INVOLVEMENT OF ADAPT78 IN DOWN SYNDROME

描述：（根据申请人的描述改编）克劳福德博士 一个实验室最近发现了一些基因， 氧化和其他应激在仓鼠HA-1细胞中使用的方法， 差异显示 当其中一个名为adapt 78的基因被克隆出来， 测序后，发现它与最近报道的基因DSCR 1同源， 位于HSA 21的专性区域，其中与Down相关的基因 综合征、阿尔茨海默氏病和其他神经系统疾病都是局部的。 在 此外，adapt 78/DSCR 1 mRNA在两个脑组织中均有较高的表达， 和心脏，可能与发育有关的智力迟钝， 先天性心脏病是患者的主要临床特征， 唐氏综合症。 因此，adapt 78代表在Down中过表达的基因， 综合征可能会产生特定的致病作用，由于基因剂量在 三体状态 博士Crawford建议在此RO 3应用程序中进行具体研究，以确定 adapt 78是否在唐氏综合征和其他疾病的病因学中起作用 与压力有关的疾病 他建议让NICHD支持 在亚拉巴马的转基因小鼠设施产生表达人 adapt 78，在显微注射人adapt 78的cDNA后， CMV启动子的控制。 然后将通过PCR鉴定为阳性的小鼠 进行研究，以确定它们是否表达adapt 78 mRNA，到什么水平， 以及在哪些组织中。

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.