Austin C P, Ky B, Ma L, Morris J A, Shughrue P J
Department of Neuroscience, Merck Research Laboratories, WP26A-3000, PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, USA.
Neuroscience. 2004;124(1):3-10. doi: 10.1016/j.neuroscience.2003.11.010.
DISC1 (Disrupted-In-Schizophrenia 1) has been associated with schizophrenia in multiple genetic studies. Studies from our laboratory have shown that Disc1, the mouse ortholog of DISC1, is highly expressed in the dentate gyrus of the hippocampus in the adult mouse brain. Because developmental dysfunction of the hippocampus is thought to play a major role in schizophrenia pathogenesis, and the dentate gyrus is a major locus for adult neurogenesis in the mouse, we investigated Disc1 expression during mouse brain development. Strikingly, Disc1 is strongly expressed in the hippocampus during all stages of hippocampal development, from embryonic day 14 through adulthood. Disc1 mRNA was detected in the dentate gyrus at all stages in which this structure was identifiable, as well as in the cornu ammonis (CA) fields of the hippocampus, the subiculum and adjacent entorhinal cortex, and the developing cerebral neocortex, hypothalamus, and olfactory bulbs, all of which also express Disc1 in the adult mouse brain. In addition, Disc1 mRNA was seen in regions of the developing mouse brain which do not express Disc1 during adulthood, regions including the bed nucleus of the stria terminalis, reticular thalamic nucleus and reuniens thalamic nucleus. These results demonstrate that Disc1 marks the hippocampus from its earliest stages, and suggest that developmental Disc1 dysfunction may lead to defects in hippocampal function that are associated with schizophrenia.
精神分裂症断裂基因1（DISC1）在多项基因研究中都与精神分裂症相关。我们实验室的研究表明，DISC1在成年小鼠大脑海马齿状回中高表达，其小鼠直系同源基因Disc1也如此。由于海马发育功能障碍被认为在精神分裂症发病机制中起主要作用，且齿状回是成年小鼠神经发生的主要部位，我们研究了小鼠大脑发育过程中Disc1的表达情况。令人惊讶的是，从胚胎第14天到成年期，在海马发育的所有阶段，Disc1在海马中均强烈表达。在齿状回可识别的所有阶段，以及海马的海马角（CA）区、海马下脚和相邻的内嗅皮质、发育中的大脑新皮质、下丘脑和嗅球中均检测到Disc1 mRNA，在成年小鼠大脑中这些区域也都表达Disc1。此外，在成年期不表达Disc1的发育中小鼠大脑区域，包括终纹床核、丘脑网状核和丘脑连合核中也可见Disc1 mRNA。这些结果表明，Disc1从海马发育的最早阶段就开始标记海马，提示发育过程中Disc1功能障碍可能导致与精神分裂症相关的海马功能缺陷。
