KR20010040330A - 유전자 변이동물 - Google Patents
유전자 변이동물 Download PDFInfo
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- KR20010040330A KR20010040330A KR1020007007576A KR20007007576A KR20010040330A KR 20010040330 A KR20010040330 A KR 20010040330A KR 1020007007576 A KR1020007007576 A KR 1020007007576A KR 20007007576 A KR20007007576 A KR 20007007576A KR 20010040330 A KR20010040330 A KR 20010040330A
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- South Korea
- Prior art keywords
- protein
- presenilin
- amino acid
- gene
- mutant
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Abstract
Description
Claims (50)
- 변이 프리세닐린 유전자를 갖는 인간 이외의 유전자 변이동물.
- 제 1항에 있어서,프리세닐린-1 단백질의 아미노산 서열 중 하나의 아미노산이 다른 아미노산으로 치환된 변이 프리세닐린-1 단백질을 코딩하는 DNA 서열을포함하는 변이 프리세닐린-1 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항에 있어서,프리세닐린-1 단백질의 아미노산 서열에 있어서,제 79번, 제 82번, 제 96번, 제 115번, 제 120번, 제 135번, 139번,제 143번, 제 146번, 제 163번, 제 209번, 제 213번, 제 231번, 제235번, 제 246번, 제 250번, 제 260번, 제 263번, 제 264번, 제 267번, 제 269번, 제 280번, 제 285번, 제 286번, 제 290번, 제 318번,제 384번, 제 392번, 제 410번, 제 426번, 및 제 436번으로 이루어지는 군으로부터 선택되는 1 또는 2 이상의 아미노산이 다른 아미노 산으로 치환된 아미노산 서열을 갖는 변이 프리세닐린-1 단백질을 코 딩하는 DNA 서열을 포함하는 프리세닐린-1 변이 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항에 있어서,프리세닐린-1 단백질의 아미노산 서열에 있어서,A79V, V82L, V96F, Y115H, Y115C, E120K, E120D, N135D, M139V,M139T, M139I, I143F, I143T, M146L, M146V, H163Y, H163R, G209V,I213T, A231T, A231V, L235P, A246E, L250S, A260V, C263R, P264L,P267S, R269G, R269G, R269H, E280A, E280G, A285V, L286V, S290C,E318G, G384A, L392V, C410Y, A426P, 및 P436S,(각 알파벳은 일문자표기법에 의한 아미노산을 의미하며, 숫자는 프리세닐린-1 단백질의 N 말단으로부터의 아미노산 번호를 나타내고, 숫자왼쪽에 표시된 야생형의 아미노산이 오른쪽의 아미노산으로 치환됨을나타낸다.)으로 구성되는 군에서 선택되는 1 또는 2 이상의 변이를 갖는 변이 프리세닐린-1 단백질을 코딩하는 DNA 서열을 포함하는 변이 프리세닐린-1 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항에 있어서,프리세닐린-1의 제 213번의 이소류신이 이소류신 이외의 아미노산으로치환된 변이 프리세닐린-1 단백질을 코딩하는 DNA 서열을 포함하는 변이 프리세닐린-1 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항에 있어서,프리세닐린-1의 제 213번의 이소류신이 트레오닌으로 치환된 변이 프리세닐린-1 단백질을 코딩하는 DNA 염기서열을 포함하는 변이 프리세닐린-1 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항 내지 제 6항의 어느 한 항에 있어서,프리세닐린-1 단백질의 아미노산 서열 중 제 213번 아미노산의 부근을코딩하는 DNA 서열이,5'-TGTGGTCGGGATGATMGCC ANC CACTGGAAAGGCCC-3'(단, N은 T 이외의 염기를 의미하고, M은 T 또는 C를 의미하며, 밑줄친 염기가 제 213번의 아미노산을 코딩하는 염기이다.)