࡾࡸࡸ▷࠸࿘ᮇ࡛⮬⏤⥅⥆ࡍࡿࡣࡎ࡛࠶ࡿࠋᐇ㝿ࡃࠊ᫨ప࠸ࣜࢬ࣒ࢆ♧ࡍࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡾࠊどⴥ࡟࡟ࡣࠊṇᖖഃࡣ᫂ᬯ࿘ᮇ࡟ྠㄪࡋ࡚ṇ☜࡟ 26 ᫬㛫ࡢ᫬ィࡀᅾࡿࡇ࡜ࢆᐇドࡍࡿࡇ࡜ࡀ࡛ࡁࡓ㸦ᅗ 4㸧9ࠋ࿘ᮇ࡛άືࣜࢬ࣒ࢆ㥑ືࡋࡓࡀࠊ┣┠ഃࡢ㥑ືࡍࡿࣜࢬ࣒ࡣṇᖖഃࡢάືࣜࢬ࣒࡜ࡢ఩┦㛵ಀ࡟౫Ꮡࡋࡓᕥྑどⴥ᫬ィࡢྠㄪᶵᵓ

࿘ᮇࡢኚㄪࢆ♧ࡋࡓ㸦ᅗ 5A㸧10ࠊ11ࠋ┣┠ഃࡢ࿘ᮇࡣࠊࡉ࡚ࠊどⴥࡣᕥྑ࡟୍ᑐ࠶ࡿࡀࠊṌ⾜άື࡟ࡣ㏻ᖖṇᖖഃࡢάືࡀ┣┠ഃࡢ୺ほⓗ᫨࡟࠶ࢀࡤ▷⦰ࡋࠊ୺୍ࡘࡢࣜࢬ࣒ࡋ࠿⌧ࢀ࡞࠸ࠋࡇࢀࡣᕥྑࡢ᫬ィࡀྠㄪほⓗኪ࡟࠶ࢀࡤᘏ㛗ࡍࡿ㸦ᅗ 5B㸧
ࠋࡇࢀࡽࡢ⤖ᯝ࠿ࡽࠊࡋ࡚ືࡃࡓࡵ࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋࡑࡇ࡛ࠊࡇࡢ⫼ᚋṇᖖಶయ࡛ࡣ┦஫࡟఩┦ࢆ୍⮴ࡉࡏࡿࡼ࠺࡞┦஫స࡟࠶ࡿ┦஫ྠㄪᶵᵓࢆゎᯒࡍࡿࡇ࡜࡟ࡋࡓࠋ㏻ᖖࡣྠ

