KR101655486B1 - 헤르페스 바이러스의 잠복 감염에 관여하는 인자 및 그 이용 - Google Patents
헤르페스 바이러스의 잠복 감염에 관여하는 인자 및 그 이용 Download PDFInfo
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- KR101655486B1 KR101655486B1 KR1020107008198A KR20107008198A KR101655486B1 KR 101655486 B1 KR101655486 B1 KR 101655486B1 KR 1020107008198 A KR1020107008198 A KR 1020107008198A KR 20107008198 A KR20107008198 A KR 20107008198A KR 101655486 B1 KR101655486 B1 KR 101655486B1
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Abstract
Description
도 2는 HHV-6 유전자 산물의 PCR법에 의한 증폭의 결과를 나타내는 도면이다.
도 3은 신규 잠복 감염 특이적 유전자 mRNA의 RACE법에 의한 해석의 결과를 나타내는 도면이다.
도 4는 Yeast Two-hybrid법에 의해, 단백질 SITH-1에 결합하는 숙주 단백질을 동정한 결과를 나타내는 도면이다.
도 5는 단백질 SITH-1에 의해서 아스트로사이트 모양 글리아 세포주내 CAML의 증가를 나타내는 도면이다.
도 6은 SITH-1에 의한 글리아 세포내 칼슘 농도의 상승을 나타내는 도면이다.
도 7은 정신 장애를 가지는 환자의 SITH-1에 대한 항체가를 나타내는 도면이다.
도 8은 미현수(尾懸垂) 테스트에 의한 SITH-1의 효과의 검토 결과를 나타내는 도면이다.
도 9는 강제 수영 테스트에 의한 SITH-1의 효과의 검토 결과를 나타내는 도면이다.
도 10은 경악 반응(Prepulse inhibition)에 의한 SITH-1의 효과의 검토 결과를 나타내는 도면이다.
도 11은 SITH-1을 아데노 바이러스 벡터에 의해 마우스의 글리아 세포에서 발현시켜, 3주일 후에 활차 회전으로 자발 운동량을 측정한 결과를 나타내는 도면이다.
도 12는 SITH-1을 렌티 바이러스 벡터에 의해 마우스의 글리아 세포에서 발현시켜, 8주일 후에 활차 회전으로 자발 운동량을 측정한 결과를 나타내는 도면이다.
도 13은 SITH-1을 지표로 하여, 우울증을 병발하는 다른 질환에 관하여 진단한 결과를 나타내는 도면이다.
Claims (28)
- 이하의 (a), (b), 또는 (c)에 기재된 유전자.
(a) 서열번호 1로 표시되는 아미노산 서열로 이루어지는 단백질을 코드하는 유전자;
(b) 서열번호 2로 표시되는 염기 서열을 오픈 리딩 프레임 영역으로서 가지는 유전자; 또는
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질을 코드하는 유전자로서, 상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인 것. - 이하의 (a) 또는 (b)에 기재된 단백질.
(a) 서열번호 1로 표시되는 아미노산 서열로 이루어지는 단백질;
(b) 제 1항에 기재된 유전자에 의해 코드되는 단백질. - 제 1항에 기재된 유전자를 포함하는 재조합 발현 벡터.
- 제 1항에 기재된 유전자 또는 제 3항에 기재된 재조합 발현 벡터를 도입하여 이루어지고, 인간을 제외하는 형질 전환체.
- 제 1항에 기재된 유전자에 있어서의 염기 서열 또는 그 상보 서열을 가지는 프로브를 포함하는, 유전자 검출기구.
- 제 2항에 기재된 단백질을 포함하는, 상기 단백질을 인식하는, 항체 검출용 검출기구.
- 분리된 생물학적 시료를 이용하여 피험자가 우울증 또는 조울증을 가지는지 여부를 진단하기 위한 정보 취득 방법으로서,
(i) 피험자로부터 분리된 생물학적 시료중에서 단백질을 인식하는 항체의 양 또는 레벨을 판정하는 판정 과정과,
(ii) 생물학적 시료중의 항체의 양을 나타내는 정량치를 지표로서 사용하여 피험자가 우울증 또는 조울증을 가지는지 여부를 판정하는 판정 과정을 포함하고,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 정보 취득 방법. - 인간을 제외한 피험동물이 우울증 또는 조울증을 가지는지 여부를 진단하는 진단 방법으로서,
(i) 단백질을 인식하는 항체가 인간을 제외한 피험 동물에 존재하고 있는지 여부를 판정하는 판정 과정과,
(ii) 상기 판정 과정에서, 단백질을 인식하는 항체가 존재하고 있다고 판정되었을 경우, 상기 인간을 제외한 피험동물이 우울증 또는 조울증을 가진다고 판정하는 판정 과정을 포함하고,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 진단 방법. - 제 7항에 기재한 정보 취득 방법을 실시하는 키트로서,
(i) 단백질; 및
(ii) 단백질 (i)을 고정화한 검출기구
로부터 선택되는 적어도 1개를 포함하고,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 키트. - 제 8항에 기재한 진단 방법을 실시하는 진단 키트로서,
(i) 단백질; 및
(ii) 단백질 (i)을 고정화한 검출기구
