AllresearchprojectsofthisProgramProject(PP)willrelyontheuseofgeneticallyengineeredmouse(GEM) modelstoinvestigatetherolesandmechanismofNuclearReceptors,transcriptionfactorsandtheircoregulators inenergyandmetabolichomeostasisanddisease.Morespecifically,atleast34GEMmouselineswillbeused, andthousandsofmaleandfemalemicewillbeproducedbybreedinginhouseduringthefundingperiodofthis PP.Therefore,thisAnimalComponentofCoreBisessentialforthesuccessofthisPPbyintegratingexpensive equipment, advanced technology, experienced personnel and animal resources. As shown by preliminary studies,CoreBhasgenerated/establishedmultipleGEMlinesanddevelopedCRISPR-Cas9-mediatedmouse geneeditingsystems.CoreBisdedicatedtoachieving3majorobjectives.Firstly,CoreBwilluseitsspecialized expertise, state-of-the-art equipment and adequate facilities to generate GEM lines for all investigators of this PP.CoreBhasestablishedthenecessarymethodstoeditthemousegenomebyhomologousrecombination- based gene targeting in ES cells or CRISPR/Cas9-based gene editing in 1-cell mouse embryos. Core B will generateallGEMlinesneededbytheinvestigatorsofthisPP.Secondly,CoreBwillprovidehighqualitymouse services to manage GEM line colonies and produce genotype-defined and age/sex-matched mice for all investigatorsofthisPP.Specifically,CoreBwillbreedandmaintainallofthe34mouselinesusedbythisPP. CoreBwilluseourcolonyexpansionprotocoltoproducelargenumbersofgenotype/age/sex-matchedmicefor experimental analysis. Core B also will perform genotype analysis, super ovulation, embryo and sperm cryopreservation,andinvitrofertilizationservicestohelptheinvestigatorsofthisPPformanagingtheirmouse colonies, preserving GEM lines, transferring mouse lines between institutes, and saving animal husbandry expenses. Finally, Core B will integrate the efficient usage of animal resources by all investigators of this PP. Becauseofthelarge-scaleoperationofmousemodelsandthesharingfeaturesofmultiplemouselinesamong the projects of this PP, centralized integration of equipment, expertise and valuable mouse resource will be essential for both scientific success and cost effectiveness. Core B will minimize the expenses of animal experiments by consolidating the usage and management of equipment, expertise, animal facility, mouse maintenanceandproduction.Inaddition,CoreBwillserveasaresourceforexecutionandtechnicaltrainingin theuseofallanimalmanipulationsneededandoverseethecareanduseofexperimentalmiceforthisPP.
Core B (Animal Component) - Project Narrative Because the pathways and mechanisms for maintaining energy and metabolic homeostasis are similar between human and mouse, the investigators of this Program Project will extensively use genetically engineered mouse (GEM) models to understand the roles of several crucial gene regulators in metabolic homeostasis and determine their therapeutic value in treating metabolic diseases. This Animal Component of Core B will provide comprehensive mouse services to support the success of this Program Project application.