⏝ࡀാ࠸࡚࠸ࡿࡇ࡜ࡀ♧၀ࡉࢀࡓ㸦ᅗ 5C㸧
ࠋࡉࡽ࡟ࠊㄪࡋ࡚ືࡃᕥྑࡢ᫬ィࢆ⬺ྠㄪࡉࡏࡿࡓࡵ࡟ࠊᕥྑࡢάື㔞ࡣࠊάື㛤ጞࡀ཯ᑐഃࡢ୺ほⓗኪ࡟࠶ࢀࡤቑຍ

᫬ィࢆ␗࡞ࡿ࿘ᮇ࡛ື࠿ࡍࡇ࡜ࢆヨࡳࡓࠋࡍ࡞ࢃࡕ∦ࡋࠊ୺ほⓗ᫨࡟࠶ࢀࡤῶᑡࡋࡓ㸦ᅗ 5A㸧10,11ࠋᚑࡗ࡚ࠊᅗ  ࣇࢱ࣍ࢩࢥ࢜ࣟࢠ࡟࠾ࡅࡿᕥྑどⴥᴫ᪥᫬ィ㛫ࡢ┦஫స⏝ࠋ㸦$㸧‫ࡓࡋ♧࡛ڹ‬᪥࡟∦ഃど⚄⤒ࢆษ᩿ࡋࠊṇᖖഃࡢ」║࡟᫂ᬯ ࢆ୚࠼ࡓሙྜࡢάືグ㘓ࠋᗘࡣ Υࠋࢢ࣮ࣞࡢᙳࢆࡘࡅࡓ㒊ศࡀᬯᮇࢆ♧ࡋ࡚࠸ࡿࠋ᫂ᬯ࿘ᮇ࡟ྠㄪࡋ࡚  ᫬㛫ࡢ࿘ᮇࢆ♧ࡍᡂศ㸦ṇᖖഃ㸧࡜ࠊ⮬⏤⥅⥆ࡍࡿᡂศ㸦┣┠ഃ㸧ࡀྠ᫬࡟⌧ࢀ࡚࠸ࡿࡀࠊ⮬⏤⥅⥆ᡂศࡢ࿘ᮇࡣྠㄪᡂศ࡜ࡢ఩┦㛵ಀ࡟ᛂࡌ࡚ኚ ໬ ࡋ ࡚ ࠸ ࡿ ࠋ <XNL]DQH 7RPLRND ࢆᨵኚࠋ㸦%㸧⮬⏤⥅⥆ᡂศࡢ࿘ᮇࡢኚㄪࠋᶓ㍈ࡣ⮬⏤⥅⥆ᡂศࡢᴫ᪥᫬้ࢆࠊ⦪㍈ࡣ⮬⏤⥅⥆ᡂศࡢ࿘ᮇࡢᖹᆒ࠿ࡽࡢ೫ᕪࢆ♧ࡋ࡚࠸ࡿࠋྛⅬࡣྠㄪᡂศࡢάືࡀ㛤ጞࡍࡿ⮬⏤⥅⥆ᡂศࡢᴫ᪥᫬้࡜ࡑࡢ᫬⏕ࡎࡿ⮬⏤⥅⥆ᡂศࡢ࿘ᮇࡢᖹᆒ࠿ࡽࡢኚ໬ࢆ♧ࡍࠋ⮬⏤⥅⥆ᡂศࡢ࿘ᮇࡣࠊྠㄪᡂศࡀ⮬⏤⥅⥆ᡂศࡢ୺ほⓗኪ࡟࠶ࡿሙྜ
࡟ࡣᘏ㛗ࡋࠊ୺ほⓗ᫨࡟࠶ࡿሙྜ࡟ ࡣ ▷ ⦰ ࡍ ࡿ ࠋ <XNL]DQH
7RPLRND ࢆᨵኚࠋ㸦&㸧ᕥྑࡢ┦஫స⏝ࡢᶍᘧᅗࠋᕥྑࡢどⴥ᫬ィࡣࡑࢀࡒࢀྠഃࡢ」║࠿ࡽධຊࡉࢀࡿග࿘ᮇ࡟ྠㄪࡍࡿࡀࠊᕥྑࡢ᫬ィࡣ┦஫࡟ྠㄪࡍࡿ௙⤌ࡳࢆഛ࠼࡚࠸ࡿࠋ
㸦'㸧ᕥྑどⴥ᫬ィ㛫ࡢ┦஫స⏝࡟㛵ಀࡋࡓ⚄⤒㊰ࠋᕥࡢど᯶ࢆษ᩿ࡋࠊࡑࡇ࠿ࡽ 1L&O ࢆࣂࢵࢡࣇ࢕ࣝࡍࡿࡇ࡜࡛ᰁⰍࡉࢀࡓ⚄⤒㊰ࢆࢫࢣࢵࢳࡋࡓࠋ▮༳ࡣᕥྑࡢど㧊㒊ศࢆ┤᥋㐃⤖ࡍࡿࢽ࣮ࣗࣟࣥ⩌ࡢ㍈⣴࡛ࠊࡇࡢ㍈⣴㊰ࢆษ᩿ࡍࡿ࡜ࠊ࿘ᮇࡢኚㄪࡣᾘኻࡍ
ࡿࠋ7RPLRNDHWDO ࢆᨵኚࠋ᫬㛫⏕≀Ꮫ㻌㼂㼛㼘㻚㻞㻣㻘㻌㻺㼛㻚㻌㻞㻌㻔㻞㻜㻞㻝㻕㻤㻢ࡇࡢ࣮࣌ࢪ࣮࢝ࣛ༳ๅ᪩㏿ࠊᢞ୚ࡋ࡚ࡳࡓ࡜ࡇࢁࠊࢥ࢜ࣟࢠࡢάືࣜࢬ࣒ࡀ᏶඲࡟ᾘኻࡍࡿࡇ࡜ࡀศ࠿ࡗࡓ 16ࠋࡇࢀࢆዎᶵ࡜ࡋ࡚ࠊᵝࠎ࡞᫬ィ㑇ఏᏊࢆࢡ࣮ࣟࢽࣥࢢࡋࠊࡑࡢ 2 ᮏ㙐RNA ࡢຠᯝࢆぢࡿ࡜࠸࠺㏫㑇ఏᏛⓗᡭἲ࡛ࠊ᫬ィࡢ᣺ືᶵᵓࠊගྠㄪᶵᵓࠊග࿘᫬ᶵᵓ࡞࡝ࡢゎᯒࢆ㐍ࡵࡿࡇ࡜ࡀ࡛ࡁࡓࠋ◊✲㈝ࡢ㠃࡛ࡣࠊእ㒊㈨㔠࡟ຍ࠼࡚ᒸᒣ኱Ꮫ㔜Ⅼ◊✲ࡢᨭ᥼ࡀ㡬ࡅࡓࡇ࡜ࡀ㠀ᖖ࡟᭷㞴࠸ࡇ࡜࡛࠶ࡗࡓࠋࡇࡢ࠾㝜࡛๭ྜ᪩ᮇ࡟ real-timePCR ⿦⨨ࢆᑟධࡍࡿࡇ࡜ࡀ࡛ࡁࠊศᏊ⏕≀Ꮫⓗ࡞◊✲ࢆᒎ㛤ࡍࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡇࡢࡼ࠺࡟ࠊᒸᒣ኱Ꮫ࡛ࡣ⚄⤒⾜ືᏛ࠿ࡽศᏊ⏕≀Ꮫ࡬࡜኱ࡁࡃ᪉ྥ㌿᥮ࡋࠊ᪻⹸࡟౛࠼ࢀࡤኚែࢆ⤒㦂ࡋࡓࡼ࠺࡟ᛮ࠺ࠋM2 ࡢ⤊ࢃࡾࡇࢁࠊ࠶ࡿඛ⏕࠿ࡽࠕ࡝࠺ࡋ࡚⬻ࢆࡍࡾࡘࡪࡉ࡞࠸ࡢ㸽ࠖ࡜ศᏊ⏕≀Ꮫⓗᡭἲࡢᑟධࢆ㐍ࡵ࡚㡬࠸ࡓᢡࠊᅗ  ࢥ࢜ࣟࢠᴫ᪥᫬ィศᏊ᣺ືᶵᵓࡢ௬ㄝࠋ᫬ィᶵᵓ࡟ࡣ per/tim ࣮ࣝࣉ࡟ຍ࠼࡚ࠊcry2 ࡢ᣺ື࣮ࣝࣉࡀ࠶ࡿࠋ࠸ࡎࢀࡶ㌿෗ࡢάᛶ໬ࡣ &/.&<& ࡟ࡼࡾࠊ⏘≀ࢱࣥࣃࢡ㉁ࡢ㈇ࡢࣇ࢕࣮ࢻࣂࢵࢡ࡟ࡼࡾⓎ᣺ࡍࡿࠋࡇࡢ௚࡟ࠊ&<& ࡶ࿘ᮇⓗ࡟Ⓨ⌧ࡍࡿࡀࠊࡇࢀ࡟ࡣ࠾ࡑࡽࡃ E75 ࡜ HR3 ࡀ㛵୚ࡋ࡚࠸ࡿࠋࡲࡓࠊ&/. ࡶ᮲௳࡟ࡼࡗ࡚࿘ᮇⓗ࡟Ⓨ⌧ࡍࡿࡀࠊࡑࡇ࡟
ࡣ vri ࡜ Pdp1 ࡀ㛵୚ࡍࡿྍ⬟ᛶࡀ㧗࠸ࠋࡇࢀࡽ࡟ຍ࠼࡚ࠊcwoࡶ᣺ືᶵᵓ࡟㛵୚ࡍࡿྍ⬟ᛶࡀ♧၀ࡉࢀ࡚࠸ࡿࠋ7RNXRND HWDO ࢆᨵኚࠋࠕඛ⏕ࠊࡍࡾࡘࡪࡋ࡚ඖࡢᙧࢆኻࡃࡋࡓࡽࠊఱࡶศ࠿ࡾࡲࡏࢇࡼࠋࠖ࡞࡝࡜ゝࡗ࡚࠸ࡓࡇ࡜ࢆ᝿࠸ฟࡋࠊᑡࠎࡁࡲࡾࡀᝏ࠸ᛮ࠸ࢆࡋ࡚࠸ࡿࠋࡇࢀࡲ࡛࡟᫂ࡽ࠿࡟࡞ࡗࡓࢥ࢜ࣟࢠᴫ᪥᫬ィࡢศᏊ᣺ືᶵᵓࡣࠊper/tim ࡢ㈇ࡢ㌿෗̺⩻ヂࣇ࢕࣮ࢻࣂ
ࢵࢡ࣮ࣝࣉ࡜ cry2 ࡢࣇ࢕࣮ࢻࣂࢵࢡ࣮ࣝࣉࢆྵࢇ࡛࠸ࡿ㸦ᅗ 6㸧16-18ࠋ࠸ࡎࢀࡢ࣮ࣝࣉࡶ CLK/CYC ࡀ㌿෗άᛶ໬ᅉᏊ࡜ࡋ࡚ാࡁࠊper/tim ࠾ࡼࡧ cry2 ࡢ㌿ᕥྑࡢ᫬ィࡣࠊ┦஫࡟୺ほⓗ᫨࡟ࡣ┦ᡭ᪉ࡢ㥑ືࡍࡿ෗ࢆάᛶ໬ࡍࡿࠋper/tim ࣮ࣝࣉ࡛ࡣࠊド᫂ࡣ࡛ࡁ࡚άືࢆᢚไࡋࠊኪ࡟ࡣቑᙉࡍࡿࡇ࡜ࡶ᫂ࡽ࠿࡜࡞ࡗࡓࠋ࠸࡞࠸ࡀࠊRNAi ࡢ≧ἣドᣐ࠿ࡽࠊ⏘≀ࢱࣥࣃࢡࡇࡢ┦஫ྠㄪ࡜ࠊάື㔞ࡢไᚚ࡟ࡼࡾࠊṇᖖಶయ࡛ࡣ

PER/TIM ࡀ」ྜయࢆᙧᡂࡋ࡚ CLK/CYC ࡢ㌿෗άᛶ୍㈏ࡋࡓኪ⾜ᛶࡢάືࣜࢬ࣒ࢆ⌧ࡍࡇ࡜ࡀ♧၀ࡉࢀࢆ ᢚ ไ ࡍ ࡿ ࡜ ⪃ ࠼ ࡚ ࠸ ࡿ ࠋ ୍ ᪉ ࠊ cry2 ࡣ ྠ ࡌ ࡃࡓࠋᘬࡁ⥆ࡃヲ⣽࡞ゎᯒ࠿ࡽࠊ┦஫స⏝࡟࠿࠿ࢃࡿ⚄CLK/CYC ࡟ࡼࡾ㌿෗ࡀάᛶ໬ࡉࢀࡿࡀࠊmRNA ࡟⤒㊰ࢆ≉ᐃࡋ㸦ᅗ 5D㸧ࠊࡉࡽ࡟ࢭࣟࢺࢽࣥࡀࡇࡢ┦஫

