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KMID : 0613820090190030317
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Journal of Life Science
2009 Volume.19 No. 3 p.317 ~ p.321
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Treatment of Dyrk1A-dependent Mental Retardation of Down Syndrome: Isolation of Human Dyrk1A-specific shRNA
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Jung Min-Su
Kim Yeun-Soo
Kim Ju-Hyun
Kim Joung-Hun
Chung Sul-Hee
Song Woo-Joo
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Abstract
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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.
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KEYWORD
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Down syndrome, Dyrk1A, mental retardation, RNA interference, lentivirus
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