으로 변이된 변이 프리세닐린-1 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항 내지 제 6항의 어느 한 항에 있어서,프리세닐린-1 단백질의 아미노산 서열 중 제 213번 아미노산의 부근을코딩하는 DNA 서열이,5'-TGTGGTCGGGATGATMGCC ANC CACTGGAAAGGCCC-3'(단, N은 C를 의미하고, M은 T 또는 C를 의미하며, 밑줄친 염기가 제213번의 아미노산을 코딩하는 염기이다.)으로 변이된 변이프리세닐린-1 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항 내지 제 6항의 어느 한 항에 있어서,프리세닐린-1 단백질의 아미노산 서열 중 제 213번 아미노산의 부근을코딩하는 DNA 서열이,5'-TGTGGTCGGGATGATMGCC XYZ CACTGGAAAGGCCC-3'(단, XYZ는 이소류신 이외의 아미노산을 코딩하는 코돈을 의미하고, M은 T 또는 C를 의미하며, 밑줄친 염기가 제 213번 아미노산을 코딩하는 염기이다.)으로 변이된 변이 프리세닐린-1 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항에 있어서,프리세닐린-2 단백질의 아미노산 서열에 있어서, 제 141번 및/또는436번 아미노산이 다른 아미노산으로 치환된 단백질을 코딩하는 DNA서열을 포함하는 변이 프리세닐린-2 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 10항에 있어서,프리세닐린-2 단백질의 아미노산 서열에 있어서, N141I 및/또는M239V(각 알파벳은 일문자표기법에 의한 아미노산을 의미하며, 숫자는프리세닐린-2 단백질의 N 말단으로부터의 아미노산 번호를 나타내고,숫자 왼쪽에 표시된 야생형의 아미노산이 오른쪽의 아미노산으로 치환됨을 나타낸다.)의 변이를 갖는 변이 프리세닐린-2 단백질을 코딩하는DNA 서열을 포함하는 변이 프리세닐린-2 유전자를 갖는인간 이외의 유전자 변이동물.
- 제 1항 내지 제 11항의 어느 한 항에 있어서,아밀로이드 β단백질의 과잉발현이 변이 프리세닐린-1 유전자 및/또는변이 프리세닐린-2 유전자에 기인하는유전자 변이동물.
- 제 1항 내지 제 12항의 어느 한 항에 있어서,변이 프리세닐린 단백질을 발현할 수 있으며, 이 단백질의 발현이 포유동물의 뇌의 대뇌피질 주변부에 있어서 진행성 신경질환을형성시키기에 충분한 양의 아밀로이드 β단백질을 생산시키는 것인인간 이외의 유전자 변이동물.
- 제 1항 내지 제 13항의 어느 한 항에 있어서,유전자 변이동물이 포유류 동물의 설치류인인간 이외의 유전자 변이동물.
- 제 1항 내지 제 14항의 어느 한 항에 있어서,유전자 변이동물이 마우스인인간 이외의 유전자 변이동물.
- 제 1항 내지 제 15항의 어느 한 항에 있어서,변이 프리세닐린-1 유전자 및/또는 변이 프리세닐린-2 유전자가 상동재조합에 의하여 도입된인간 이외의 유전자 변이동물.
- 제 1항 내지 제 16항의 어느 한 항에 있어서,변이 프리세닐린-1 유전자에 의하여 발생된 뇌조직에서의 아밀로이드단백질의 발현량이, 정상동물에 비하여 기억학습 시험에 있어 장애를받은 행동을 일으키고, 해당동물 뇌의 해마의 대뇌피질 주변부에있어서 이상 신경병리를 유발하기에 충분한 것을 특징으로 하는인간 이외의 유전자 변이동물.
- 프리세닐린-1 단백질의 아미노산 서열 중 1 또는 2 이상의 아미노산이 다른 아미노산으로 치환된 변이 프리세닐린-1 단백질을 코딩하는 변이 프레세닐린-1 유전자와 마커 단백질을 코딩하는 염기서열을 포함하는 DNA를 갖는 인간 이외의 유전자 변이동물.
- 프리세닐린-1 단백질의 아미노산 서열 중 제 213번 아미노산의 부근을 코딩 하는 DNA 서열이,5'-TGTGGTCGGGATGATMGCC ANC CACTGGAAAGGCCC-3'(단, N은 A, G 또는 C를 의미하고, M은 T 또는 C를 의미하며, 밑줄친 염기가 제 213번의 아미노산을 코딩하는 염기이다.)인 변이 프리세닐린-1 유전자의 DNA 서열 또는 그 부분서열을 포함하는 플라스미드.