ࡣ 7 ✀ࡢࢫࣉࣛ࢖ࢩࣥࢢࣂࣜ࢔ࣥࢺࡀ࠶ࡾࠊࡑࡢ࠺ࡕ

స⏝࡟࠿࠿ࢃࡿࡇ࡜ࡶ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࡀ࡛ࡁࡓ 12-ᩘ✀ࡢ⏘≀ࢱࣥࣃࢡࡀࣂࣜ࢔ࣥࢺ㛫ࡲࡓࡣ CRY1 ࡜15ࠋ」ྜయࢆᙧᡂࡋ࡚ CLK/CYC ࡢάᛶࢆᢚไࡍࡿ 17ࠋ⯆࿡῝࠸ࡇ࡜࡟ࠊtim ࡢ RNAi ࡛ࡣάືࣜࢬ࣒ࡀ⥅⥆ࡋࢥ࢜ࣟࢠᴫ᪥᫬ィࡢศᏊ᣺ືᶵᵓ19ࠊࡑࡢሙྜ࡟ࡣ࡯࡜ࢇ࡝ࡢ᫬ィ㑇ఏᏊࡢⓎ⌧ࣜࢬ࣒2003 ᖺ࡟ᒸᒣ኱࡟㉱௵ࡋ࡚࠿ࡽࡣࠊศᏊ⏕≀Ꮫⓗࡀᾘኻࡍࡿࡀ cry2 ࡣⓎ⌧ࣜࢬ࣒ࢆ⥔ᣢࡍࡿࠋ୍᪉ࠊᡭἲࢆᑟධࡋࠊ᫬ィࡢ᣺ືᶵᵓࠊගྠㄪᶵᵓࠊࡉࡽ࡟cry1/cry2 ࡢ RNAi ࡛ࡶࡸࡣࡾάືࣜࢬ࣒ࡀ⥅⥆ࡋࠊࡣᏘ⠇㐺ᛂᶵᵓ࡞࡝ࡢ◊✲ࢆ㐍ࡵ࡚ࡁࡓࠋᑐ㇟ࡶࣇࢱ

ࡇࡢሙྜ࡟ࡣ tim ࡀ࿘ᮇⓗ࡟Ⓨ⌧ࡍࡿ 17ࠋࡇࢀࡽࡢ஦࣍ࢩࢥ࢜ࣟࢠ࠿ࡽࠊ࢟࢖ࣟࢩࣙ࢘ࢪࣙ࢘ࣂ࢚ࠊග࿘ᛶ

ᐇ࠿ࡽࠊper/tim ࣮ࣝࣉ࡜ cry2 ࣮ࣝࣉࡣ⊂❧࡟᣺ືࡢ᫂☜࡞ࢱࣥ࣎ࢥ࢜ࣟࢠ㸦Modicogryllus siamensis㸧ࠊࡍࡿ࡜⪃࠼࡚࠸ࡿࠋཎ ጞ ⓗ ࡞ ↓ ኚ ែ ᪻ ⹸ ࣐ ࢲ ࣛ ࢩ ࣑ 㸦 Thermobiaࢥ࢜ࣟࢠࡢ᣺ືᶵᵓ࡟ࡣࡇࢀࡽ࡟ຍ࠼࡚ࠊcyc ࡢ᪥domestica㸧࡟ࡲ࡛ᗈࡆ࡚ࡁࡓࠋᒣ࠶ࡾ㇂࠶ࡾ࡛࠶ࡗ

࿘Ⓨ⌧࡜ cwo ࡢ᪥࿘Ⓨ⌧ࡢ࣮ࣝࣉࡀ࠶ࡿࡇ࡜ࡀ♧၀ࡓࡀࠊ◊✲ࢆ㐍ࡵࡿࡇ࡜ࡀ࡛ࡁࡓࡢࡣ RNAi ࢆ᪩ᮇ࡟ࡉࢀ࡚࠸ࡿ 20ࠊ21ࠋࡉࡽ࡟ࠊcyc ࡢ RNAi ࡟ࡼࡾ Clk ࡀᑟධ࡛ࡁࡓⅬ࡟࠶ࡗࡓ࡜ᛮ࠺ࠋࡇࢀ࡟ࡣࠊᚨᓥ኱Ꮫᕤ᪥࿘Ⓨ⌧ࢆ♧ࡍࡇ࡜࠿ࡽࠊClk ࡶ₯ᅾⓗ࡟࿘ᮇⓎ⌧ࡍᏛ㒊ࡢ㔝ᆅ⃈ᬕඛ⏕㸦⌧ᚨᓥ኱Ꮫ㛗㸧࡟኱ኚ࠾ୡヰ࡟ࡿ௙⤌ࡳࢆഛ࠼࡚࠸ࡿࡽࡋ࠸ 21ࠋ࡞ࡗࡓࠋᒸᒣ኱࡟㉱௵ࡋ࡚㛫ࡶ࡞࠸ࡇࢁࠊ㔝ᆅඛ⏕࠿ࡽࠕࢥ࢜ࣟࢠ࡛ࡣⓎ⏕࡟㛵୚ࡍࡿ㑇ఏᏊࡢ RNAi ࡀ㠀どⴥእ᫬ィᖖ࡟ࡼࡃຠࡃࡢ࡛ࠊper ࡢ 2 ᮏ㙐 RNA ࡢࣜࢬ࣒࡬ࡢ

ୖ㏙ࡢࡼ࠺࡟ࢥ࢜ࣟࢠ࡛ࡣ LM 」ྜయࢆษ㝖ࡍࡿຠᯝࢆㄪ࡭࡚ࡳ࡚ࡣ࡝࠺࡛ࡍ࠿ࠖ࡜࠾ㄏ࠸ࢆ㡬࠸ࡓࠋ࡜Ṍ⾜άືࣜࢬ࣒ࡀᾘኻࡍࡿࡀࠊಶయ࡟ࡼࡗ࡚ࡣษ㝖᫬㛫⏕≀Ꮫ㻌㼂㼛㼘㻚㻞㻣㻘㻌㻺㼛㻚㻌㻞㻌㻔㻞㻜㻞㻝㻕㻤㻣ᚋᩘ᪥㛫ᙅ࠸ࣜࢬ࣒ࢆ⥔ᣢࡍࡿሙྜࡀ࠶ࡿ 22ࠋࡲࡓࠊLM 」ྜయࢆษ㝖ࡍࡿ࡜ࠊ๓⫶࡛ࡣ per ࡜ tim
ࢀࡓ 25ࠋ

