INVOLVEMENT OF ADAPT78 IN DOWN SYNDROME

ADAPT78 与唐氏综合症的关系

• 批准号: 2555863
• 负责人: DANA R CRAWFORD
• 金额: $ 7.75万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2555863
• 关键词: Downs syndrome; complementary DNA; cytomegalovirus; disease /disorder etiology; genetic promoter element; genetically modified animals; human genetic material tag; laboratory mouse; polymerase chain reaction; protein structure function; stress proteins; virus genetics

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.

描述：（根据申请人的描述改编）克劳福德博士 实验室最近确定了许多由 仓鼠HA-1细胞中的氧化和其他应力，使用 差分显示。 当其中一个名为Adapt78时，被克隆了， 经测序，发现它与最近报道的基因DSCR1同源 位于HSA21的强制性区域中 综合征，阿尔茨海默氏病和其他神经疾病是局部的。 在 此外，在两个大脑中都发现了ADAPT78/DSCR1 mRNA的较高表达 和心脏，可能与智力障碍和 先天性心脏病是患者的主要临床特征 唐氏综合症。 因此，Adapt78代表一个基因，其在下降中的过表达 综合征可能由于基因剂量而产生特定的致病作用 三化状况。 Crawford博士在此RO3应用中提出了具体研究，以确定 Adapt78是否在唐氏综合症的病因和其他 与压力有关的疾病。 他建议让NICHD支持 阿拉巴马州的转基因小鼠设施产生表达人的小鼠 Adapt78，在对人类Adapt78的cDNA进行了微注射之后。 控制CMV启动子。 然后，由PCR鉴定为阳性的小鼠将 进行研究以确定它们是否表达Adapt78 mRNA，哪个水平， 以及在什么组织中。