- 프리세닐린-1 단백질의 아미노산 서열 중 제 213번 아미노산이 이소류신 이외의 아미노산으로 치환된 변이 프리세닐린-1 단백질을 코딩하는 변이 프리세닐린-1 유전자이고, 제 213번 아미노산의 부근을 코딩하는 DNA 서열이,5'-TGTGGTCGGGATGATMGCC XYZ CACTGGAAAGGCCC-3'(단, M은 T 또는 C를 의미하며, XYZ는 이소류신 이외를 코딩하는 3염기의 코돈을 의미하고, 밑줄친 염기가 제 213번의 아미노산을 코딩하는 염기이다.)인 유전자의 DNA 서열 또는 그 부분서열을 포함하는 플라스미드.
- 프리세닐린-1 단백질의 아미노산 서열 중 제 213번의 아미노산이 이소류신 이외의 아미노산으로 치환된 변이 프리세닐린-1 단백질을 코딩하는 변이 프리세닐린-1 유전자의 엑손 8을 포함하는 염색체 DNA.
- 프리세닐린-1 단백질의 아미노산 서열 중 제 213번 아미노산이 이소류신 이외의 아미노산으로 치환된 변이 프리세닐린-1 단백질을 코딩하는 변이 프리세닐린-1 유전자의 cDNA 또는 염색체 DNA의 전장 또는 변이부분을 함유하는 염기서열에 대하여 Sau3AI 부위가 도입된 DNA를 함유하는 플라스미드.
- 제 22항에 있어서,아미노산의 치환이 213번의 이소류신에서 트레오닌으로의 치환인플라스미드.
- 하기 염기서열:5'-TGTGGTCGGGATGATMGCCACCCACTGGAAAGGCCC-3'(여기서, M은 T 또는 C를 의미한다.)로 특정지워지는 DNA를 함유하는 플라스미드.
- 마우스·프리세닐린-1 단백질의 아미노산 서열 제 213번의 이소류신이 이소류신 이외의 아미노산으로 치환된 마우스 변이 프리세닐린-1 단백질을 코딩하는 DNA 서열을 포함하는 유전자.
- 제 25항에 있어서,아미노산의 치환이 이소류신에서 트레오닌으로의 치환인유전자.
- (1) 마우스·프리세닐린-1 단백질의 아미노산 서열의 제 213번의 이소류신이 이소류신 이외의 아미노산으로 치환된 마우스 변이 프리세닐린-1 단백질을 코딩하는 유전자, 및 (2) loxP가 양옆에 위치한(flanking) 네오마이신 발현 유닛을 포함하는 플라스미드.
- 제 27항에 있어서,아미노산의 치환이 이소류신에서 트레오닌으로의 치환인플라스미드.
- 하기 염기서열:5'-TGTGGTCGGGATGATMGCCACCCACTGGAAAGGCCC-3'(여기서, M은 T 또는 C를 의미한다.)로 특정지워지는 DNA를 함유하는 플라스미드가 도입된 것을 특징으로 하는 배.
- 제 20항, 22항, 23항, 24항, 27항, 또는 28항의 플라스미드를 이용한 상동 재조합으로 얻어진 배.
- 제 29항 또는 제 30항에 있어서,배가 포유류 동물의 설치류 유래의 배인배.
- 제 29항 내지 제 31항의 어느 한 항에 있어서,마우스 유래의 배성간세포인배.
- 제 1항 내지 제 18항의 어느 한 항에 기재된 유전자 변이동물의 세포를 분리하고, 조직배양에 의하여 배양함으로써 얻어지는 초대배양세포 또는 계대배양세포.
- 변이 프리세닐린-1 단백질을 발현할 수 있으며, 이 단백질의 발현이 뇌의 해마 또는 대뇌피질 주변부에 있어서 진행성 신경질환을 형성시키기에 충분한 양의 아밀로이드 β단백질을 생산시킬 수 있는 변이 프리세닐린-1 유전자를 상동 재조합법에 의하여 동물의 배에 도입하는 공정을 포함하는, 인간 이외의 유전자 변이동물의 작제방법.
- 제 34항에 기재된 유전자 변이동물의 작제방법에 있어서, 제 213번의 이소류신이 이소류신 이외의 아미노산으로 치환된 변이 프리세닐린-1 변이 단백질을 발현하는 방법.