LM 」ྜయࡢษ㝖ᚋど⚄⤒࡜ど᯶࡜ࡢ⚄⤒㐃⤡ࡀ෌ࡢ୧᪉ࡢࣜࢬ࣒ࡀኻࢃࢀࠊ୰⭠࡜᭱⤊⭡㒊⚄⤒⠇࡛ࡣ⏕ࡋࡓሙྜ࡟ࠊࡋࡤࡋࡤග࡟ྠㄪࡋࡓṌ⾜άືࣜࢬ࣒

tim ࡢⓎ⌧ࡀ୙つ๎࡟࡞ࡗࡓࡀࠊper ࡢⓎ⌧ࡣ⥔ᣢࡉࡀ⌧ࢀࠊࡑࢀࡀᜏᬯ᮲௳ୗ࡛ࡶࡋࡤࡽࡃ⥅⥆ࡍࡿ 23ࠋࢀࡓࠋ⬻࡛ࡣࠊper ࡜ tim ࡢ୧᪉ࡢ mRNA ࡢࣜࢬ࣒ᚑࡗ࡚ࠊどⴥእ࡟ᙅ࠸࡞ࡀࡽάືࣜࢬ࣒ࢆไᚚࡍࡿ᫬ࡀ⥔ᣢࡉࢀࡓࡀࠊṇᖖಶయ࡜ẚ㍑ࡋ࡚఩┦ࡢࡎࢀࡀほィࡀᅾࡿ࡜⪃࠼ࡽࢀࡿࠋRence ࡜ Loher24 ࡶู✀ࡢࢥᐹࡉࢀࡓࠋࡇࢀࡽࡢ⤖ᯝ࠿ࡽࠊ୰⭠ࠊ᭱⤊⭡㒊⚄⤒⠇ࠊ࢜ࣟࢠ Teleogryllus commodus ࡛ㄏᘬḷࡢⓎ㡢⾜ື⬻࡟ࡣᴫ᪥᫬ィࡀᅾࡾࠊࡇࢀࡽࡢどⴥእ᫬ィࡣどⴥ࠿ࣜࢬ࣒ࢆไᚚࡍࡿ᫬ィࡀどⴥእ࡟ࡶ࠶ࡿྍ⬟ᛶࢆ♧ࡽࡢไᚚࢆཷࡅ࡚࠸ࡿࡀࠊࡑࡢ⛬ᗘࡀ⤌⧊࡟ࡼࡾ␗࡞၀ࡋ࡚࠸ࡿࠋ㞝ࢥ࢜ࣟࢠࡣኪ㛫࡟άⓎ࡟Ⓨ㡢ࢆ⾜࠺᫂ࡿࡇ࡜ࡀ♧၀ࡉࢀࡓ 25ࠋࢩࣙ࢘ࢪࣙ࢘ࣂ࢚࡛ࡣࠊ࠿ࡽ░࡞ᴫ᪥ࣜࢬ࣒ࢆ♧ࡍࠋᙼࡽࡣࠊどⴥࢆษ㝖ࡉࢀࡓࢥࡔࡢ࡯࡜ࢇ࡝ࡢ⤌⧊࡟᫬ィࡀᅾࡾࠊࡑࢀࡽࡢከࡃࡣಶ࢜ࣟࢠ࡛ࠊᜏ᫂᮲௳ୗ࡛↓࿘ᮇ࡟࡞ࡗ࡚࠸ࡓⓎ㡢⾜ືู࡟ග࡟ྠㄪࡋ⊂❧ࡢࣜࢬ࣒ࢆ้ࡴ࡜⪃࠼ࡽࢀ࡚࠸

ࡀࠊ24 ᫬㛫ࡢ

ࡿ 26ࠊ27 ࡀࠊࢥ࢜ࣟࢠ࡛ࡣどⴥእ᫬ィࡢ୰ᯡ౫Ꮡᗘࡀᗘ࿘ᮇࢆ୚࠼ࡿ࡜ࣜࢬ࣒ࢆ♧ࡍࡼ࠺࡟࡞ࡾࠊࡇࡢࣜࢬ࣒ࡀᩘ᪥㛫ࡢ⛣⾜ᮇࢆకࡗ࡚ṇᖖಶࣁ࢚ࡼࡾࡶ㧗࠸ࡼ࠺࡛࠶ࡿࠋᮎᲈ᫬ィࡢ୰ᯡ౫Ꮡᗘࡣࠊయ࡜ྠᵝࡢ఩┦࡛άືᮇ࡟ගࢆཷࡅࡿ᫨⾜ᛶື≀࡛ࡣᮎᲈ᫬ィࡀಶูᗘ࿘ᮇ࡟ྠㄪࡍࡿࡇ࡜࡞࡝ࢆሗ࿌ࡋ࡚࠸ࡿࠋ࡟ග࡟ྠㄪࡍࡿࡓࡵపࡃࠊάືᮇ࡟ගࡀஈࡋ࠸ኪ⾜ᛶどⴥእ᫬ィ࡜どⴥ᫬ィ࡜ࡢ㛵ಀࢆ᥈ࡿࡓࡵࠊ⬻ࠊ᭱ື≀࡛ࡣ㧗࠸࡜ࡍࡿ⪃࠼ࡀ࠶ࡿ 28 ࡀࠊࢥ࢜ࣟࢠࡢሙྜ⤊⭡㒊⚄⤒⠇࡜๓⫶ࠊ୰⭠࡞࡝ࡢᮎᲈჾᐁ࡟ࡘ࠸࡚᫬࡟ࡣࡇࡢㄝࡣᙜ࡚ࡣࡲࡽ࡞࠸ࠋ๓㏙ࡢࡼ࠺࡟ࢥ࢜ࣟࢠィ㑇ఏᏊࡢⓎ⌧ࢆ᳨ウࡋࡓࠋࡑࡢ⤖ᯝࠊᜏᬯ᮲௳ୗ࡛ࡣᗂ⹸ᮇ࡟ࡣ᫨⾜ᛶࢆ♧ࡍࡀࠊᗂ⹸ᮇࡢどⴥእ᫬ィࡢperࠊ tim ࡀ࿘ᮇⓗ࡟Ⓨ⌧ࡍࡿࡇ࡜࠿ࡽࠊࡇࢀࡽࡢ⚄୰ᯡ౫Ꮡᛶࢆ᳨ウࡋࡓ࡜ࡇࢁࠊᡂ⹸ࡼࡾࡶࡴࡋࢁ୰ᯡ⤒⤌⧊ࡸᮎᲈჾᐁ࡟ࡶᴫ᪥ࣜࢬ࣒ࡀᅾࡿࡇ࡜ࡀ♧ࡉ౫Ꮡᗘࡀ㧗࠸࡜࠸࠺⤖ᯝࡀᚓࡽࢀ࡚࠸ࡿ 29ࠋᅗ  Ṍ⾜άືࣜࢬ࣒ࡢග࿘ᮇ࡬ࡢ෌ྠㄪ㐣⛬ࢆᑐ㇟࡜ࡋࡓࠊගྠㄪ࡟㛵୚ࡍࡿ㑇ఏᏊࡢ 51$L ࡟ࡼࡿᶵ⬟ゎᯒࠋ㸦$㸧ࢧࣥࢦ⏤᮶ࡢ㑇ఏᏊ DsRed2 ࡢ  ᮏ㙐ࢆᢞ୚ࡉࢀࡓࢥࣥࢺ࣮ࣟࣝಶయࡢ  ᫬㛫఩┦๓㐍㸦ୖ㸧࡜ᚋ㏥㸦ୗ㸧ᚋࡢ᫂ᬯ࿘
ᮇ࡬ࡢ෌ྠㄪࠋ࠸ࡎࢀࡶᩘࢧ࢖ࢡࣝࡢ⛣⾜ᮇࢆ⤒࡚෌ྠㄪࡋ࡚࠸ࡿࠋ㸦%㸧」║࡛Ⓨ⌧ࡍࡿ⥳ⰍගཷᐜศᏊ㑇ఏᏊ op-LW ࡢ 51$L ฎ⌮ಶయࡢάືࣜࢬ࣒ࠋࢃࡎ࠿࡞ UHODWLYHFRRUGLQDWLRQ ࡀࡳࡽࢀࡿ
ࡀࠊග࿘ᮇ࡟ࡣྠㄪ࡛ࡁ࡞࠸ࠋ.RPDGDHWDO ࢆᨵኚࠋ
㸦&㸧cry1 ࡜ cry2 ࡢ  㔜 51$L ฎ⌮ಶయࡢάືࣜࢬ࣒ࠋ఩┦๓㐍ࠊᚋ㏥࡜ࡶ෌ྠㄪࡀ␗ᖖ࡜࡞ࡿࠋ.XWDUDJLHWDO ࡼࡾࠋ
㸦'㸧tim51$L ฎ⌮ಶయࡢάືࣜࢬ࣒ࠋග࿘ᮇࡢ఩┦๓㐍᫬࡟ࡣྠㄪࡍࡿࡀ ୖ㸧ࠊ఩┦ᚋ㏥᫬࡟ࡣᛂ⟅࡛ࡁ࡞࠸㸦ୗ㸧ࠋ࢔ࢡࢺࢢ࣒ࣛୖ㒊ࡢⓑ㯮ࡢࣂ࣮ࡣ᫂㸦ⓑ㸧ᬯ㸦㯮㸧࿘ᮇࢆ♧ࡍࠋ࢔ࢡࢺࢢ࣒ࣛᕥࡢ㯮୕ゅࡣ᫂ᬯ࿘ᮇࢆ఩┦ኚ఩ࡉࡏࡓ᪥ࢆ♧ࡍࠋ᫬㛫⏕≀Ꮫ㻌㼂㼛㼘㻚㻞㻣㻘㻌㻺㼛㻚㻌㻞㻌㻔㻞㻜㻞㻝㻕㻤㻤ࡇࡢ࣮࣌ࢪ࣮࢝ࣛ༳ๅࢥ࢜ࣟࢠᴫ᪥᫬ィࡢගྠㄪᶵᵓ  ගཷᐜჾ⎔ቃࢧ࢖ࢡࣝ࡬ࡢྠㄪࡣࠊᴫ᪥᫬ィࡀάືࢆጞࡵ࡜㡿ᇦࡀ኱ࡁࡃ࡞ࡿ࡜఩┦ኚ఩ᚋࡢ᫂ᬯࢧ࢖ࢡࣝ࡬ࡢ
෌ྠㄪ࡟ᚲせ࡞᪥ᩘࡀቑຍࡍࡿࡀࠊྠㄪࡑࡢࡶࡢࡣጉ
ࡆࡽࢀ࡞࠸ 33ࠊ࡜࠸࠺⤖ᯝ࡜ྜ⮴ࡍࡿࠋࡍࡿᵝࠎ࡞⏕⌮ᶵ⬟ࡢ఩┦ࢆタᐃࡍࡿࡓࡵࡢ㔜せ࡞ᶵ⬟࡛࠶ࡿࠋ᫬ィࢆྠㄪࡉࡏࡿ⎔ቃᅉᏊࡣࠊගࠊ ᗘ  ගྠㄪࡢศᏊᶵᵓ