로부터 선택되는 적어도 1개를 포함하고,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 진단 키트. - 인간을 제외한 피험동물이 우울증 또는 조울증의 모델 동물로서 유용한지 여부를 판정하기 위한 인간을 제외한 모델 동물의 판정 방법으로서,
(i) 단백질을 인식하는 항체가 인간을 제외한 동물에 존재하고 있는지 여부를 판정하는 판정 과정과,
(ii) 상기 판정 과정에 있어서, 항체가 인간을 제외한 피험 동물에 존재한다고 판정되었을 경우, 인간을 제외한 피험 동물이 우울증 또는 조울증의 인간을 제외한 피험 동물로서 유용하다고 판정하는 판정 과정을 포함하고,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 모델 동물의 판정 방법. - 단백질을 코드하는 유전자, 또는 그 유전자를 가지는 재조합 발현 벡터를 도입하여 이루어지는 인간을 제외한 우울증 또는 조울증의 모델 동물로서,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 모델 동물. - 향정신약 또는 항정신병약의 후보 물질을 스크리닝하는 스크리닝 방법으로서,
(i) 제 12항에 기재된 인간을 제외한 우울증 또는 조울증의 모델 동물에 피험물질을 주는 과정과,
(ii) 행동 이상(異常)에 관한 시험 또는 뇌기능 시험의 결과, 우울증 또는 조울증이 치유 또는 개선된 경우에, 상기 후보 물질이 항정신 장애 작용을 갖는다고 판정하는 판정 과정을 포함하는, 스크리닝 방법. - 피험 대상 생물로부터 분리된 생물학적 시료중에서 단백질을 인식하는 항체를 검출하는 검출과정을 포함하고,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 우울증 또는 조울증 또는 크론병에 기인하는 정신 질환의 진단을 위한 항체 검출 방법. - 피험 대상 생물로부터 분리된 생물학적 시료의 사용을 통하여 피험 대상 생물이 우울증 또는 조울증을 가지는지 여부를 진단하기 위한 정보 취득 방법으로서,
(i) 피험 대상 생물로부터 분리된 생물학적 시료중에서 단백질을 코드하는 유전자 또는 단백질의 양을 판정하는 판정 과정과,
(ii) 생물학적 시료중의 단백질 또는 유전자의 양을 나타내는 정량치를 지표로서 사용하여 피험 대상 생물이 우울증 또는 조울증을 가지는지 여부를 판정하는 판정 과정을 포함하고,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 정보 취득 방법. - 피험 대상 생물이 우울증 또는 조울증을 가지는지 여부를 진단하기 위한 진단 시약을 제조하는 방법으로서,
단백질, 상기 단백질을 코드하는 유전자, 또는 상기 단백질을 확인하는 항체를 사용하여, 상기 진단 시약을 제조하는 공정을 포함하며,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 진단 시약 제조 방법. - 분리된 생물학적 시료의 사용을 통하여 피험자가 우울증 또는 조울증 또는 크론병에 기인하는 정신 질환을 가지는지 여부를 진단하기 위한 정보 취득 방법으로서,
(i) 피험자로부터 분리된 생물학적 시료중에서 단백질을 인식하는 항체의 양을 판정하는 판정 과정과,
(ii) 생물학적 시료중의 항체의 양을 나타내는 정량치를 지표로서 사용하여 피험자가 크론병에 기인하는 정신 질환을 가지는지 여부를 판정하는 판정 과정을 포함하고,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 정보 취득 방법. - 단백질을 코드하는 유전자 또는 그 유전자를 포함하는 재조합 발현 벡터를 인간을 제외한 동물에 도입하는 도입과정을 포함하는, 인간을 제외한 우울증 또는 조울증 또는 크론병에 기인하는 정신 질환의 모델 동물 제조 방법으로서,
상기 단백질은,
(a) 서열번호 1로 표시되는 아미노산 서열을 포함하는 단백질;
(b) 서열번호 2로 표시되는 염기 서열로 이루어지는 오픈 리딩 프레임 영역을 포함하는 폴리뉴클레오티드에 의해 코드되는 단백질; 및
(c) 서열번호 2로 표시되는 염기 서열로 이루어지는 DNA와 상보적인 염기 서열로 이루어지는 DNA와 스트린젠트한 하이브리다이제이션 조건하에서 하이브리다이즈하는 폴리뉴클레오티드에 의해 코드되고, 또한 세포내 칼슘 농도를 상승시키는 활성 또는 칼슘-모듈레이팅 시클로필린 리간드(CAML)와 결합하는 활성을 가지는 단백질
로부터 선택되고,
상기 스트린젠트한 하이브리다이제이션 조건은, 하이브리다이제이션 용액(50% 포름아미드, 5×SSC(150mM의 NaCl, 15mM의 시트르산삼나트륨), 50mM의 인산나트륨(pH7.6), 5×덴헐트(Denhert)액, 10% 황산덱스트란, 및 20㎍/ml의 변성 전단 연어 정자 DNA를 포함한다) 중에서 42℃에서 하룻밤 인큐베이션한 후, 65℃에서 0.1×SSC 중에서 필터를 세정하는 조건인, 모델 동물 제조 방법. - 삭제
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BRPI1015458A2 (pt) * | 2009-03-31 | 2016-04-19 | Japan Tobacco Inc | método para detectar anticorpo contra sith-1 em amostra biológica |
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