- 피검물질을 투여한 제 1항 내지 제 18항의 어느 한 항 기재의 유전자 변이동물과 무투여 또는 대조물질을 투여한 동물을 비교하는 공정을 포함하는 알츠하이머병의 치료법 및/또는 예방에 유용한 물질의 평가방법.
- 제 36항에 있어서,기억학습시험에 의하여 비교하는평가방법.
- 제 36항에 있어서,병리시험에 의하여 비교하는평가방법.
- 제 36항에 있어서,대뇌피질 주변부에서의 신경병리에 근거한 병리시험에 의하여비교하는평가방법.
- 제 38항 또는 제 39항에 있어서,신경병리에 근거한 병리시험에 의한 비교가 해당뇌의 대뇌피질 주변부에서의 비대한 신경교종(glyosis) 감소의 억제, 해당뇌의 대뇌피질 주 변부에서의 2-디옥시글루코스 획득감소의 억제, 및 해당뇌의 대뇌피질 에서의 2-디옥시글루코스 이용감소의 억제로 구성되는 군에서 선택되 어지는 1 또는 2 이상의 항목의 비교인평가방법.
- 제 36항에 있어서,해당동물의 생존기간, 탐색행동, 및 이동행동으로 구성된 군에서 선택되는 1 또는 2 이상의 항목에 대하여 비교하는평가방법.
- 제 33항에 기재된 초대배양세포 또는 계대배양세포를 피검화합물의 존재하에 시험관내(in vitro) 세포배양하는 공정을 포함하는 알츠하이머병의 치료 및/또는 예방제의 평가방법.
- OS-2형 변이 프리세닐린-1 단백질을 코딩하는 변이 프레세닐린-1 유전자의 부분염기서열을 이용하는 것을 특징으로 하는 알츠하이머병 또는 알츠하이머병의 발병 가능성의 진단방법.
- 제 36항 내지 제 42항의 어느 한 항에 기재된 평가방법에 의하여 선택되어진 알츠하이머병의 치료 및/또는 예방에 유용한 물질.
- 제 44항에 기재된 물질을 유효성분으로 함유하는 알츠하이머병의 치료 및/또는 예방제.
- 제 1항 내지 제 18항의 어느 한 항에 기재된 유전자 변이동물과 아밀로이드 전구체 단백질(APP)의 변이 단백질을 코딩하는 유전자를 가지며, 아밀로이드 β단백질의 생산량이 많은 동물을 교배시켜 작제한 하이브리드 동물 및 그 자손으로, 변이 프리세닐린 유전자와 아밀로이드 전구체 단백질의 변이 단백질을 코딩하는 유전자를 갖는 유전자 변이동물.
- 제 46항에 있어서,동물이 마우스인유전자 변이동물.
- 제 47항에 있어서,아밀로이드 전구체 단백질을 코딩하는 유전자를 가지며, 아밀로이드β단백질의 생산량이 많은 마우스가 PS1 변이된 마우스인유전자 변이동물.
- 제 7항 내지 제 18항의 어느 한 항에 기재된 유전자 변이동물과 아밀로이드 전구체 단백질을 코딩하는 유전자를 가지며, 아밀로이드 β단백질의 생산량이 많은 마우스를 교배하여 작제한 하이브리드 마우스 및 그 자손으로, 변이 프리세닐린 유전자와 아밀로이드 전구체 단백질의 변이 단백질을 코딩하는 유전자를 갖는 유전자 변이 마우스.
- 제 7항 내지 제 18항의 어느 한 항에 기재된 유전자 변이동물과 아밀로이드 전구체 단백질을 코딩하는 유전자를 가지며, 아밀로이드 β단백질의 생산량이 많은 마우스를 교배하여 태어난 하이브리드 마우스 및 그 자손으로, 변이 프리세닐린 유전자와 아밀로이드 전구체 단백질의 변이 단백질을 코딩하는 유전자를 갖는 유전자 변이 마우스.
