英國(guó)等國(guó)的科學(xué)家通過(guò)老鼠實(shí)驗(yàn)最新證實(shí),，一個(gè)名為DISC1的基因發(fā)生突變會(huì)導(dǎo)致老鼠出現(xiàn)精神分裂癥或抑郁癥癥狀,。
由英國(guó)等國(guó)科學(xué)家組成的科研小組通過(guò)大規(guī)模篩選，分離出了老鼠體內(nèi)DISC1基因兩種不同的變異版本,。結(jié)果發(fā)現(xiàn),，其中一種變異版本的老鼠表現(xiàn)出的行
為異常、記憶力受損等癥狀,，與人類(lèi)的精神分裂癥癥狀類(lèi)似,，而且服用抗精神分裂癥的藥物后，老鼠的這些癥狀會(huì)減輕,。另外一種變異版本的老鼠則表現(xiàn)出抑郁癥的諸多癥狀,，通過(guò)服用抗抑郁癥藥物，它們的癥狀也得到了緩解,。
研究小組還發(fā)現(xiàn),，這兩種版本的DISC1基因變異使老鼠的腦容量都出現(xiàn)減少現(xiàn)象，而一般患有精神分裂癥和抑郁癥的人,，腦容量也會(huì)有不同程度的下降,。另外，這兩類(lèi)老鼠體內(nèi)由DISC1基因編碼的一種蛋白質(zhì)也均出現(xiàn)了生化功能異常,。
他們的研究成果發(fā)表在5月3日出版的美國(guó)《神經(jīng)元》Neuron雜志上,。
Behavioral Phenotypes of Disc1 Missense Mutations in Mice
Steven J. Clapcote, Tatiana V. Lipina, J. Kirsty Millar, Shaun Mackie, Sheila Christie, Fumiaki Ogawa, Jason P. Lerch, Keith Trimble, Masashi Uchiyama, Yoshiyuki Sakuraba, Hideki Kaneda, Toshihiko Shiroishi, Miles D. Houslay, R. Mark Henkelman, John G. Sled, Yoichi Gondo, David J. Porteous, and John C. Roder
To support the role of DISC1 in human psychiatric disorders, we identified and analyzed two independently derived ENU-induced mutations in Exon 2 of mouse Disc1. Mice with mutation Q31L showed depressive-like behavior with deficits in the forced swim test and other measures that were reversed by the antidepressant bupropion, but not by rolipram, a phosphodiesterase-4 (PDE4) inhibitor. In contrast, L100P mutant mice exhibited schizophrenic-like behavior, with profound deficits in prepulse inhibition and latent inhibition that were reversed by antipsychotic treatment. Both mutant DISC1 proteins exhibited reduced binding to the known DISC1 binding partner PDE4B. Q31L mutants had lower PDE4B activity, consistent with their resistance to rolipram, suggesting decreased PDE4 activity as a contributory factor in depression. This study demonstrates that Disc1 missense mutations in mice give rise to phenotypes related to depression and schizophrenia, thus supporting the role of DISC1 in major mental illness.