࡞࡝ࡀ࠶ࡿࡀࠊගࡀ᭱ࡶ㔜せ࡞ᅉᏊ࡛࠶ࡿࠋ᪻⹸ࡢග」║࠿ࡽࡢග᝟ሗࡣࠊど⚄⤒ࢆ⤒࡚᫬ィ㒊఩࡛࠶ࡿྠㄪᶵᵓࡣ࢟࢖ࣟࢩࣙ࢘ࢪࣙ࢘ࣂ࢚࡛᭱ࡶヲࡋࡃゎどⴥ࡟ఏ㐩ࡉࢀࡿࠋࢃࢀࢃࢀࡣࡇࢀࡲ࡛࡟ࠊどⴥ᫬ィᯒࡉࢀ࡚࠸ࡿࠋࣁ࢚࡛ࡣ⬻ෆࡢ᫬ィ⣽⬊ࡢ࠸ࡃࡘ࠿࡛⣽⬊࡛ࡢගྠㄪᶵᵓࡀ 2 ࡘࡢ⤒㊰࠿ࡽ࡞ࡿࡇ࡜ࢆ᫂

Ⓨ⌧ࡍࡿ CRY ࡀගཷᐜศᏊ࡜ࡋ࡚ᶵ⬟ࡋ࡚࠸ࡿ 30ࠋࡽ࠿࡟ࡋࡓ㸦ᅗ 8㸧ࠋ୍ࡘࡣ Pdp1 ࡢ㛵ࢃࡿ⤒㊰㸦Pdp1

CRY ࡣග౫Ꮡⓗ࡟ TIM ࡟స⏝ࡋศゎ࡟ᑟࡃࠋࡇࢀ࡟

⣔㸧࡛࠶ࡾ 34ࠊࡶ࠺୍ࡘࡣ cry1ࠊcry2 ࡢ㛵ࢃࡿ⣔㊰ࡼࡗ࡚ኪࡢ๓༙࡛ࡣ఩┦ᚋ㏥ࡀࠊኪࡢᚋ༙࡛ࡣ఩┦๓

㸦cry2 ⣔㸧࡛࠶ࡿ 35ࠋPdp1 ⣔ࡣ᫂ᮇࡀᘏ㛗ࡋࡓሙྜ㐍ࡀចࡁ㉳ࡇࡉࢀࠊගྠㄪ࡟ᑟ࠿ࢀࡿ 31ࠋࢥ࢜ࣟࢠ࡛

࡟ࡢࡳാࡃࠋ᫂ᮇࢆ 3 ᫬㛫ᘏ㛗ࡋࡓࡢࡕᜏᬯ࡟⨨࠸ࡓࡣ」║⥙⭷࠿ࡽどⴥ࡟ఙࡧࡿど⚄⤒ࢆษ᩿ࡍࡿ࡜άሙྜࠊάືࣜࢬ࣒ࡣ఩┦ᚋ㏥ࡍࡿࠋࡇࡢᚋ㏥㔞ࡣࠊ୍ືࣜࢬ࣒ࡀ᫂ᬯ࿘ᮇୗ࡛ࡶᜏᬯ᮲௳ୗࡢࡼ࠺࡟⮬⏤ᗘᬯ㯮࡟⨨࠸ࡓࡢࡕ୺ほⓗኪࡢึࡵ㸦CT12-15㸧࡟ 3⥅⥆ࢆጞࡵࡿࠋࢥ࢜ࣟࢠ࡟ࡣ 3 ಶࡢ༢║ࡀ࠶ࡿ㸦ᅗ 1)᫬㛫ࡢග↷ᑕࢆ⾜࡞ࡗࡓሙྜࡼࡾࠊࢃࡎ࠿࡟࡛ࡣ࠶ࡿࡀࠊࡇࢀࡽࡣ↓യ࡛ṧࡉࢀ࡚࠸࡚ࡶࠊྠㄪࡣ࡛ࡁ࡞࠸

