Neurological Disorders – Spinal Muscular Atrophy – Animal Models, Severe and Mild
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Spinal muscular atrophy (SMA) is a rare autosomal recessive motor neurodegenerative disease and is the leading genetic cause of death among infants and toddlers. Several mouse models have been developed and scientists at PsychoGenics have contributed to the behavioral characterization of several of them. PsychoGenics has established a large colony of the SMNΔ7 neonatal and the C/C adult mouse models of SMA. The SMNΔ7 neonatal model has been well phenotyped and characterized in our facility (El-Khodor et. al. 2008). By using our in vivo neonatal drug screening platform, PsychoGenics can evaluate new chemical entities, biologics and gene therapies in the SMNΔ7 neonates.
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Spinal Muscular Atrophy – Body Weight
The body weight of the mice is recorded on a daily basis from birth to postnatal day 22.
Body weight from birth to postnatal day 22. KO mice weighed less than either group of control mice at the time points indicated*. Data expressed as means + SEM.
Spinal Muscular Atrophy – Hind-Limb Suspension Test (a.k.a. the tube test)
The hind-limb suspension test (HLST) is a novel non-invasive motor function test specifically designed for neonatal rodents. It evaluates the proximal hind-limb muscle strength, weakness and fatigue in mouse or rat neonates. The test is generally performed in 2 consecutive trials. In each trial, the mouse is placed head down, hanging by its hind limbs in a plastic 50 ml centrifuge tube with a cotton ball cushion at the bottom to protect the animal’s head upon its fall. Three parameters are evaluated: a) Latency to fall from the edge of the tube (sec) b) Number of pulls that the animal performs during its attempt to escape the tube and c) Hind-Limb Score (HLS) which assesses the positioning of the legs and tail.
Hind-limb score in the tube test.SMNΔ7 (KO) animals shows a significant motor deficiency as evident in low HLS score. The tube test was administered in two consecutive trials from postnatal day 2 to 12. Values presented are mean + SEM; * p < 0.01.
Spinal Muscular Atrophy – Negative Geotaxis
This test evaluates motor coordination and vestibular sensitivity. Animals are placed head facing down on an inclined plane and latency to re-orient head up is recorded.
SMNΔ7 knockout (KO) mice showed marked impairment in geotaxis test when compared to littermate controls (WT and HET).
Spinal Muscular Atrophy – Survival
Animals were checked for survival twice per day from birth to postnatal day 22.
Kaplan-Meier cumulative survival curves. (A) SMNΔ7 (KO) mice compared to littermate controls (WT and HET). KO mice survived for a maximum of 17 days with 50% mortality at P12.
The total number of errors (including reference memory and working memory errors) decreases over 4 days of training.