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US11266129B2 (en) | 2019-11-05 | 2022-03-08 | Versiti Blood Research Institute Foundation, Inc. | Murine model of fetal/neonatal alloimmune thrombocytopenia |
EP4054324A1 (en) | 2019-11-05 | 2022-09-14 | Versiti Blood Research Institute Foundation, Inc. | A murine model of fetal/neonatal alloimmune thrombocytopenia |
RU2757114C1 (ru) * | 2020-08-05 | 2021-10-11 | Федеральное государственное бюджетное учреждение науки Институт биологии гена Российской академии наук | Способ получения линии гуманизированных мышей, трансгенных по hACE2 |
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JP3019344B2 (ja) | 1988-04-15 | 2000-03-13 | エヌ・イー・エヌ・ライフ・サイエンス・プロダクツ・インコーポレイテツド | 95kb程度の大きさのdna断片用p1バクテリオフアージクローニング系 |
US5650550A (en) * | 1993-10-01 | 1997-07-22 | The United States Of America As Represented By The Department Of Health And Human Services | Mutant mice having a deficit of functional estrogen receptors |
US5877399A (en) | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
US5986054A (en) * | 1995-04-28 | 1999-11-16 | The Hospital For Sick Children, Hsc Research And Development Limited Partnership | Genetic sequences and proteins related to alzheimer's disease |
JP2001514528A (ja) * | 1997-05-14 | 2001-09-11 | メルク エンド カンパニー インコーポレーテッド | 天然プレセニリン1ヌルバックグラウンド上で非天然野生型および家族性アルツハイマー病突然変異プレセニリン1タンパク質を発現するトランスジェニック動物 |
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1999
- 1999-01-07 CN CN998037990A patent/CN1292638A/zh active Pending
- 1999-01-07 JP JP2000527142A patent/JP4290329B2/ja not_active Expired - Lifetime
- 1999-01-07 EP EP99900133A patent/EP1044605B1/en not_active Expired - Lifetime
- 1999-01-07 RU RU2000120677/13A patent/RU2266002C2/ru active
- 1999-01-07 WO PCT/JP1999/000015 patent/WO1999034670A1/ja active IP Right Grant
- 1999-01-07 KR KR1020007007576A patent/KR100646816B1/ko not_active IP Right Cessation
- 1999-01-07 DE DE69935903T patent/DE69935903T2/de not_active Expired - Lifetime
- 1999-01-07 AU AU17844/99A patent/AU1784499A/en not_active Abandoned
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- 1999-01-07 US US09/581,528 patent/US7022893B1/en not_active Expired - Lifetime
- 1999-01-08 TW TW094110822A patent/TW200529742A/zh unknown
- 1999-01-08 TW TW088100217A patent/TWI240752B/zh not_active IP Right Cessation
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2000
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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KR100462180B1 (ko) * | 2001-11-20 | 2004-12-16 | (주) 디지탈바이오텍 | 알츠하이머병 병인 유전자로 형질전환된 동물 및 그 제조방법 |
KR100584914B1 (ko) * | 2004-03-30 | 2006-05-30 | 주식회사 뉴로테크 | 돌연변이 app를 발현하는 알츠하이머병 유발 형질전환마우스 |
KR20220040573A (ko) * | 2020-09-23 | 2022-03-31 | 재단법인대구경북과학기술원 | 알츠하이머 동물모델 및 이의 용도 |
WO2023282552A1 (ko) * | 2021-07-08 | 2023-01-12 | 주식회사 엠케이바이오텍 | Human mutant presenilin-1 발현 인지장애 모델 개의 생산 |
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EP1044605B1 (en) | 2007-04-25 |
TW200529742A (en) | 2005-09-16 |
JP4290329B2 (ja) | 2009-07-01 |
NO20003495D0 (no) | 2000-07-07 |
AU1784499A (en) | 1999-07-26 |
EP1044605A4 (en) | 2003-05-07 |
EP1044605A1 (en) | 2000-10-18 |
TWI240752B (en) | 2005-10-01 |
DE69935903T2 (de) | 2008-01-10 |
KR100646816B1 (ko) | 2006-11-17 |
WO1999034670A1 (fr) | 1999-07-15 |
NO20003495L (no) | 2000-09-07 |
RU2266002C2 (ru) | 2005-12-20 |
DE69935903D1 (de) | 2007-06-06 |
CN1292638A (zh) | 2001-04-25 |
HK1031983A1 (en) | 2001-07-06 |
US7022893B1 (en) | 2006-04-04 |
CA2317809A1 (en) | 1999-07-15 |
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