P5-Mouse Phenotyping

P5-小鼠表型分析

基本信息

批准号：
8479524
负责人：
VAHRAM HAROUTUNIAN
金额：
$ 7.44万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8479524
关键词：
Acoustics Acute Erythroblastic Leukemia Address Affect Age Age-Months Agonist Amphetamines Animal Model Animals Anisotropy Anterior Antipsychotic Agents Anxiety Apomorphine Autopsy Behavior Behavioral Biological Models Boxing Brain Brain region Cells Cellular biology Cognitive Collaborations Complex Consultations Corpus striatum structure Coupled Cyclic Nucleotides Development Dopamine Equilibrium Esthesia Ethylnitrosourea Etiology Evaluation Evolution Exposure to G-substrate GTP-Binding Proteins Gelsolin Gene Abnormality Gene Expression Genes Genetic Glutamate Decarboxylase Glutamate Receptor Grant Haloperidol Homologous Gene Image Indium-111 Individual Ketamine Knock-out Knockout Mice Learning Locomotion Memory Messenger RNA Modeling Modification Molecular Motor Motor Activity Mus Mutation Myelin Myelin Associated Glycoprotein Myelin Proteins N-Methyl-D-Aspartate Receptors Neuroanatomy Neurons Oligodendroglia Parahippocampal Gyrus Peripheral Persons Pharmaceutical Preparations Phenotype Play Proteins Reagent Receptor Signaling Reflex action Regulation Reporting Resources Rodent Model Role Schizophrenia Screening procedure Signal Transduction Social Interaction Specificity Specimen Staging Structure Superior temporal gyrus Synapses Synapsin I Techniques Testing Time Transferrin Update Viral Oncogene Work base behavior influence behavior test brain tissue cingulate cortex genetic association in vivo interest laser capture microdissection meetings molecular phenotype mouse model myelination neurochemistry neuroimaging oligodendrocyte precursor overexpression phosphoric diester hydrolase postsynaptic density protein precursor cell prepulse inhibition protein expression putamen research study response sex-determining region Y protein stereotypy transcription factor white matter working group young adult

项目摘要

This project is dedicated to the development and characterization of mouse model systems that best reflect the myelin and oligodendrocyte related (OMR) gene expression deficits in persons with schizophrenia. Several different genetically modified mouse model systems will be evaluated (e.g., Quaking, MAG, PTPRZ1, and Olig2. Each of these mouse model systems will be screened for deficits in the expression of OMR genes using a panel of OMR genes that we have shown to be differentially affected in schizophrenia. Those that evidence gene expression deficits on at least 3 OMR genes known to be affected in schizophrenia will then be assessed for behavioral deficits. The behavioral phenotyping test battery will include screening tests of simple (e.g., reflexes, locomotion, balance, sensation) as well as complex (learning, memory, startle, prepulse inhibition of startle, social interaction, anxiety) behaviors. Coupled with these purely behavioral tests will be pharmacological probes to ascertain whether pharmacological profiles commonly viewed as prototypical for rodent models of schizophrenia are also evidenced by the OMR gene deficient mice. Once "best-fit" model systems have been identified, they will be studied longitudinally to ascertain the evolution of gene expression and behavioral deficits from 3 months of age through to 18 months of age. In addition, laser capture microdissection techniques will be employed to investigate gene expression in identified cell groups. In collaboration with Project 1, the "best-fit" mouse model system will be systematically imaged by DTI in vivo at ages corresponding to those for behavioral testing. In collaboration with Project 3, brain tissue specimens from additional mice will be studied for changes in oligodendroglial proliferation, differentiation and survival. Significant progress has already been made in this regard. All of the behavioral test paradigms have been piloted and parameters have been optimized for use in mice in our phenotyping facility (results and descriptions appended). Three of the 4 animal model systems proposed for use (Quaking, Olig2, and MAG) have been obtained. Some studies have already been completed in these mice and colonies have been established to enable more large scale studies.

该项目致力于最能反映的鼠标模型系统的开发和表征精神分裂症患者的髓磷脂和少突胶质细胞（OMR）基因表达缺陷。将评估几种不同遗传修饰的小鼠模型系统（例如，Quaking，mag， ptprz1和olig2。这些鼠标模型系统中的每一个都将筛选在表达中的缺陷 OMR基因使用一系列OMR基因，我们证明在精神分裂症中受到差异影响。那些证明基因表达缺陷至少3个已知影响的OMR基因的缺陷然后，将评估精神分裂症的行为缺陷。行为表型测试电池将包括简单的筛选测试（例如反射，运动，平衡，感觉）以及复杂（学习，记忆，惊吓，对惊吓，社交互动，焦虑）行为的行为。加上这些纯粹的行为测试将是确定药理学特征的药理探针 OMR基因也证明了通常被视为精神分裂症啮齿动物模型的典型型不足的小鼠。一旦确定了“最佳拟合”模型系统，将纵向研究确定基因表达和行为缺陷从3个月到18岁的演变几个月。此外，将采用激光捕获微分解技术来研究基因在已识别的细胞组中的表达。与项目1合作，“最佳拟合”鼠标模型系统将是由DTI在体内成像的年龄与行为测试相对应的年龄。合作使用项目3，将研究其他小鼠的脑组织样品，以改变寡头的变化增殖，分化和生存。在这方面已经取得了重大进展。所有人行为测试范例已被试用，并且已经优化了参数以在我们的小鼠中使用表型设施（结果和描述附加）。提出的四个动物模型系统中的三个已经获得了使用（Quaking，Olig2和mag）。一些研究已经完成已经建立了小鼠和菌落以实现更多的大规模研究。