ࡀ᭷ព࡟኱ࡁ࠸ 34ࠋ᫂ᮇࢆ 3 ᫬㛫ᘏ㛗ࡋࡓ᫬ࡢ᫬ィ㑇3ࠋᚑࡗ࡚ࠊ」║ࡀ၏୍ࡢගྠㄪࡢࡓࡵࡢගཷᐜჾ࡛࠶

ఏᏊࡢ mRNA ࢆ qPCR ࡛ࡿࠋࢥ࢜ࣟࢠ」║ෆ࡟ࡣ⣸እගࠊ㟷Ⰽගࠊ⥳Ⰽගࢆࡑ᫬㛫࡛ Pdp1 ࡢⓎ⌧㔞ࡀቑຍࡋࠊࡑࢀ࡟⥆࠸࡚ࠊClkࠊ

ࢀࡒࢀཷᐜࡍࡿࠊopsin-UVࠊopsin-Blueࠊopsin-LW

perࠊtim ࡢⓎ⌧㔞ࡀቑຍࡍࡿࡇ࡜ࡀศ࠿ࡗࡓࠋࡍ࡞

ࡢ 3 ✀ࡢගཷᐜศᏊࡀⓎ⌧ࡋ࡚࠸ࡿ 32ࠋࡇࢀࡽࡣ」║ࢃࡕࠊperࠊtim ࡢቑຍ࡟ࡼࡾ୺ほⓗኪࡀ㐜ᘏࡋ࡚ࣜෆ࡛≉ᚩⓗ࡞Ⓨ⌧ࣃࢱ࣮ࣥࢆ♧ࡋࠊopsin-UV ࡣ⭡ഃࢬ࣒ࡢ఩┦ᚋ㏥ࡀ⏕ࡎࡿ࡜⪃࠼ࡽࢀࡓࠋ࡜ࡇࢁࡀࠊ

㒊ࡢ୍㒊ࢆ㝖ࡁ඲ᇦ࡛ࠊಶ║࠶ࡓࡾ࠾ࡑࡽࡃ 1 ಶࡢど

CT12-15 ࡟ ග ↷ ᑕ ࢆ ⾜ ࡞ ࡗ ࡓ ሙ ྜ ࡸ ࠊ ኪ ࡢ ᚋ ༙⣽⬊࡛Ⓨ⌧ࡋ࡚࠾ࡾࠊopsin-Blue ࡣ⫼⦕㒊ࡢ኱㒊ศ

㸦ZT20-23㸧࡟ග↷ᑕࢆ⾜࡞ࡗࡓሙྜ࡟ࡣࠊ᫬ィ㑇ఏࡢど⣽⬊࡜⭡ഃ㒊࡛ opsin-UV ࡜⨨ࡁ᥮ࢃࡗ࡚Ⓨ⌧ࡋᏊࡢⓎ⌧㔞࡟ኚ໬ࡣぢࡽࢀ࡞࠿ࡗࡓ 34ࠋ୍ᗘᬯᮇࢆᣳ࡚࠸ࡿࠋOpsin-LW ࡣ⫼⦕㒊ࢆ㝖ࡃ㡿ᇦ࡛ opsin-UVࠊࡴ࡜ࠊPdp1 ⣔ࡣගㄏᑟࡀ࠿࠿ࡽ࡞࠸ࡼ࠺࡛࠶ࡿࠋ

ᐃࡋࡓ࡜ࡇࢁࠊ↷ᑕᚋ 1opsin-Blue Ⓨ⌧⣽⬊ࢆ㝖ࡃ⣽⬊࡛Ⓨ⌧ࡍࡿࠋ3 ✀ࡢගࡇࡇ࡛ࠊᬯ㯮ୗ࡛ࡢග↷ᑕ࡟ࡼࡿࠊ୺ほⓗኪ๓༙ࡢཷᐜศᏊࡢᶵ⬟ࢆ RNAi ࡟ࡼࡾゎᯒࡋࡓ࡜ࡇࢁࠊ఩┦ᚋ㏥ࡸ୺ほⓗኪᚋ༙ࡢ఩┦๓㐍ࡣ࡝ࡢࡼ࠺࡞௙

opsin-UV ࡜ opsin-Blue ࡢ RNAi ࡣගྠㄪ࡟࡯࡜ࢇ⤌ࡳ࡛⏕ࡎࡿࡢ࠿ࡀၥ㢟࡜࡞ࡿࠋࡇࢀࡲ࡛ࡢ⤖ᯝ࠿ࡽࠊ࡝ᙳ㡪ࡋ࡞࠸ࡀࠊopsin-LW ࡢⓎ⌧ᢚไ࡛άືࣜࢬ࣒

ࡇࡢ⣔࡟ࡣ cry1ࠊcry2 ࡀ㛵୚ࡍࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞

ࡢගྠㄪࡀᙉࡃ㜼ᐖࡉࢀࡿࡇ࡜ࡀศ࠿ࡗࡓ㸦ᅗ 7B㸧

ࡗࡓ 35ࠋcry1ࠊcry2 ࡢ༢⊂ࡢ RNAi ࡛ࡣගྠㄪࡣ඲32ࠋࡇࡢ⤖ᯝࡣࠊ」║ࡢ㒊ศษ㝖ࢆ⾜ࡗࡓሙྜࠊษ㝖ࡃ㜼ᐖࡉࢀ࡞࠸ࡀࠊcry1/cry2 ࡢ 2 㔜 RNAi ࡛ࡣࠊከᅗ  ࢥ࢜ࣟࢠᴫ᪥᫬ィࡢගྠㄪࡢศᏊᶵᵓࠋ
᫂ᮇࢆᘏ㛗ࡋࡓሙྜࡢ఩┦ᚋ㏥᫬࡟ࡣࠊPdp1 ࡀⓎ⌧ࡋࠊࡑࢀ࡟ࡼࡗ࡚ Clk ࡢⓎ⌧ࡀஹ㐍ࡋࠊࡉࡽ࡟ tim ࡀⓎ⌧ஹ㐍ࡍࡿࠋࡑࢀ࡟ࡼࡗ࡚୺ほⓗኪࡀ㐜ᘏࡋࠊ఩┦ᚋ㏥ࡀ⏕ࡎࡿࠋ୍ᗘᬯᮇࢆᣳࢇࡔሙྜ࡟ࡣࠊ୺ほⓗኪᚋ༙ࠊኪࡢ๓༙
ࡢ࠸ࡎࢀ࡛ࡶ c-fos ࡢⓎ⌧ࡀ⏕ࡌࠊࡑࡢᚋ &5<&5< ࡀ㛵ࢃࡿ⣔࡟ࡼࡗ࡚఩┦๓㐍ࠊ
ᚋ㏥ࡀ⏕ࡎࡿࠋࡇࢀࡲ࡛ࡢ࡜
ࡇࢁࠊ&5< ࡢୖὶ࡟ Brwd3
ࡸ Fbxl ࡀ㛵୚ࡍࡿྍ⬟ᛶࢆ♧ࡍ⤖ᯝࡀᚓࡽࢀ࡚࠸ࡿࠋࡲࡓࠊ୺ほⓗኪ๓༙ࡢග࡟ࡼࡿ఩┦ᚋ㏥࡟ࡣ tim ࡀᚲせ࡛࠶
ࡿࠋ.XWDUDJLHWDO ࢆᨵኚࠋ᫬㛫⏕≀Ꮫ㻌㼂㼛㼘㻚㻞㻣㻘㻌㻺㼛㻚㻌㻞㻌㻔㻞㻜㻞㻝㻕㻤㻥ࡃࡢಶయ࡛఩┦ኚ఩ᚋࡢ᫂ᬯ࿘ᮇ࡬ࡢ෌ྠㄪࡀ㜼ᐖ▷࠸ࠊ࠶ࡿ࠸ࡣ㛗࠸ಶయࢆసᡂࡋࠊࡑࡢ㛫࡛஺᥮⛣᳜ࡉࢀࡿ㸦ᅗ 7C㸧
ࠋ2 㔜 RNAi ฎ⌮ಶయ࡛ࡣࠊCT12-15

