权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Modeling Fragile X Syndrome in Drosophila

果蝇脆性 X 综合征建模

基本信息

批准号：
7231962
负责人：
THOMAS A JONGENS
金额：
$ 31.28万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-15 至 2008-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7231962
关键词：
Adult Affect Anxiety Attention Behavior Behavioral Behavioral Model Behavioral Symptoms Biochemical Circadian Rhythms Cognitive Courtship Defect Dendrites Dendritic Spines Development Developmental Process Disease Down-Regulation Drosophila genus Drug effect disorder Excitatory Amino Acid Antagonists FMR1 FMR1 Gene Female Fragile Site Mental Retardation 2 Gene Fragile X Mental Retardation Protein Fragile X Syndrome Genes Genetic Growth Hippocampus (Brain)Homologous Gene Human Hyperactive behavior Immediate Recalls Incidence Inherited Lead Link Long-Term Depression Memory Mental Retardation Messenger RNA Metabotropic Glutamate Receptors Modeling Molecular Moods Morphology N-Methyl-D-Aspartate Receptors Neurons Pathway interactions Patients Pattern Pharmacological Treatment Phenotype Physiological Property Proteins RNA Binding RNA-Binding Proteins Range Rate Research Personnel Role Route Short-Term Memory Sleep Disorders Symptoms Therapeutic Ursidae Family Visual Cortex base dFMR1 gene density gene function loss of function male mouse model mutant neuronal growth prevent programs protein expression receptor response synaptic function

项目摘要

DESCRIPTION (provided by applicant): Fragile X syndrome is one of the most commonly inherited forms of human mental retardation with an incidence rate of 1 in 4000 males and 1 in 6000 females. It is caused by the loss of FMR1 gene function. Patients with Fragile X syndrome suffer from a variety of symptoms including; mental retardation, attention deficit, hyperactivity, sleep disorders, anxiety, unstable mood and autistic-like behaviors. Physical defects include macroorchidism and irregular dendritic spine morphology. In previous studies, our lab developed a Fragile X model in Drosophila. This model is based on the dfmr1 (also called dfxr) gene, which has a high degree of sequence identity/similarity to the FMR1 gene. The dFMR1 protein has similar RNA binding properties, developmental expression pattern and subcellular distribution to the FMR1 protein (FMRP). In recent studies, we have shown that dfmr1 null mutants display several behavioral defects that bear similarity to symptoms of Fragile X patients. The relevant phenotypes in Drosophila include arrhythmic circadian behavior, attention deficit during courtship, memory defects and subtle defects of neuronal morphology. The similarities in the biochemical properties of dFMR1 and FMRP and their loss of function phenotypes suggest that these two proteins have conserved function in similar behavioral and developmental processes. Thus the Drosophila dfmr1 mutants are a relevant model to study aspects of Fragile X syndrome. To ameliorate Fragile X syndrome it is imperative that we understand when and how FMR1 activity functions to prevent cognitive and behavioral defects. The temporal requirements and molecular role of FMR1 are currently not known. We propose to use the Drosophila model of Fragile X to determine when dfmr1 activity is required to determine if the behavioral defects are due to developmental or physiological defects. We are also investigating possible physiological pathways affected by loss of dfmr1 function. Through these studies we have identified a pharmacological treatment that rescues the courtship and memory defects displayed in our dfmr1 mutants. In this proposal we will determine and verify a route of action of this drug to identify potential targets for the treatment of Fragile X syndrome.

描述（由申请人提供）：

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability.

DOI：
10.1038/ncb1872
发表时间：
2009-05
期刊：
NATURE CELL BIOLOGY
影响因子：
21.3
作者：
Kirino, Yohei;Kim, Namwoo;de Planell-Saguer, Mariangels;Khandros, Eugene;Chiorean, Stephanie;Klein, Peter S.;Rigoutsos, Isidore;Jongens, Thomas A.;Mourelatos, Zissimos
通讯作者：
Mourelatos, Zissimos

Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment.

DOI：
10.1016/j.brainres.2010.11.032
发表时间：
2011-03-22
期刊：
Brain research
影响因子：
2.9
作者：
Choi CH;Schoenfeld BP;Bell AJ;Hinchey P;Kollaros M;Gertner MJ;Woo NH;Tranfaglia MR;Bear MF;Zukin RS;McDonald TV;Jongens TA;McBride SM
通讯作者：
McBride SM

Age-dependent cognitive impairment in a Drosophila fragile X model and its pharmacological rescue.

DOI：
10.1007/s10522-009-9259-6
发表时间：
2010-06
期刊：
BIOGERONTOLOGY
影响因子：
4.5
作者：
Choi, Catherine H.;McBride, Sean M. J.;Schoenfeld, Brian P.;Liebelt, David A.;Ferreiro, David;Ferrick, Neal J.;Hinchey, Paul;Kollaros, Maria;Rudominer, Rebecca L.;Terlizzi, Allison M.;Koenigsberg, Eric;Wang, Yan;Sumida, Ai;Nguyen, Hanh T.;Bell, Aaron J.;McDonald, Thomas V.;Jongens, Thomas A.
通讯作者：
Jongens, Thomas A.

Argonaute2 suppresses Drosophila fragile X expression preventing neurogenesis and oogenesis defects.