Sylics offers a variety of motor function tests.
Motor function (Spontaneous Behaviour)
Mice display a variety of spontaneous behaviours in our PhenoTyper automated home-cages (Noldus IT, The Netherlands), which are tracked at high resolution with video cameras. The cages are equipped with a shelter compartment, on which mice climb during bouts of activity during the dark phase (Loos et al 2014; Loos 2015). Mouse mutants with known motor function deficits, such as the SOD1 model of amyotrophic lateral sclerosis (ALS), show reduced or absent shelter climbing, an early detection of motor function deficits. Tracking of spontaneous behaviour in PhenoTyper cages is therefore a rapid and sentive method for assessing motor function.
Catwalk automated gait analysis system
The CatWalk XT (Noldus IT, The Netherlands) is a gait analysis system for quantitative assessment of gait and locomotion in mice. It is the most sophisticated system for quantification of a wide range of parameters related to footprints and gait in unforced moving animals. It is used by Sylics in various disease models, including spasticity, vanishing white matter, and neurodegeneration. For instance, subtle but reproducible changes in motor function are detected in the P301L transgenic tau model of Alzheimer’s disease.
The Balance Beam sensorimotor coordination test scores the ability of mice to traverse a stationary horizontal rod. Coordination of the mouse is measured by the latency to cross the beam and the number of foot slips made. Motor dysfunction affects balance beam performance. For example, a mouse model of Vanishing white matter (VWM) - a fatal leukoencephalopathy characterized by motor dysfunction - showed clear deficits on this task (Dooves et al., 2016)
The Rotarod is the golden standard of assessing motor performance and learning in mice. The mice are placed on a rotating rod, with increasing rotating speed. Motor performance is measured by the maximal RPM (rounds per minute) at which mice are able to keep up with the rotating rod. Motor learning can be assessed by training mice on the rod for several trials. Mouse models with neuromuscular dysfunction or neurodegeneration in motor-related brain regions show impaired performance in the Rotarod (Geerts et al. 2015).
Grip Strength Test
The Grip Strength test assessess neuromuscular function by measuring the peak force a mouse can apply by grasping a bar connected to a force meter. Five trials with front paws are followed by five trials with front and hind paws combined. The median of these five trials is used as measure of grip strength. Mouse models with impaired neuromuscular dysfunction show impaired performance in the Grip Strength test (Geerts et al. 2015). In addition, mouse models of vanishing white matter also have decreased grip strength (Dooves et al. 2016). The grip strength test can also be used in tau transgenic models to longitidinally follow the build up of toxic tau protein in the brain stem and spinal cord.
The Treadmill is a popular test to asses motor function, neuromuscular function, and fatigue in mice. Mice are motivated to run on a motorized treadmill equipped with a grid providing a mild stimulation. Based on the rotation speed over time and the time spent on the Treadmill, the total distance travelled can be calculated. This gives an indication of motor function, muscle performance, and endurance of the mouse. This test is for instance relevant in studies investigating treatments that putatively prevent loss endurance, muscle performance of general fitness in aging mice.
In the wire hanging test, the mouse hangs from an elevated wire or cage top. After the mouse has grasped the wire with its front paws, the time it takes for the mouse to release is recorded (Aartsma-Rus et al. 2014). Alternatively, the mouse is placed on the cage top, which is inverted, and the time it takes for the mouse to fall in the home cage is recorded. Mouse models with neuromuscular and motor impairments show decreased wire hanging ability.
Neurological motor scoring
Manual neurological motor scoring of mice is a rapid method to longitudinally assess motor dysfunction of mice. It assesses parameters like extension and trembling of the legs, toe curl and foot dragging, and ultimately (partial) paralysis. The neuroscore identifies impairments in mouse models with motor and neuromuscular dysfunction including tau models that carry a mutation (P301S or P301L) involved in dementia. Progressive impairments detected in a mouse model of vanishing white matter could be rescued with a therapeutic compound (Abbink et al 2019).
Vanishing white matter: deregulated integrated stress response as therapy target. Abbink TEM, Wisse LE, Jaku E, Thiecke MJ, Voltolini-González D, Fritsen H, Bobeldijk S, Ter Braak TJ, Polder E, Postma NL, Bugiani M, Struijs EA, Verheijen M, Straat N, van der Sluis S, Thomas AAM, Molenaar D, van der Knaap MS. Ann Clin Transl Neurol. 2019 Aug;6(8):1407-1422. doi: 10.1002/acn3.50826. Epub 2019 Jul 18. PMID: 31402619; PMCID: PMC6689685. https://pubmed.ncbi.nlm.nih.gov/31402619/
Keywords: VWM, Vanishing White Matter
Dooves S, Bugiani M, Postma NL, Polder E, Land N, Horan ST, van Deijk AL, van de Kreeke A, Jacobs G, Vuong C, Klooster J, Kamermans M, Wortel J, Loos M, Wisse LE, Scheper GC, Abbink TE, Heine VM, van der Knaap MS. Astrocytes are central in the pathomechanisms of vanishing white matter. J Clin Invest. 2016 Apr 1;126(4):1512-24. https://pubmed.ncbi.nlm.nih.gov/26974157/
Within-strain variation in behavior differs consistently between common inbred strains of mice. Loos M, Koopmans B, Aarts E, Maroteaux G, van der Sluis S; Neuro-BSIK Mouse Phenomics Consortium, Verhage M, Smit AB. Mamm Genome. 2015 Aug;26(7-8):348-54. doi: 10.1007/s00335-015-9578-7. Epub 2015 Jun 28. PMID: 26123533. https://pubmed.ncbi.nlm.nih.gov/26123533/
Sheltering behavior and locomotor activity in 11 genetically diverse common inbred mouse strains using home-cage monitoring. Loos M, Koopmans B, Aarts E, Maroteaux G, van der Sluis S; Neuro-BSIK Mouse Phenomics Consortium, Verhage M, Smit AB. PLoS One. 2014 Sep 29;9(9):e108563. doi: 10.1371/journal.pone.0108563. PMID: 25264768; PMCID: PMC4180925. https://pubmed.ncbi.nlm.nih.gov/25264768/
Tomosyn-2 is required for normal motor performance in mice and sustains neurotransmission at motor endplates. Geerts CJ, Plomp JJ, Koopmans B, Loos M, van der Pijl EM, van der Valk MA, Verhage M, Groffen AJ. Brain Struct Funct. 2015 Jul;220(4):1971-82. doi: 10.1007/s00429-014-0766-0. Epub 2014 Apr 18. PMID: 24744148. https://pubmed.ncbi.nlm.nih.gov/24744148/
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