In Vivo Phenotyping
The phenotyping services at Harwell offer the opportunity for detailed characterisation of mouse lines.
The phenotyping service at Harwell offers a wide-range of both conventional and progressive phenotyping tests aimed at generating reproducible and robust data analysing a broad range of physiological systems.
All tests have validated standard operating procedures and undergo rigorous quality control as part of our ISO9001 accreditation. To ensure consistency in health status and breeding conditions, it is a prerequisite that all lines are embryonic rederived into the Mary Lyon Centre and that subsequent cohorts are bred to enable randomisation and blinding.
With an increasing emphasis on automation, MRC Harwell is striving to develop new phenotyping tests, extend the range and complexity of tests and refine existing assays. As we are constantly striving to improve our phenotyping platforms, we invite you to contact us to discuss your phenotyping needs and how MRC Harwell can assist you.
To request our services, please complete the resource enquiry form.
Our phenotyping services include:
Behavioural and Neurological Phenotyping
With an expanding platform of innovative tests, MRC Harwell is able to offer wide-ranging neurological phenotyping.
In recent years Harwell has built upon its established behavioural assays to develop more automated, long-term behavioural testing platforms. These tests enhance and augment the data generated by each individual short-term assay, thereby building a comprehensive insight into the effects of gene mutations on animal behaviour and neurological function.
Tests are available to measure activity, anxiety, circadian rhythm, sleep and neuromuscular function.
Automated phenotyping at Harwell:
With the Home Cage Analysis system, we are able to measure parameters such as locomotion, pair wise separation and time spent in isolation for up to three mice in their home-cage environment. This enables us to gain a unique insight into the light phase activity of mice and analyse differences in activities of various background strains over the light-dark cycle. Through machine learning, behaviours such as climbing, drinking and social interactions can be automatically annotated without experimenter intervention over extended periods of time. The measurement and analysis of multiple parameters can be done simultaneously under group housed conditions, making this a powerful tool in the identification of novel behaviours.To request our services, please complete the In Vivo Phenotyping Resource Enquiry form.
To read more about the home cage analysis system see the publication attached below:
Bains, Rasneer S. et al. “Analysis of Individual Mouse Activity in Group Housed Animals of Different Inbred Strains Using a Novel Automated Home Cage Analysis System.” Frontiers in Behavioral Neuroscience 10 (2016): 106.
MRC Harwell offers a range of in vivo and ex vivo tests to profile metabolic changes
With an interest in type II diabetes and obesity, MRC Harwell has a range of sophisticated equipment for measuring metabolic states both in unchallenged mice and in cohorts under dietary control. Technical staff at Harwell are also trained in a range of tolerance tests (including glucose and insulin) and efficient blood-sampling for clinical chemistry.
Specialist caging is also available for calorimetry measurements, food and water intake and urine and faeces collection.
To determine the metabolic activity of the mice, it is necessary to measure this indirectly through recording changes in oxygen and carbon dioxide levels in a sealed cage containing a singly- housed mouse. This test can be done over one night or a number of nights, and can be done in conjunction with the measurement of other parameters that affect metabolism for example activity, food and water consumption, temperature and also looking at the effect of the circadian cycle on metabolism.
Click here for information about our Clincal pathology services.
MRC Harwell offers a range of tests to interrogate the neuromuscular function
With an interest in neuromuscular function and ataxia, MRC Harwell has a range of sophisticated equipment for measuring various subtle aspects of muscle co-ordination, analysis of gait and also assess changes in muscle tone. Through a combination of tests, combined with behavioural studies as well, we able to build a broad picture of the neuromuscular system within a genetically altered line.
We have a range of equipment for assessing activity. This includes the Phenomaster Wheel Running set up, where mice are singly housed for a period of time from one night up to three weeks in a cage with a wheel. After a period of time acclimatising to the presence of the wheel, it is changed for one with fewer rungs and altered gaps between the rungs, presenting a significant challenge to the mice.
MRC Harwell offers tests for both hearing and vision
With a long-standing interest in hearing research, Harwell has developed a sophisticated platform which measures very subtle deficits in mouse hearing. In combination with ophthalmology, these tests reveal the sensory profile of the mouse line being studies.
As sensory inputs in the mouse can have key effects on a wide range of other phenotypes, we routinely establish the integrity of these systems prior to any in-depth neurological studies.
We have a range of equipment that enables us to examine the eye in detail. This includes a slit lamp and an opthalmoscope to observe the front and the back of the eye. In addition, we also have an Optical Coherence Tomography set up. The OCT allows us to image both the front and the back of the eye in much more detail, so that we can capture images of the fundus and annotate the retinal layers as well. We are also able to recreate 3-dimensional images of the eye to enable visualisation of abnormalities.
In order to examine the hearing range of the mice in detail, we perform the Auditory Brainstem Response test on anaesthetised mice. Sound tones of increasing volume at different frequencies are played via a speaker and the electrical activity of the brain is then recorded. A specific waveform is elicited in response to sound and this helps us to determine the threshold at which a mouse can hear a particular frequency.
Click here to see how sensory phenotyping has been used in the Deafness research programme here at the Harwell Institute.