ࢆ⾜ࡗ࡚ࠊ⛣᳜ᚋࡣ donor ࡢ࿘ᮇࡀⓎ⌧ࡍࡿࡇ࡜ࢆ

࡛ࡢග↷ᑕࠊ࠾ࡼࡧ ZT20-23 ࡛ࡢග↷ᑕ࡟ࡼࡿ఩┦♧ࡋࡓ 37ࠋࡉࡽ࡟∦ഃࡢࡳ⛣᳜ࡍࡿ࡜ࠊṇᖖഃ࠿ࡽࡢ

ኚ఩ࡀᙉࡃ㜼ᐖࡉࢀࡿࡇ࡜ࡶศ࠿ࡗࡓࠋcry1ࠊcry2 ࡢᙉ࠸ᢚไ࡟ࡼࡾ⛣᳜ഃ࡟㥑ືࡉࢀࡿάືࡀ⌧ࢀ࡞࠸mRNA ࣞ࣋ࣝࡣࡇࢀࡽࡢග↷ᑕ᫬࡟ࡣኚ໬ࡋ࡞࠸ࡀࠊ

ࡀࠊṇᖖഃࡢど⚄⤒ᖿࢆษ᩿ࡍࡿࡇ࡜࡛⛣᳜ഃ࡟㥑ື

CRY2 ࢱࣥࣃࢡ㉁ࡣኪ㛫ࡢග↷ᑕ࡟ࡼࡾῶᑡࡍࡿࠋᚑ

ࡉࢀࡿάືࣜࢬ࣒ࡀ⌧ࢀࡿࡼ࠺࡟࡞ࡿࡇ࡜࡞࡝ࢆぢࡗ࡚ࠊ」║࠿ࡽࡢග᝟ሗࡀ CRY2 ࢱࣥࣃࢡࡢኚ໬ࢆ

ฟࡋ࡚࠸ࡿ 37ࠋࡇࢀࡽࡢ⤖ᯝࡣࠊどⴥࡀ᫬ィࡢᗙ࡛࠶ㄏᑟࡍࡿࡇ࡜࡜࡞ࡿࡀࠊࢃࢀࢃࢀࡣࡇࡢ⣔࡟ c-fos ࡀࡿⅬࠊどⴥ㛫࡟┦஫άືᢚไᶵᵓࡀ࠶ࡿⅬ࡞࡝ࡀࠊࢥ㛵୚ࡍࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡋ࡚࠸ࡿ㸦ᅗ 8㸧35ࠋCT12-15

࢜ࣟࢠ࡜ࢦ࢟ࣈࣜ࡜࡟ඹ㏻ࡍࡿࡇ࡜ࢆ♧ࡋ࡚࠸ࡿࠋ୍

࠶ࡿ࠸ࡣ ZT20-23 ࡛ࡢග↷ᑕ࡟ࡼࡾࠊc-fos Ⓨ⌧㔞ࡣ᪉ࠊࢦ࢟ࣈ࡛ࣜࡣどᑠⴥࡢ⭡ഃ࡞࠸ࡋࡣど㧊⭡ഃ๓᪉᭷ព࡟ୖ᪼ࡍࡿࠋcry1ࠊcry2 ࡢ RNAi ࡣ c-fos ࡢගㄏ㒊࡟࠶ࡿ๪ど㧊࡟᫬ィࡀᅾࡿࡇ࡜ࡀ᝿ᐃࡉࢀ࡚࠸ࡿᑟ࡟ᙳ㡪ࡋ࡞࠸ࡇ࡜ࠊc-fos ࡢ RNAi ࡛ࡣ఩┦ኚ఩ࡀࡀ 38ࠊ39ࠊࢥ࢜ࣟࢠ࡛ࡣどⴥᯈ࡜ど㧊ࡢ㛫࡟࠶ࡿእ࢟࢔

ᙉࡃᢚไࡉࢀࡿࡇ࡜ࠊࡉࡽ࡟ opsin-LW ࡢ RNAi ࡛ c-ࢬ࣐௜㏆࡟᫬ィ⣽⬊ࡀ࠶ࡿࡇ࡜ࡀ♧၀ࡉࢀ࡚࠾ࡾࠊ⣽fos ࡢගㄏᑟࡀᢚไࡉࢀࡿࡇ࡜࠿ࡽࠊ᫬ィ⣽⬊࡛ࡣ࠿࠸Ⅼ࡛ࡣ㐪࠸ࡀ࠶ࡿࠋ

opsin-LW Ⓨ⌧⣽⬊࠿ࡽࡢ᝟ሗࡀ c-fos ࢆㄏᑟࡋࠊࡑࣁ࢚࡛ࡣࠊ⬻ࡢഃ᪉どⴥᐤࡾࡢ㒊ศ࡜⬻⫼ഃ㒊࡟᫬ࢀࡀఱࡽ࠿ࡢ⤒㊰ࢆ⤒࡚ CRY2 ࡢศゎࢆㄏᑟࡍࡿ࡜

ィ⣽⬊ࡀ࠶ࡿࡇ࡜ࡀ♧ࡉࢀ࡚࠸ࡿ 40ࠋࡇࢀࡽࡢ࠺ࡕ≉⪃࠼ࡽࢀࡿࠋIn situ hybridization ࡜ in situ PCR ࡟࡟ࠊ⬻ഃ᪉㒊ࡢᑠᆺࡢ⣽⬊㸦sLNv㸧ࡀάືࣜࢬ࣒ࡢ

ࡼࡾࠊperࠊ cry2 ࢆⓎ⌧ࡍࡿ᫬ィೃ⿵⣽⬊࡛ c-fos ࡶไᚚ࡟㛵୚ࡍࡿࡇ࡜ࡀ♧၀ࡉࢀ࡚࠸ࡿ 41ࠋ᫬ィ⣽⬊ࡢc-fos ࡀ఩⨨ࡣࡎ࠸ࡪࢇࢥ࢜ࣟࢠ࡜ࡣ␗࡞ࡗ࡚࠸ࡿࡀࠊ⬻ࡢᵓ

CRY2 ࡢගศゎࢆㄏᑟࡍࡿ⣔ࡢゎᯒࢆ㐍ࡵ࡚࠸ࡿࠋࡇ㐀ࡀ୧⪅࡛␗࡞ࡗ࡚࠾ࡾࠊⓎ⏕㐣⛬ࢆ㏣ࡗ࡚ࡑࡢ㉳※ࢀࡲ࡛ࡢ࡜ࡇࢁࠊࡇࡢ⣔࡟ࡣ Brwd3ࠊFbxl ࡞࡝ࡀ㛵ࢆࡓ࡝ࢀࡤࠊ୧⪅ࡢ㛵ಀࡀぢ࠼࡚ࡃࡿ࠿ࡶࡋࢀ࡞࠸ࠋⓎ⌧ࡍࡿࡇ࡜ࡀ☜࠿ࡵࡽࢀ࡚࠸ࡿ 35ࠋ⌧ᅾࠊ୍᪉ࠊศᏊ᣺ືᶵᵓࡸගྠㄪᶵᵓ࡟㛵ࡋ࡚ࡣࠊ㢮ఝ୚ࡍࡿࡇ࡜ࢆ♧၀ࡍࡿ⤖ᯝࢆᚓ࡚࠸ࡿࠋ⯆࿡῝࠸ࡇ࡜࡟ࠊ୺ほⓗኪ๓༙࡛ࡢග࡟ࡼࡿࡇࡢ c-ࡢⅬࡶ࠶ࡿࡀࠊ୧⪅࡛኱ࡁࡃ␗࡞ࡿⅬࡶ࠶ࡿࠋ౛࠼ࡤࠊ

