INVOLVEMENT OF ADAPT78 IN DOWN SYNDROME

描述：(改编自申请者的描述)克劳福德博士的 实验室最近发现了一些基因，这些基因是由 金黄地鼠HA-1细胞氧化应激及其他应激反应的研究 差异显示。当其中一个被命名为Adapt78的基因被克隆并 测序后，发现它与最近报道的基因DSCR1同源， 位于HSA21的专有区域，与Down相关的基因 综合症、阿尔茨海默氏症和其他神经疾病都是局部性的。在……里面 此外，在两个大脑中都发现了Adapt78/DSCR1mRNA的高表达 和心脏，在发育上可能与精神发育迟滞和 先天性心脏病是先天性心脏病患者的主要临床特征 唐氏综合症。因此，Adapt78代表其在Down中过度表达的基因 证候可能因基因剂量的不同而产生特定的致病效应 三体状态。 Crawford博士提出了在R03应用中的具体研究，以确定 Adapt78是否在唐氏综合征和其他疾病的病因中起作用 与压力相关的障碍。他建议让NICHD得到支持 阿拉巴马州的转基因小鼠设施生产出表达人类基因的小鼠 Adapt78，在显微注射人Adapt78的cDNA后，在 CMV启动子的控制。经聚合酶链式反应鉴定为阳性的小鼠 被研究以确定它们是否表达Adapt78mRNA，表达到什么水平， 以及在什么纸巾里。

DESCRIPTION: (Adapted from applicant's description) Dr. Crawford's laboratory has recently identified a number of genes that are induced by oxidative and other stress in hamster HA-1 cells using the method of differential display. When one of these, named adapt78, was cloned and sequenced, it was found to be homologous to a recently reported gene, DSCR1, located in the obligate region of HSA21 where genes associated with Down syndrome, Alzheimer's disease, and other neural disorders are localized. In addition, higher expression of adapt78/DSCR1 mRNA was found in both brain and heart and may be related developmentally to mental retardation and congenital heart disease that are major clinical features of patients with Down syndrome. Thus, adapt78 represents a gene whose overexpression in Down syndrome may produce specific pathogenetic effects due to gene dosage in the trisomic condition. Dr. Crawford proposes specific studies in this RO3 application to determine whether adapt78 plays a role in the etiology of Down syndrome and other stress-related disorders. He proposes to have the NICHD-supported transgenic mouse facility at Alabama generate mice that express human adapt78, following microinjection of a cDNA of human adapt78 under the control of the CMV promoter. Mice identified as positive by PCR will then be studied to determine whether they express adapt78 mRNA, to what level, and in what tissues.