MOLECULAR ANALYSIS OF A HERMANSKY-PUDLAK SYNDROME GENE

赫曼斯基-普德拉克综合征基因的分子分析

• 批准号: 6179010
• 负责人: RICHARD T SWANK
• 金额: $ 21.96万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6179010
• 关键词: albinism; artificial chromosomes; autoradiography; complementary DNA; denaturing gradient gel electrophoresis; gene complementation; gene expression; gene mutation; genetic mapping; genetic regulation; granule; human genetic material tag; laboratory mouse; lysosomes; melanocyte; molecular cloning; northern blottings; nucleic acid sequence; platelet disorder; polymerase chain reaction; scintillation counter; single strand conformation polymorphism; southern blotting; western blottings

DESCRIPTION (Adapted from applicant's abstract): The inherited human syndromes of oculocutaneous albinism and in particular the subform termed Hermansky Pudlak Syndrome (HPS) cause considerable morbidity and mortality, yet knowledge of the genes which cause the syndrome and efficacious treatments are minimal. In contrast, studies in the mouse have identified at least 14 different genes which directly cause HPS. The broad long-term objective of this research is to utilize the genetic advantages of the mouse to clone and characterize the mouse HPS and corresponding human homologs to better understand the causes and ultimately devise therapies for severe forms of human HPS. In particular, it is proposed to clone and partially characterize one of the more defined mouse HPS genes, ruby eye. The ruby eye gene has intrinsic interest, not only because it causes HPS, but also because it regulates the biogenesis/processing/secretion of three subcellular organelles; melanosomes, lysosomes and platelet dense granules. The specific aims of the proposal are to: (1) identify the mouse ruby eye (ru) gene by positional/candidate gene approaches; (2) isolate the human homolog corresponding to the ruby eye cDNA and test for alteration in this gene in HPS kindreds; and (3) partially characterize the expression and regulation of the mouse ruby eye gene.

描述（改编自申请人的摘要）：继承的人类 眼皮白化症的综合征，尤其是所谓的子形式 Hermansky Pudlak综合征（HPS）引起相当大的发病率和死亡率， 然而，了解引起综合征和有效性的基因的知识 治疗很少。 相反，在小鼠中的研究已经确定 至少14个直接引起HP的不同基因。 长期的 这项研究的目的是利用小鼠的遗传优势 克隆并表征小鼠HPS和相应的人类同源物 更好地了解原因，并最终设计严重的疗法 人类HP的形式。 特别是，提议克隆并部分地 表征了更明确的小鼠HPS基因之一Ruby Eye。 红宝石 眼基因具有内在的兴趣，不仅是因为它会引起HPS，还因为 因为它调节了三个的生物发生/加工/分泌 亚细胞细胞器；黑素体，溶酶体和血小板致密颗粒。 该提案的具体目的是：（1）识别小鼠红宝石眼 （RU）位置/候选基因方法的基因； （2）隔离人 对应于Ruby Eye cDNA的同源物，并在此中测试改变 HPS中的基因； （3）部分表征表达式和 小鼠红宝石眼基因的调节。