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P5-Mouse Phenotyping

P5-小鼠表型分析

基本信息

批准号：
7659502
负责人：
VAHRAM HAROUTUNIAN
金额：
$ 23.36万
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：
2008
资助国家：
美国
起止时间：
2008-07-16 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7659502
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 Gene Proteins Genes Genetic Glutamate Decarboxylase Glutamate Receptor Grant Haloperidol Homologous Gene Image 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 Numbers Oligodendroglia Parahippocampal Gyrus Peripheral Persons Pharmaceutical Preparations Phenotype Play Protein Overexpression 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 Thinking Time Transferrin Update Viral Oncogene Work base behavior influence behavior test brain tissue cingulate cortex genetic association in vivo interest laser capture microdissection mouse model myelination neurochemistry neuroimaging oligodendrocyte precursor phosphoric diester hydrolase postsynaptic density protein precursor cell prepulse inhibition protein expression putamen research study response stereotypy transcription factor white matter 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的小鼠模型系统