The Animal Physiology Core provides technically advanced physiological evaluation of metabolism in diabetes, obesity, and the associated complications in rodents for Joslin Diabetes Research Center investigators and outside users. These studies provide a critical platform for extension of molecular discoveries to in vivo settings that provide critical insights for relevance to human metabolic diseases. In addition, the Core provides hands-on training of investigators and trainees in several physiological procedures. This core collaborates with almost all of the other cores in the distribution of biofluids and tissues for genetic, genomic, and biostatistical analyses.
Comprehensive Laboratory Animal Monitoring System (CLAMS)
The Comprehensive Laboratory Animal Monitoring System from Columbus Instruments allows for simultaneous measurement of numerous parameters including oxygen consumption (VO2), carbon dioxide (CO2) production, respiratory exchange ratio (RER), food and drinking behavior, activity level, and caloric heat production. Measurements are done in the dark and light cycles, fed and fasted states, and can be used with special diets such as high-fat feeding. The CLAMS system has 12 chambers and utilizes a gas exchange sensor to monitor VO2 and VCO2. Data is analyzed through the Columbus Instruments CLAX 2.3 software for the preparation of graphs or can be exported to SigmaStat or Excel.
Sable Promethion System
Joslin recently purchased a Sable Systems Promethion Core High-Definition Metabolic Phenotyping System for metabolic studies in mice. The system accommodates 16 mice housed in home caging and allows for measurement of energy expenditure, oxygen consumption, CO2 production, VO2peak during exercise, respiratory exchange ratio (RER), heat generation calculated from gas exchange data, food consumption, water consumption, locomotor activity evaluated by three-dimensional fixed-point beam break observation, and voluntary wheel activity. The environmental sensor array captures 6 different parameters at once: humidity, barometric pressure, temperature, light, motion, and sound. The Stable Isotope Gas Analyzer continuously measures 13C and 18O isotopes in exhaled breath and allows the study of whole-body oxidation of endogenous and exogenous nutrients. The Promethion data analysis software package, ExpeData, allows the user to explore acquired data where each parameter of the system has been recorded once per second, enabling real-time analysis or for comparison to previous research.
The Dual Energy X-ray Absorptiometry instrument uses X-ray to assess lean and fat mass distribution, bone mineral density and bone length. Body composition by the DXA scanner can be performed on mice and rats up to 55 grams in weight. Analysis of the body scan is performed on defined regions of interest as indicated by the researcher. Total body, interscapular, abdominal, visceral and subcutaneous compartments can be measured for fat and lean mass. Length of major bones, including spinal cord, tibia and femur, can be measured using calibrated calipers
The Core maintains 3, 5-lane treadmills that accommodate both mice and rats and can be used for both training and acute exercise studies and 58 cage systems with running wheels that allow for mice and rats to voluntarily exercise. Treadmills can be connected to the CLAMS system to test maximum oxygen consumption, along with data for carbon dioxide production, respiratory exchange ratio, and caloric heat production. In addition, a Columbus Instruments Grip Strength Meter allows researchers to examine the strength of mice and rats in vivo.
A non-invasive tail-cuff sensor and monitoring system is used for the measurement of systolic and diastolic blood pressure and heart rate. Mice are measured with a system from Visitech Systems (BP-2000a), which can accommodate four mice for simultaneous measurement. Rats can be measured with the Visitech System that has an adapter allowing the conversion of the mouse system to a rat system, or a system from Ueda Electronics (UR-5000).
The PeriScan PIM3 System is a laser doppler based device that measures tissue vascular perfusion. Mice or rats can be measured with this system. Tissue blood flow is displayed as changes in the laser doppler frequency by a color scale. The system exports data in Excel or as a Word report with images.
Two Caron Diurnal Incubators (Model 6022-2) allow for more than one temperature study to be run simultaneously. These incubators have the ability to house animal cages from 5 degrees Celsius up to 30 degrees Celsius. The light cycles can also be adjusted on these incubators for studies using the 12 hour light/dark cycle or studies wishing to examine other variations of light/dark cycles.
An IVIS Spectrum micro CT imaging system (Caliper/Perkin Elmer) uses novel optical imaging technology to facilitate non-invasive longitudinal monitoring of disease progression, cell trafficking and regulated gene expression patterns in living animals via bioluminescent and/or fluorescent reporters. In addition, microCT generated 3D tomography can be measured simultaneously for anatomical context.
The OxyCycler System (BioSpherix Systems) allows users to investigate the effects of hypoxia and/or hyperoxia. This in vivo system, which can be used for mice or rats, consists of four sealed and independently controlled chambers in which oxygen concentration can be manipulated between 0.1% to 100%.
The dedicated gnotobiotic mouse facility supports microbiome studies at Joslin and the greater Harvard Medical School community. The facility supports the breeding and maintenance of mice in a completely sterile environment or allow for the selective colonization of a single microbe or a fully characterized microbial consortium. The Gnotobiotic Mouse Facility has four large breeding isolators that can house up to four mouse lines, as well as 12 smaller experimental isolators that can readily host up to six independent experiments at capacity. The isolators are HEPA-filtered, positive pressure vinyl bubbles purchased from and maintained by Class Biologically Clean, Ltd. that can house up to ten cages in each breeding isolator and five cages in each experimental isolator.
The Core provides training and equipment for anesthesia and metabolic testing. E-Z Anesthesia Isoflurane machines are available to anesthetize mice and rats for surgeries. These machines come equipped with a prep chamber to anesthetize the mouse or rat and the animal can then be moved to a nose cone to allow researchers to easily perform surgeries while the mouse is anesthetized. Core personnel also provide training on the performance of glucose tolerance tests (GTT) and insulin tolerance tests (ITT) and on the design of experiments using chemically-induced diabetes.
Remember to cite the DRC
If any of your research in publications has been supported in full or in part by our Core, please acknowledge our NIH/NIDDK grant as follows: "Supported by the Animal Physiology Core of NIH P30 DK036836."
For information regarding services and scheduling or to learn about the import option, email research assistant Meghan.Halpin [at] joslin.harvard.edu (Meghan Halpin).