fos/cry ⣔ࢆ௓ࡍࡿ఩┦ᚋ㏥࡟ࡣࠊtim ࡀ㛵୚ࡍࡿࡇ࡜ࣁ࢚࡛ࡣ⬻᫬ィ⣽⬊ࡢගཷᐜศᏊ࡜ࡋ࡚ാࡃ CRY30

ࡀ᫂ࡽ࠿࡟࡞ࡗ࡚ࡁࡓࠋtimRNAi ฎ⌮ಶయࡣࠊ᫂ᬯ࿘

ࡀࠊࢥ࢜ࣟࢠ࡛ࡣศᏊ᣺ືᶵᵓࡢ୰࡛ per/tim ࡜ࡣ⊂ᮇࡢ఩┦๓㐍࡟ࡣྠㄪࡍࡿࡀࠊࡋࡤࡋࡤ఩┦ᚋ㏥࡟ࡣ

❧࡟㈇ࡢࣇ࢕࣮ࢻࣂࢵࢡ࣮ࣝࣉࢆᙧᡂࡋ࡚࠸ࡿⅬ࡛ᛂ⟅࡛ࡁ࡞ࡃ࡞ࡿ㸦ᅗ 7D㸧
ࠋࡉࡽ࡟ࠊࡑࢀࡽࡢಶయࡣ

␗࡞ࡿ 17ࠋࡉࡽ࡟ࠊගྠㄪᶵᵓࡶࣁ࢚࡛ࡣ CRY ࡢගᜏ᫂᮲௳࡟ࡶᛂ⟅࡛ࡁ࡞࠸ࠋࡇࡢࢥ࢜ࣟࢠࡢάືࣜࢬ

ཷᐜ࡟ࡼࡾ TIM ࡀศゎࡉࢀࡿࡇ࡜࡛ࣜࢭࢵࢺࡀ⏕ࡎ࣒ࡣࠊᜏ᫂᮲௳ୗ࡛ࡣ㏻ᖖ 24 ᫬㛫ࡼࡾࡶ࠿࡞ࡾ㛗࠸ࡿࡀࠊࢥ࢜ࣟࢠ࡛ࡣ᏶඲࡟」║࡟౫Ꮡࡋ࡚࠾ࡾࠊCRY࿘ᮇ࡛⮬⏤⥅⥆ࡍࡿࡀࠊtimRNAi ฎ⌮ಶయ࡛ࡣ࿘ᮇࡀ

ࡣ c-fos ࡢୗὶ࡛ാࡃࡇ࡜ 35ࠊ᫂ᮇࡀᘏ㛗ࡉࢀࡓ࡜ࡁ

㏫࡟ 24 ᫬㛫ࡼࡾࡶ▷ࡃ࡞ࡿࠋࡇࡢ⤖ᯝࡣࠊtim ࡀ᫬࡟ࡣ Pdp1 ࡀാࡃࡇ࡜࡞࡝ࡢⅬ࡛␗࡞ࡗ࡚࠸ࡿ 34ࠋྠィࡢ఩┦ᚋ㏥࡟㔜せ࡞ᙺ๭ࢆᢸࡗ࡚࠾ࡾࠊtim ࡢⓎ⌧ࡌ᪻⹸㢮࡞ࡢ࡟ࠊ࡞ࡐࡇࡢࡼ࠺࡞㐪࠸ࡀ࠶ࡿࡢ࠿ࡔࢁ

ᢚไ࡟ࡼࡾ୺ほⓗኪ๓༙ࡢ఩┦ᚋ㏥ࡀḞᦆࡋࠊ୺ほⓗ࠺࠿ࠊࡇࡢࡼ࠺࡞㐪࠸ࡣఱ࡟㉳ᅉࡍࡿࡢࡔࢁ࠺࠿ࠊ࡞ኪᚋ༙ࡢ఩┦๓㐍ࡔࡅࡀ⏕ࡎࡿࡓࡵ࡟ࠊ࿘ᮇࡢ▷⦰ࡀ

࡝࡜ࠊᵝࠎ࡞␲ၥࡀ‪࠸࡚ࡃࡿࡀࠊࡇࢀࡽ࡟ࡘ࠸࡚ࡣ⏕ࡌࡓ࡜ゎ㔘࡛ࡁࡿࠋ௒ᚋࡢ◊✲࡟ࡺࡔࡡࡓ࠸ࠋ⤊ࢃࡾ࡟ㅰ㎡ࢥ࢜ࣟࢠࡢ᫬ィᶵᵓࢆ୰ᚰ࡟᭩࠸࡚ࡁࡓࡀࠊᑡࡋ௚ᴫ᪥᫬ィࡢ◊✲࡬ࡢᡭ࡯࡝ࡁࢆࡋ࡚࠸ࡓࡔ࠸ࡓ༓ࡢ᪻⹸࡜ࡢ㛵㐃ࢆぢ࡚࠾ࡁࡓ࠸ࠋࣁ࢚௨እ࡛᪻⹸ࡢ᫬ⴥ႐ᙪඛ⏕㸦ᒣཱྀ኱Ꮫྡ㄃ᩍᤵ㸧࡟῝ࡃ࠾♩⏦ࡋୖࡆィᶵᵓࡢ◊✲ࢆ≌ᘬࡋ࡚ࡁࡓࡢࡣࠊࢦ࢟ࣈ࡛ࣜ࠶ࡿࠋࡿࠋࡲࡓࠊᒣཱྀ኱Ꮫࠊᒸᒣ኱Ꮫ࡛◊✲ࢆඹ࡟ࡋࡓᏛ⏕ࡑࡢከࡃࡣ Pittendrigh ࡜ࡑࡢඹྠ◊✲⪅ࡢᴗ⦼࡛࠶ㅖẶ࣭༤ኈ◊✲ဨㅖẶ࡟ࡶ῝ࡃ࠾♩⏦ࡋୖࡆࡿࠋᙼࡽࡿࠋ᫬ィࡢᡤᅾࡸ᫬ィ࡟ࡼࡿ⾜ືไᚚ࡟ࡘ࠸࡚ࡣࠊࡢ༠ຊ↓ࡃࡋ࡚ࡣࠊ◊✲ࢆ㐍ࡵࡿࡇ࡜ࡣ฿ᗏ࡛ࡁ࡞࠿

Pittendrigh ࡢᘵᏊ࡟࠶ࡓࡿ Terry Page ࡀඃࢀࡓᡂࡗࡓ࡜ᛮ࠺ࠋศᏊ⏕≀Ꮫⓗ◊✲ࡢ㛤ጞ࡟࠶ࡓࡗ࡚ᵝࠎᯝࢆୖࡆ࡚࠸ࡿࠋᙼࡣどⴥࡢ⛣᳜࡟ࡼࡾࠊどⴥࡀ᫬ィ࡟ຓࡅ࡚࠸ࡓࡔ࠸ࡓࠊᯇᮏ㢧Ặ㸦㡰ኳᇽ኱Ꮫ㸧ࠊ㔝ᆅࡢᗙ࡛࠶ࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡋࡓ 36ࠋࡑࡢ㝿ࠊLD11:11⃈ᬕẶ㸦⌧ᚨᓥ኱Ꮫ㛗㸧࡟ࡣ≉࡟ཌࡃ࠾♩ࢆ⏦ࡋୖࡆ

࡜ LD13:13 ࡢୗ࡛Ⓨ⫱ࡉࡏࠊ࿘ᮇࡀṇᖖಶయࡼࡾࡶ

ࡓ࠸ࠋࡉࡽ࡟ࠊ୍ே୍ேࡢ࠾ྡ๓ࢆୖࡆࡿࡇ࡜ࡣ࡛ࡁ

᫬㛫⏕≀Ꮫ㻌㼂㼛㼘㻚㻞㻣㻘㻌㻺㼛㻚㻌㻞㻌㻔㻞㻜㻞㻝㻕㻥㻜

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