Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Treatment of Dyrk1A-dependent Mental Retardation of Down Syndrome: Isolation of Human Dyrk1A-specific shRNA

다운증후군의 Dyrk1A 의존적 뇌기능저하의 치료: 인간 Dyrk1A 특이적 shRNA 발굴

  • Jung, Min-Su (Institute for Brain Science and Technology (IBST), Graduate Program in Neuroscience, Inje University) ;
  • Kim, Yeun-Soo (Institute for Brain Science and Technology (IBST), Graduate Program in Neuroscience, Inje University) ;
  • Kim, Ju-Hyun (Department of Life Science, Pohang University of Science and Technology) ;
  • Kim, Joung-Hun (Department of Life Science, Pohang University of Science and Technology) ;
  • Chung, Sul-Hee (Institute for Brain Science and Technology (IBST), Graduate Program in Neuroscience, Inje University) ;
  • Song, Woo-Joo (Institute for Brain Science and Technology (IBST), Graduate Program in Neuroscience, Inje University)
  • 정민수 (인제대학교 뇌과학기술연구소) ;
  • 김연수 (인제대학교 뇌과학기술연구소) ;
  • 김주현 (포항공과대학교 생명과학과) ;
  • 김정훈 (포항공과대학교 생명과학과) ;
  • 정설희 (인제대학교 뇌과학기술연구소) ;
  • 송우주 (인제대학교 뇌과학기술연구소)
  • Published : 2009.03.31
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Abstract

Down syndrome (DS) results from overexpressed genes on an extra copy of human chromosome 21. Among various phenotypes seen in DS patients, mental retardation, such as learning and memory deficits, is a major factor that prevents DS individuals from leading fully independent lives. The Dyrk1A gene that plays a critical role in neurodevelopment has been isolated from chromosome 21, and transgenic mice with over-expression of Dyrk1A show severe hippocampal dependent learning and memory defects. In the present study, as an initial step to test the treatment of Dyrk1A dependent mental retardation phenotypes in model animals, we isolated human Dyrk1A specific lentiviral short hairpin RNA (shRNA) that inhibits the exogenous human Dyrk1A expression, but not the endogenous mouse expression in transgenic mice with human Dyrk1A overexpression. This limited and specific repression of exogenous human Dyrk1A will prove to be valuable information, if Dyrk1A dependent learning and memory defects in DS patients could be treated or at least ameliorated in vivo.

다운증후군은 추가적으로 존재하는 인간염색체 21번에 위치한 유전자의 과발현으로 발병한다. 다운증후군 환자에서 보이는 여러 증상들 중 학습과 기억능력 저하와 같은 뇌기능 저하는 다운증후군 환자가 독립적인 생활을 영위하는데 가장 큰 걸림돌이 된다. 인간염색체 21번에 위치하는 Dyrk1A는 신경발달에 중요한 역할을 하는 단백질로 Dyrk1A를 과발현 하는 형질전환 생쥐에서 심각한 해마 의존적 학습과 기억 장애가 보고되었다. 본 연구에서는 인간 Dyrk1A를 과발현 하는 형질전환 생쥐와 RNA interference (RNAi) 방법을 이용하여 endogenous mouse Dyrk1A의 발현은 정상적으로 유지하면서 exogenous human Dyrk1A 발현은 특이적으로 저해함으로써 인간 Dyrk1A 과발현에 의한 학습과 기억 능력저하를 회복시킬 수 있는지 동물모델에서 검증하기 위한 첫 단계로 인간 Dyrk1A 특이적 lentiviral short hairpin RNA (shRNA)를 발굴하였다. 발굴된 shRNA를 이용한 형질전환 모델생쥐에서의 증상의 회복 가능성 검증은 다운증후군의 뇌기능저하 치료제 개발에 중요한 정보를 제공할 것이다.

Keywords

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