英国等国的科学家通过老鼠实验最新证实，一个名为DISC1的基因发生突变会导致老鼠出现精神分裂症或抑郁症症状。
由英国等国科学家组成的科研小组通过大规模筛选，分离出了老鼠体内DISC1基因两种不同的变异版本。结果发现，其中一种变异版本的老鼠表现出的行
为异常、记忆力受损等症状，与人类的精神分裂症症状类似，而且服用抗精神分裂症的药物后，老鼠的这些症状会减轻。另外一种变异版本的老鼠则表现出抑郁症的诸多症状，通过服用抗抑郁症药物，它们的症状也得到了缓解。
研究小组还发现，这两种版本的DISC1基因变异使老鼠的脑容量都出现减少现象，而一般患有精神分裂症和抑郁症的人，脑容量也会有不同程度的下降。另外，这两类老鼠体内由DISC1基因编码的一种蛋白质也均出现了生化功能异常。
他们的研究成果发表在5月3日出版的美国《神经元》Neuron杂志上。
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.
