P5-Mouse Phenotyping

P5-小鼠表型分析

基本信息

批准号：
8080387
负责人：
VAHRAM HAROUTUNIAN
金额：
$ 23.25万
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：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8080387
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 ERBB2 gene Equilibrium Esthesia Ethylnitrosourea Etiology Evaluation Evolution Exposure to G-substrate GTP-Binding Proteins Gelsolin Gene Abnormality Gene Expression Gene Proteins 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 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.

该项目致力于开发和表征最能反映精神分裂症患者的髓磷脂和少突胶质细胞相关（OMR）基因表达缺陷。将评估几种不同的转基因小鼠模型系统（例如，Quaking、MAG、 PTPRZ1 和 Olig2。将筛选每个小鼠模型系统的表达缺陷 OMR 基因使用一组 OMR 基因，我们已证明这些基因在精神分裂症中受到不同程度的影响。那些证明至少 3 个已知受影响的 OMR 基因存在基因表达缺陷的基因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（例如反射、运动、平衡、感觉）和复杂的筛选测试（学习、记忆、惊吓、惊吓的前脉冲抑制、社交互动、焦虑）行为。加上这些纯粹的行为测试将是药理学探针，以确定药理学特征是否 OMR 基因也证明了通常被视为精神分裂症啮齿动物模型的原型缺乏的老鼠。一旦确定了“最适合”的模型系统，将对它们进行纵向研究，以确定从 3 个月大到 18 岁的基因表达和行为缺陷的演变月龄。此外，激光捕获显微切割技术将用于研究基因在确定的细胞群中表达。与项目 1 合作，“最适合”的小鼠模型系统将在与行为测试年龄相对应的年龄通过 DTI 进行体内系统成像。合作中在项目 3 中，将研究来自其他小鼠的脑组织标本中少突胶质细胞的变化增殖、分化和存活。在这方面已经取得了重大进展。所有的行为测试范式已经进行了试点，参数也已经过优化，可用于我们的小鼠表型分析设施（结果和说明附后）。提议的 4 个动物模型系统中的 3 个已获得使用（Quaking、Olig2 和 MAG）。这些方面的一些研究已经完成小鼠和群体的建立是为了进行更大规模的研究。