DRPLAノックアウトマウスにおける遺伝子発現プロファイリング
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概要
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DRPLA (dentatorubral-pallidoluysian atrophy) is an autosomal dominant neurodegenerative disorder characterized by various combinations of cerebellar ataxia, choreoathetosis, myoclonus, epilepsy, mental retardation and dementia. Neuropathological findings show selective neuronal loss in dentate nucleus, red nucleus, globus pallidus and subthalamic nucleus. DRPLA is one of the neurodegenerative disorders caused by expanded polyglutamine (polyQ) stretches in DRPLA/atrophin-1. The physiological function of the DRPLA/atrophin-1 remains unknown. Recent studies showed DRPLA/atrophin-1 might function as a transcriptional factor, particularly a transcriptional co-represser in early developmental stage of Drosophila. To gain insight into the physiological roles of the DRPLA/atrophin-1, we compared expression profiles of approximately 12,000 genes between the brains of DRPLA deficient mice and those of wild-type mice (embryonic 14 days (E14), postnatal 1 day (Pi), 42 days (P42) of age), using oligonucleotide DNA arrays (GeneChip Murine Genome U74Av2; Affymetrix). We detected 192 down-regulated and 242 up-regulated genes at E14, 21 down-and 21 up-regulated genes at P1, and 26 down-and 101 up-regulated genes at P42 in the brains of DRPLA deficient mice. Moreover, we detected 3 genes (Efnb2, 2610042L04Rik, 4930577M16Rik) up and 5 genes (Npy, Ttr, Polr2k, Ociad1, Sfrs2, 1110008H02Rik) down regulated concurrently. These are neuropeptide, thyroid hormone transporter, transcription activator, blood vessel formation related, synapse formation related and RNA processing related protein. These results demonstrate that the lack of the DRPLA/atrophin-1 directly or indirectly changes expression level of a specific group of genes, and that we may harmlessly treat DRPLA by RNAi knockdown technique.
- 新潟大学の論文
- 2005-11-10