Phenotyping Protocols for Pipeline: KMPC late adult KMPCLA_001

Week 53
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Combined SHIRPA and Dysmorphology KMPCLA_CSD_003 SHIRPA and dysmorphology were originally always separate assessments.  However they have recently been combined as assessments, so that they take place at the same time.The purpose of the assessments is to examine mice for obvious physical characteristics, behaviors and morphological abnormalities.Descriptions include abnormal locomotion/appearance/behavior/reflex reactions.
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Open Field KMPCLA_OFD_001 The Open Field test is used to assess anxiety and exploratory behaviors. It is based on the natural tendency of an animal to explore and to protect itself using avoidance which translates to a normal animal spending more time in the periphery of the Open Field arena than in the center (the most anxiogenic area).
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Grip Strength KMPCLA_GRS_001 The grip strength test is used to measure the neuromuscular function as maximal muscle strength of forelimbs and combined forelimbs and hind limbs. These are assessed by the grasping applied by the mouse on a grid that is connected to a sensor. Three trials are carried out in succession measuring forelimb-strength only, followed by three successive trials measuring the combined forelimb/hindlimb grip strength. All grip strength values obtained are normalized against mouse body weight.Ontological description: MP:0001515 - abnormal grip strength.
Week 54
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Acoustic Startle and Pre-pulse Inhibition (PPI) KMPCLA_ACS_003 The acoustic startle response is characterized by an exaggerated flinching response to an unexpected strong auditory stimulus (pre-pulse). This response can be attenuated when it is preceded by a weaker stimulus (pre-pulse) and is the principle underlying pre-pulse inhibition (PPI). PPI has been described in numerous species, including mice and humans and provides an operational measure of sensorimotor gating reflecting the ability of an animal to successfully integrate and inhibit sensory information. Several clinical studies have shown that a number of human disorders have impaired PPI including: schizophrenia, Huntington’s disease, fragile X syndrome, and autism. The acoustic startle and PPI paradigm is therefore largely used to assess sensorimotor gating and the effects of a number of treatment modalities such as putative anti-psychotics, and to explore genetic and neurobiological mechanisms underlying behaviors of relevance to psychosis (Geyer, 1999; Ouagazzal et al., 2001).Ontological description: MP:0002067 - abnormal sensory capabilities/reflexes/nociception.
Week 55
Indirect Calorimetry KMPCLA_CAL_003 Indirect calorimetry provides detailed information on the energy metabolism of mutant mice. Energy expenditure is evaluated through indirect calorimetry by measuring oxygen consumption with an open flow respirometric system. CO2 and O2 sensors measure the difference in CO2 and O2 concentrations in air volumes flowing through control or animal cages. The amount of oxygen consumed over a given period of time can thus be calculated, as far as the air flow through the cage is known. Data are expressed as ml O2 h-1animal-1. The system also monitors CO2 production, therefore, the respiratory exchange ratio (RER) and heat production can be calculated. An activity and food and water intake monitoring system can also be integrated into the set up in order to investigate circadian pattern and behaviour.Ontological description: MP:0005266 - abnormal metabolism.
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Electrocardiogram (ECG) KMPCLA_ECG_002 To provide a high throughput method to obtain Electrocardiograms in a conscious mouse.
Week 57
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Intraperitoneal glucose tolerance test (IPGTT) KMPCLA_IPG_001 The glucose tolerance test measures the clearance of an intraperitoneally injected glucose load from the body. It is used to detect disturbances in glucose metabolism that can be linked to human conditions such as diabetes or metabolic syndrome. Animals are fasted for approximately 16 hours, fasted blood glucose levels are determined before a solution of glucose is administered by intra-peritoneal (IP) injection. Subsequently, the blood glucose level is measured at different time points during the following 2 hours.Ontological description: MP:0005559 - increased circulating glucose level, MP:0005560 - decreased circulating glucose level, MP:0005293 - impaired glucose tolerance, MP:0005292 - improved glucose tolerance, MP:0005291           abnormal glucose tolerance, MP:0000188 - abnormal circulating glucose level.
Week 58
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Auditory Brain Stem Response KMPCLA_ABR_002 Auditory brainstem response test determines hearing sensitivity and other physiological parameters using evoked potential recordings in anesthetized mice.Ontological description: MP:0004738 - abnormal brainstem auditory evoked potential.
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X-ray KMPCLA_XRY_001 Construct and analyse digital X-ray images in immobilised mice using a Faxitron X-Ray system or NTB digital X-ray scanner.
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Body Composition (DEXA lean/fat) KMPCLA_DXA_001 Measure bone mineral content and density as well as body composition in mice using the DEXA (Dual Energy X-ray Absorptiometry) analyser.
Week 59
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Week 60
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Clinical Chemistry KMPCLA_CBC_003 Clinical chemistry determines biochemical parameters in plasma including enzymatic activity, specific substrates and electrolytes. Ontological description: MP:0001545 – blood physiology abnormalities.
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Hematology KMPCLA_HEM_002 Hematological assessment of blood determines blood cell counts (white blood cells, red blood cells, hemoglobin, and platelets) and additional hematological parameters (hematocrit, mean cell volume, mean corpuscular hemoglobin, mean cell hemoglobin concentration) can be derived using these indices. These tests will indicate abnormalities in the production of blood and its components (blood cells and hemoglobin) as well as in the associated blood-forming organs. Ontological description: MP:0002429 - abnormal blood cell morphology/development.
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Gross Pathology and Tissue Collection KMPCLA_PAT_002 To perform a complete necropsy to detect and record abnormal external findings and macroscopic alterations in internal and external organs, record body and heart weights (see IMPC Heart Weight SOP), and collect a standardized list of tissues for fixation with or without further processing (see non-mandatory IMPC Tissue Embedding & Block Banking SOP).
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Tissue Embedding and Block Banking KMPCLA_BLK_001 Collect and fix a standard list of tissues from the complete necropsy (see IMPC Gross Pathology & Tissue Collection SOP)Trim the fixed tissues into cassettes for processingEmbed the tissues in paraffin in a standard orientation
Insulin Blood Level KMPCLA_INS_003 The insulin concentration in the blood is an important indicator of diabetes.Ontological description: abnormal circulating insulin level [MP:0001560]; increased circulating insulin level [MP:0002079]; decreased circulating insulin level [MP:0002727].
Unrestricted
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Body Weight KMPCLA_BWT_001 The body weight test measures the weight of the mouse in a time series, allowing monitoring of its evolution; also, it is required in many other procedures.