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Hearing loss in claudin 11-null mice

密蛋白 11 缺失小鼠的听力损失

基本信息

批准号：
7244263
负责人：
Alexander Gow
金额：
$ 22.8万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-15 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7244263
关键词：
Accounting Address Adult Affect Age Age-Months Auditory Auditory Brainstem Responses Basal Cell CLDN14 gene Cell membrane Cells Cochlea Cochlear duct Code Data Defect Depth Development Diffusion Disease Electron Microscopy Embryo Endolymph Exhibits Facility Construction Funding Category Family member Freeze Fracturing Frequencies Galactosidase Gap Junctions Genes Genetic Enhancer Element Goals Hair Cells Hand Hearing Heterogeneity Histology Immunohistochemistry In Situ Hybridization Individual Inner Hair Cells Knock-out Knockout Mice Knowledge Labyrinth Lead Measurement Measures Monitor Mus Mutant Strains Mice Northern Blotting Numbers Pathogenesis Pathology Perilymph Permeability Phenotype Potassium Process Production Property Recycling Reporter Reporter Genes Role Scanning Electron Microscopy Stria Vascularis System Testing Testis Tight Junctions Time Tracer Transgenes Transgenic Mice Transgenic Organisms Vestibular membrane Week Western Blotting beta-Galactosidase cell type claudin-1 protein day deafness embryonic stem cell fighting hearing impairment homologous recombination insight novel postnatal programs research study size solute stem transgene expression young adult

项目摘要

DESCRIPTION (provided by applicant): The long term goals of this project are to define the functions of tight junctions in Stria vascularis of the inner ear and to determine if the diversity of Claudin family members that comprise fight junctions located around Scala media have overlapping or non-overlapping properties. The knowledge gained from these studies will provide deep insights into the roles of the stria vascularis in hearing and potassium recycling to the endolymph. The specific aims are: 1) to test the hypothesis that inner ear pathology in Claudin//-null mice stems from morphological defects. Claudin 11 is expressed in the developing vestibulocochlear apparatus of embryos from E13.5 as well as in adults and evidence of gross structural changes during development and postnatally that could account for the pathology in the knockout mice will be sought. 2) to test the hypothesis that Claudin 11-null mice exhibit early hearing defects. Young adult knockout mice exhibit elevated auditory brainstem response (ABR) thresholds which indicate hearing loss, Further testing of ABRs as well as measurements of endocochlear potentials and DPOAEs at different ages will reveal if this phenotype is progressive or present at the time mice normally start to hear. 3) to optimize a transgene cassette for the expression of heterologous genes in basal cells of Stria vascularis. Basal cell-specific enhancer elements already in-hand will be located within the Claudin 11 gene and used to drive expression of a beta-galactosidase reporter gene in the cochlea, Reporter expression will be characterized with a view to expressing several claudin cDNAs in the cochlea in attempts to rescue hearing loss in Claudin 11-null mice.

描述(申请人提供)：这个项目的长期目标是确定内耳血管纹紧密连接的功能，并确定克劳丁家族成员的多样性是否包括位于中阶周围的战斗连接具有重叠或非重叠特性。从这些研究中获得的知识将为深入了解血管纹在听力和钾循环到内淋巴中的作用提供深入的见解。其具体目的是：1)验证Claudin//空小鼠内耳病理起源于形态缺陷的假说。Claudin 11在E13.5和成年胚胎发育中的前庭耳蜗器中表达，并将寻找在发育过程中和出生后大体结构变化的证据，这可能解释基因敲除小鼠的病理。2)验证Claudin 11基因缺失小鼠出现早期听力障碍的假设。年轻的成年基因敲除小鼠表现出听力损失的听性脑干反应(ABR)阈值升高，进一步的ABR测试以及不同年龄的耳蜗内电位和DPOAEs的测量将揭示这种表型在小鼠正常开始听力开始时是进行性的还是存在的。3)优化外源基因在血管纹基底细胞中表达的转化盒。已有的基本细胞特异性增强子元件将位于Claudin 11基因内，并用于驱动β-半乳糖苷酶报告基因在耳蜗中的表达，Reporter的表达将被鉴定，以期在耳蜗中表达几个claudin cDNA，试图挽救Claudin 11基因缺失小鼠的听力损失。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Increased anesthesia time using 2,2,2-tribromoethanol-chloral hydrate with low impact on mouse psychoacoustics.

DOI：
10.1016/j.jneumeth.2013.07.004
发表时间：
2013-09-30
期刊：
JOURNAL OF NEUROSCIENCE METHODS
影响因子：
3
作者：
Maheras, Kathleen J.;Gow, Alexander
通讯作者：
Gow, Alexander

Transgene-mediated rescue of spermatogenesis in Cldn11-null mice.

转基因介导的 Cldn11 缺失小鼠精子发生的拯救。

DOI：
10.1095/biolreprod.111.096230
发表时间：
2012
期刊：
Biology of reproduction
影响因子：
3.6
作者：
Wu,Xin;Peppi,Marcello;Vengalil,MatthewJ;Maheras,KathleenJ;Southwood,CherieM;Bradley,Michael;Gow,Alexander
通讯作者：
Gow,Alexander

Developmental window of sensorineural deafness in biotinidase-deficient mice.

生物素酶缺陷小鼠感音神经性耳聋的发育窗口。