Director Area Staff Consultants
Wallace Chick, PhD Genetic Engineering Kris Williams, BS
Michael Mesches, PhD Behavioral Testing Ops Nicolas Busquet, PhD Jerry Rudy, PhD
Natalie Serkova Imaging Kendra Hasebroock, BS
This core has four main objectives: (a) to provide animal genotyping services to IDDRC investigators; (b) to assist IDDRC investigators with the design and generation of new genetically modified mouse models of IDD; (c) to provide advice, assistance, and services for high-quality behavioral testing of mice and rats; and (d) to perform state-of-the-art non-invasive imaging (MRI, PET, CT) to assess IDD-related changes in rodent brain structure and function.
(Investigators: Please remember to acknowledge your Colorado IDDRC affiliation and your use of the cores in all your published papers. For an example of working to use, clock on the "For Investigators" tab.
VIDEO: Animal Models Core
The following services are provided through the Center of Neuroscience and the Cancer Cente, in cooperation with the CCTSI.
1. Transgenic/Knockout/Knockin Mouse Generation
Contact: Wallace Chick (email@example.com)
The engineering of genetically altered mice involves the production of an appropriate vector. This work is done by the Vector Construction Core The cell and animal work is done in cooperation with the Transgenic and Gene Targeting Core directed by P. Koch, PhD. The Colorado IDDRC Animal Models core breeds and maintains these mice. Please request consultation/service through the Core Management Tool.
Contact: Kris Williams (firstname.lastname@example.org).
Mouse genotyping can be done with traditional PCR or Real Time Quantitative PCR. Please see http://www.ucdenver.edu/TargetingVectorCore.
3. Behavioral Assessment.
Contact: Mike Mesches (Michael.Mesches@ucdenver.edu)
The Animal Models Core provides animal housing in close proximity to testing with identical light/dark cycles. Standard behavioral assays for mice and rats:
Cognition: Morris water maze, radial arm water maze, novel place and novel object recognition, Barnes maze, contextual fear conditioning, stimulus discrimination, instrumental conditioning, inhibitory avoidance, and conditioned taste aversion.
Altered emotionality: Elevated plus maze, light/dark discrimination, tail suspension, acoustic startle, and prepulse inhibition.
Motor function: Rotorod, open field, grip strength, and cat walk gait analysis.
Sensory tasks: Visual cliff test, tail flick, and foot shock assessment.
Task Development: The Animal Behavior Core staff are available to help develop or institute other behavioral tasks. Contact Dr. Busquet for further information.
IDDRC investigators with little experience in rodent behavioral analysis can consult with Drs. Mesches or Busquet to develop an experimental strategy (including test selection, protocol design and power analysis for proper selection of animal numbers).
Limited technical assistance for behavioral testing is available. Typically, Drs. Mesches or Busquet train technical personnel of the investigator’s laboratory in the performance of behavioral tests. Dr. Mesches also can facilitate contact with qualified part-time personnel to conduct the behavioral studies (at the investigator’s cost).
Interested researchers should contact Dr. Mesches or Dr. Busquet to schedule a consultation appointment. There is no consultation charge for IDDRC investigators.
VIDEO: Animal Behavior subcore
4. Small-Animal Radiologic Imaging
Contact Person: Natalie Serkova (Natalie.Serkova@ucdenver.edu)
MRI/CT/PET Services Website
Non-invasive imaging technologies allow for the assessment of anatomical as well as functional parameters in rodents and enable longitudinal studies of time-dependent effects in the same animal. Services aer provided to IDDRC investigators through the University of Colorado Cancer Center:
- Anatomic MRI: provides high-resolution brain images with superb soft tissue contrast. The spatial resolution is approximately 90 μm, which allows both visualization and volumetric measurements of various parts of the brain (as small as the pituitary gland - 4 mm3) without the use of ionizing radiation or contrast agents.
- Anatomic CT: provides high-resolution images (50 μm) of bone and soft-tissue structures (soft tissue resolution is poorer than that of MRI).
- Functional FDG-PET: Injection of radioactive 18fluorine-D-deoxyglucose (FDG) allows for assessment of brain activity during a 1-hour uptake period (no anesthesia required for the uptake period). Higher brain activity will correspond to higher intensity on FDG-PET scans. This is a novel and, to our knowledge, unique imaging application that is currently under development in the facility.
- Gadolinium-enhanced MRI: Clinically used gadolinium-based contrast agents (for MRI) are incapable of crossing the blood-brain barrier. Therefore, a disruption of the blood-brain barrier can be visualized using gadolinium-enhanced MRI.
- Diffusion-weighted MRI: allows for assessment of brain edema and brain necrosis based on diffusion coefficients (ADC mapping) for tissue water.
- In-Vivo 1H-MRS: allows (after localized MRI) to determine non-invasively major brain endogenous metabolites, such as the MR neuronal marker N-acetyl-aspartate, glial marker myo-inositol, neurotransmitters GABA and glutamate, as well as total choline (membrane biosynthesis) and total creatine (energy metabolism). Additional, expanded (ex vivo) metabolic profiling can then be achieved by high-resolution NMR after tissue sampling (see below).
- Molecular Imaging: Using novel radiolabeled or MR relaxing reporters (for PET and MRI, respectively) attached to a specific compound (e.g., metabolic substrate/precursor), it is possible to visualize molecular targets (such as certain proteins or metabolic activity) in vivo.
VIDEO: Small Animal Imaging