MOLECULAR BASIS OF INHERITED DEAFNESS
遗传性耳聋的分子基础
基本信息
- 批准号:2393497
- 负责人:
- 金额:$ 19.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1994
- 资助国家:美国
- 起止时间:1994-07-01 至 2002-06-30
- 项目状态:已结题
- 来源:
- 关键词:angiogenesis inhibitors animal genetic material tag antisense nucleic acid clinical research complementary DNA congenital deafness ear hair cell enzyme activity enzyme induction /repression gene expression gene mutation human genetic material tag human subject isozymes laboratory mouse male myosins protein structure function sex linked trait tissue /cell culture
项目摘要
In this proposal we outline studies on three genes for inherited
deafness: those encoding Norrie (Norrie disease), myosin-VIIa
(Usher 1B and the shaker-1 mouse), and myosin-VIIb (a candidate
for the twirler and shaker-2 mouse mutants). The Norrie studies
continue work done in the first two years of t his grant, while the
myosin studies initiate two new programs.
Norrie disease is a rare X-linked syndromic deafness, with
congenital blindness and progressive hearing loss. We have
cloned the gene defective in this disease; it encodes a small,
secreted protein (norrin) that my be a growth factor. The
pathology in some vagrants of the disease suggest that a defective
norrin allows excessive growth of blood vessels - that it isnorally
an angiogenesis inhibitor. We propose several methods to test this
hypothesis, and propose to initiate or continue audiometric and
histological studies of both humans and mice with this defective
gene.
Usher 1B presents with congenial deafness and absence of
vestibular function, and progressive loss of vision. It is the most
common genetic deafness in humans. The gene defective encodes
myosinVIIa, a protein that connects and moves other proteins on
action. We have closed human myosin-VIIa, and have used
antibodies to locate it in auditory receptor cells with electron
microscopy. We will test a specific hypotheses that myosin-VIIA
is involved in maintaining cohesion of the mechanosensitive cilia,
by using a mutant mouse, shaker-1, that has defective myosin-VIIa
and by using gene transfers to disrupt myosin-VIIa in normal
mice.
There is evidence that other myosin-VII isoforms exist in the
cochlea, and that they may also cause deafness when defective.
We have closed fragments of the genes and have compared their
chromosomal location to genetic deafness in mice. We propose to
clone these other isoforms, and to test them as candidate deafness
genes.
在本提案中,我们概述了三种遗传基因的研究
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
DAVID P COREY其他文献
DAVID P COREY的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('DAVID P COREY', 18)}}的其他基金
Development of Gene Therapy for Hereditary Deafness using Rational Protein Engineering
利用合理蛋白质工程开发遗传性耳聋基因疗法
- 批准号:
10649587 - 财政年份:2022
- 资助金额:
$ 19.2万 - 项目类别: