Mouse Applications

Overview:

The House Mouse (Mus musculus) is a small mammal and a rodent. Laboratory mice are strains of House Mice that are hybrids of different subspecies, most commonly of Mus musculus domesticus and Mus musculus musculus. They can have a variety of coat colours including agouti, black and albino (white).

Laboratory mice are:

  • A primary mammalian model organism like rats
  • The most commonly used animal research model
  • Some of the most important model organisms in biology, psychology and medical research
  • Available in hundreds of established inbred, outbred and transgenic strains

The benefits of using mice in laboratory research include:

  • They are mammals, and thus share a high degree of homology with humans
  • The mouse genome has been sequenced and virtually all mouse genes have human homologs
  • The mouse genome can be easily manipulated in many ways
  • Mice can reproduce quickly
  • Several generations of mice can be observed in a relatively short period of time
  • Mice are small, inexpensive and easily maintained
  • Some mice can become docile if raised from birth and given sufficient human contact

Method:

Biopotential Recordings

Measurements of biopotentials such as ECG, EMG and EEG in mice can be made using the Animal Bio Amp, which is specifically configured for this application. In addition, other ADInstruments bio amplifiers certified safe for humans may also be used on mice. Multi-Channel Bio Amps are also available for recording three or more biopotentials from a single subject. ADInstruments also provide a range of lead wires and electrodes for use with these bio amplifiers including Needle and Spring Clip Electrodes.

Non-Invasive Blood Pressure (NIBP)

ADInstruments provides a NIBP System for the measurement of blood pressure in conscious mice. It consists of a pulse transducer and inflatable tail pressure cuff specifically configured for use with mice (tail diameters ≤ 6mm). This system integrates with any PowerLab data acquisition system and records both the cuff pressure and pulse transducer signal from the tail artery.

The NIBP system occludes the tail blood supply by inflating the cuff while the pressure is slowly released. A sensitive pulse transducer then detects the return of blood flow in the tail. This system provides an intermittent determination of systolic blood pressure (once per cuff inflation cycle) the same way as a human arm cuff determination. ADInstruments also provides appropriate Rodent Restrainers for use with mice.

Intra-Arterial Blood Pressure and Cardiac Catheterization

An accurate method for measuring blood pressure in small animals is through the use of indwelling catheters and pressure sensing transducers. ADInstruments supply a number of blood pressure transducers that are connected to any PowerLab data acquisition system via an ADInstruments Bridge Amp.

In vivo catheterization of the left ventricle in the closed-chest mouse is also a common technique used for evaluating cardiac performance. Due to the small size and frequency-response in mouse hearts ADInstruments offer a range of Mikro-Tip Catheters (by Millar Instruments) which integrate easily with any ADInstruments Bridge Amps and PowerLab data acquisition system. The SPR-1000 Mikro-Tip Catheter is recommended for in vivo catherization in mice because it is an ultra miniature (1.0F, 0.33mm), highly accurate, reusable pressure catheter that provides greater flexibility with minimal obstruction of vessels or valves. ADInstruments also offers Millar Pressure-Volume Systems (MPVS) configured for measuring pressure and volume in the left ventricle to determine of cardiac function in mice.

Blood Flow

Laser Doppler systems may be used to measure blood flow in mice. This method is ideal for use in the mouse as the method detects changes in the smallest of blood vessels, where most other techniques are of little use. For example surface probes can sit on the brain for cerebral perfusion measurements, or needle probes can be inserted for the determination of blood flow in specific organs/tissues.

Other applications include:

  • Evaluation of vasoactive drugs on microcirculation
  • Monitoring of peripheral circulation
  • Monitoring of exposed animal tissue microcirculation

Transit-time ultrasound systems (by Transonic Systems) can also provide continuous measurements of blood flow in mice. An indwelling probe can be positioned around the aorta or pulmonary artery for direct determination of flow rate. Flow probes incorporate two transmitters/sensors and a reflector plate that allow them to provide calibrated measurements of blood flow in milliliters per minute.

Cardiac Output

Cardiac output in mice can be measured using the thermodilution method. This method involves the injection of a cooled bolus solution (usually saline) of a known volume and temperature into the right side of the heart and measuring the change in temperature within the circulation. The resultant temperature change in the blood ejected from the heart is measured with a temperature probe placed in the aorta or carotid artery. A curve showing acute blood temperature change is plotted over time and the area under the curve is calculated. Cardiac output is inversely related to this: a small area under the curve indicates more rapid blood flow, while a large area will indicate more gradual changes in temperature as a result of lower cardiac output.

Isolated Heart Preparation

The mouse heart can also be studied ex vivo using isolated heart preparations. This is ideal for assessing cardiac performance to drugs or ischaemic conditions, in the absence of autonomic nervous system tone, or effects of anaesthesia. The heart is maintained at constant temperature and heart function is sustained through coronary system perfusion with oxygenated physiological buffer. Cardiac parameters measured include LVP, Max and Min dP/dt, LVEDP, cardiac electrical activity, heart rate, coronary perfusion pressure and many others.

There are many models of isolated heart preparations including:

  • Langendorff and Working Heart
  • Constant pressure and Constant flow
  • Recirculating and non-recirculating

Additional information is available in the Radnoti Isolated Perfused Heart (255 KB) and Intraventricular Pressure Measurement in a Langendorff Preparation (92 KB) technique notes.

Isolated Tissue and Microvascular Function

Mice are also used in organ bath studies of smooth muscle function including small arteries, veins and other tubular tissues, such as the bronchus and the ureter. Vessel Myograph Systems, such as those by Danish Myo Technology (DMT), can be used to record tension in microvessels (> 60 µm). Modular tissue-organ baths by Radnoti Glass Technology and compact all-in-one design Organ Baths by Panlab are also available as complete research systems.

Wireless Recording

Analog adapters for interfacing PowerLab systems with a range of Data Sciences International, DSI Telemetry Transmitters for mice are also available and allow data acquisition and analysis in LabChart.

Software:

The LabChart Advantage:

(may require additional Modules and Extensions)

  • LabChart data files can be marked with events using the Comments feature
  • The Units Conversion feature can be used to convert signals into relevant units e.g. mmgH, ml/min, mN, etc.
  • Software anlysis modules for automated detection and extraction of parameters of interest including ECG, HRV, BP, PV Loop Analysis, Cardiac Output, Dose Response and DMT Normalization
  • Macros can automate many tedious and repetitive analysis tasks
  • Data can be easily transferred into popular spreadsheet and graphing programs for further analysis and reporting

LabChart

LabChart software (for Windows and Macintosh) together with a PowerLab data acquisition system offers up to 32 channels of real-time data acquisition, data integrity, easy selection of hardware settings, powerful online and offline analysis, procedure automation, seamless extraction of experimental data and flexible display options. Additional acquisition and analysis functionality is provided with the use of specialized LabChart Extensions and LabChart Modules. Modules are available as part of LabChart Pro while Extensions are free for download from the website for existing LabChart users.

ECG Analysis Module
The ECG Analysis Module (Windows) provides a comprehensive set of tools that automatically detects and reports values of ECG recordings. The software can be used with ECG recordings taken from humans and many species of animals from pigs through to mice.

It provides

  • Real-time analysis and data extraction of ECG parameters
    • PQRST amplitudes
    • Time intervals such as RR, PR, JT, QT and QTc
  • Analysis of ECG parameters in real-time or offline
  • Automated detection and averaging of ECG cycles
  • Automated tabulation and data extraction of ECG parameters
  • Automated real-time or offline ECG Plots
    • Graphical QT vs RR, QT vs Time & RR vs Time plots
    • Waterfall plot

Blood Pressure Module
The Blood Pressure Module (Windows) automatically detects, analyzes and reports cardiovascular parameters from arterial or ventricular pressure signals.

It provides:

  • Real-time analysis and data extraction of pressure parameters
    • Max and min pressures
    • Max and min dP/dt
  • Analysis of blood and cardiac pressure in real-time or offline
  • Automated detection of pressure cycles
  • Automated tabulation and data extraction of pressure parameters
  • Analysis View
    • Averaging of pressure waveforms
    • Automated pressure parameter labeling

Cardiac Output Module
The Cardiac Output Module (Windows) provides easy extraction and calculation of cardiac output from small animals recorded in LabChart, using the thermodilution technique.

It provides:

  • Automatic calculation of cardiac output in mL/min from a thermodilution curve
  • Automatic calculation of baseline temperature and baseline slope correction
  • Automatic calculation of the area under the curve
  • Automated extraction of exportable parameters in a spreadsheet format

Dose Response Module
The Dose Response Module (Windows) provides easy analysis of dose response type data (response to stimulation by chemical, electrical or physical agonists) recorded in LabChart from various studies including:

  • Muscle contraction
  • Enzyme activity
  • Hormone secretion
  • Heart rate
  • Blood pressure
  • Membrane potential

It provides:

  • Real-time or offline analysis
  • Automated or manual modes of analysis
  • Fast analysis of raw data to dose response parameters
    • Fast comment detection and conversion to dose response markers
    • Easy options for calculating different response parameters
    • Instant single or multiple dose response curves (Hill-curves) generation
    • Instant calculation of EC50 and Hill slopes  
  • Export options to other software applications for further analysis

Peak Analysis Module
The Peak Analysis Module (Windows) provides automatic detection and analysis of multiple, but not overlapping, signal peaks in acquired waveforms. It can be applied to a wide range of waveforms including recorded signals from:

  • Isolated tissue studies
  • Hemodynamic measurements
  • Amperometry
  • Cardiac physiology
  • Neurophysiology
  • Current measurements.

It provides:

  • Real-time or offline analysis
  • Fast parameter extraction and analysis from single or multiple peaks
  • Automatic peak detection of an entire channel or a selection within a channel
  • Detection of positive or negative peaks
  • Several analysis presets suitable for general and specific types of waveforms
    • Evoked Response, Population Spike, Synaptic, Action Potential and Cardiac Action Potential
  • Instant tabulation of extracted parameters that can be exported to other applications
    • Height, width, area of the peak and time to peak

DMT Normalization Module
The DMT Normalization Module (Windows and Macintosh) is designed for use with PowerLab data acquisition units, LabChart software and DMT Wire Myographs, and calculates the optimal pretension conditions for microvascular or any small tubular tissue research.

It provides:

  • Allows real-time and offline data recording and analysis
    • Tension
    • Stimulation amplitude
    • Temperature
    • Flow
  • Easy method of determining optimal microvascular pretension when using DMT myographs

PV Loop Module
The PV Loop Module (Windows) records and analyzes left ventricular pressure and volume data for hemodynamic research in animals. Analyses can be conducted during or after sampling.

It features:

  • Loop View- plots and displays the key cardiac parameters and allows individual loops to be reviewed and selected for inclusion/exclusion in analyses. Parameters include;
    • ESPVR (End Systolic Pressure-Volume Relationship). The slope of the ESPVR curve is an index of myocardial contractility; the steeper the ESPVR curve, the greater the cardiac contractility.
    • EDPVR (End Diastolic Pressure-Volume Relationship). The slope of the EDPVR curve is an indicator of ventricular compliance; the steeper the curve, the greater the ventricular stiffness.
  • Hemodynamics Table- reports parameters for each individual loop including:
    • Stroke Work
    • Cardiac Output
    • Ejection Fraction
    • Tau (the Isovolumic Relaxation Constant)
  • Analysis Plots
    • PRSW View (Preload-Recruitable Stroke Work) is used as an index of contractility
    • dP/dt Max vs. EDV View shows the steepest slope during the upstroke of the pressure curve versus end diastolic volume and is used as an index of contractility
    • PVA vs. EDV Plot (PVA is the mechanical energy generated by contraction of the ventricle)
    • PVA vs. ESP Plot
  • Automated Calibration
    • Cuvette calibration - for calculating absolute volume units using calibration curettes
    • Saline calibration - for determining parallel conductance of ventricular wall (Vp)

GLP and 21 CFR Part 11
For those researchers working within a laboratory requiring GLP and 21 CFR Part 11 compliance, the GLP Client and GLP Server are available for use with LabChart (Windows only) and PowerLab data acquisition systems. For more information, visit the Good Laboratory Practice application page or contact your nearest ADInstruments representative.

Hardware:

PowerLab Data Acquisition Systems

The PowerLab is a high-performance data acquisition unit capable of recording at speeds of up to 400,000 samples per second continuously to disk (aggregate). PowerLab units are compatible with instruments, signal conditioners and transducers supplied by ADInstruments, as well as many other third-party companies. In addition to standard single-ended BNC inputs, 4 differential Pod ports are also available for direct connection of Pod signal conditioners and appropriate transducers. Research PowerLab units include:

Research Systems

Mikro-Tip Blood Pressure and Pressure-Volume Systems

Transit-Time Ultrasound Blood/Fluid Flow Systems

Isolated Perfused Heart Preparation

Small Vessel and Muscle Myography

Isolated Tissue-Organ Bath

Signal Conditioners

Biopotential Recording

Intra-Arterial Blood Pressure

Cardiac Output (Thermodilution)

Instruments

Non-Invasive Blood Pressure (NIBP) System

Laser Doppler Blood Flow

Transducers and Accessories

Biopotential Electrodes for ML136 Animal Bio Amp

Fluid-filled Blood Pressure Transducers

  • MLT844 Physiological Pressure Transducer: Suitable for pressures ranging from -20 to +300 mmHg. Includes disposable clip-on domes and a 4 pin to 8 pin DIN cable to connect to any Bridge Amplifier.
  • Ideal for monitoring MAP during anaesthesia. Not recommended for blood pressure analysis studies.
  • MLA1052 Pressure Gauge and accessories for calibrating fluid-filled or Millar Mikro-Tip pressure transducers

Mikro-Tip Pressure Catheters

Mikro-Tip Pressure- Volume Catheters

Millar Mikro-Tip Catheter Interface Cables

Cardiac Output

NIBP Mouse Restrainers

Laser Doppler Probes

Analog Adapters for DSI Transmitters (single-channel)

GLP and 21 CFR Part 11
For those researchers working within a laboratory requiring GLP and 21 CFR Part 11 compliance, the GLP Client and GLP Server are available for use with LabChart (Windows only) and PowerLab data acquisition systems. For more information, visit the Good Laboratory Practice application page or contact your nearest ADInstruments representative. 

A practical guide to evaluating cardiovascular, renal, and pulmonary function in mice
J N Lorenz, American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, R1565-R1582, 2002

Renal blood flow and dynamic autoregulation in conscious mice
Iliescu R, Cazan R, McLemore G R Jr, Venegas-Pont M, Ryan M J, American Journal of Physiology: Renal Physiology, F734–F740, 2008

FAK regulates cardiomyocyte survival following ischemia/reperfusion
Hakim Z S, DiMichele L A, Rojas M, Meredith D, Mack C P, Taylor J M, Journal of Molecular and Cellular Cardiology, 241–248, 2009

The effect of prepregnancy obesity and sFlt-1–induced preeclampsia-like syndrome on fetal programming of adult vascular function in a mouse model
Byers B D, Betancourt A, Lu F, Hankins G D V, Longo M, Saade G R, Bytautiene E, American Journal of Obstetrics and Gynecology, 432e1-432e2, 2009

Citations Database


The material on this page is provided in good faith and believed accurate at the time of writing. No responsibility will be taken, or liability accepted, for damages arising from the use of information herein. Readers are urged to check with respective manufacturers the accuracy of all product related information.

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