Neurological Disorders – Amyotrophic Lateral Sclerosis
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Initial signs of ALS include muscle weakness occurring in approximately 60% of patients. As the disease progresses, weakness and paralysis spread to the trunk of the body and eventually speech, breathing, swallowing and chewing are affected. Only 10% of ALS is directly hereditary where patients have a close second family member with ALS. This is known as familial ALS (FALS). A mutation in the copper-zinc superoxide dismutase (SOD1) gene has been found in approximately 20% of patients with FALS.
SOD1 transgenic mice are used as a model for ALS. These mice have the mutant human SOD1 (G93A) substitution. Motor impairment is first observed at 12 weeks of age and includes changes in body weight, decline in grip strength and general motor activity, which can be assessed using the tests outlined below. This phenotype continues to decline until death at an average age of 19 weeks.
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Neurological Disorders – Amyotrophic Lateral Sclerosis – SOD1 *G93A Mouse – Body Weight
The body weight of the mice is recorded on at regular intervals throughout the duration of the study.
SOD1 (G93A) mice exhibit a decline in bodyweight beginning at 12 weeks of age in males and 16 weeks of age in females. Body weight continues to decline with disease progression.
Neurological Disorders – Amyotrophic Lateral Sclerosis – SOD1 *G93A Mouse– Grip Strength
Grip strength is used to assess muscular strength in limb muscles. The animal is lowered toward the platform and gently pulled backwards with consistent force by the experimenter until it releases its grip. The grip force is recorded on the strain gauge.
SOD1 (G93A) mice exhibit a decline in forelimb grip strength, beginning at around 9 weeks of age, and continuing to decline with disease progression.
SOD1 (G93A) mice exhibit a decline in hind limb grip strength, beginning at around 9 weeks of age, and continuing to decline with disease progression.
SOD1 (G93A) mice exhibit a decline in hind limb grip strength, beginning at around 9 weeks of age, and continuing to decline with disease progression.
Neurological Disorders – Amyotrophic Lateral Sclerosis – SOD1 *G93A Mouse– Rotarod
Motor coordination and exercise capacity are assessed by rotarod. Tests are performed on separate days, with multiple trials per day. Mice are placed on the rotarod and the speed is gradually and uniformly increased over a maximum period of time. The time that each mouse remains on the rotating rod before falling is recorded.
SOD1 (G93A) mice are observed to have a decline in motor function from 12 weeks of age, as assessed by the rotarod test.
Neurological Disorders – Amyotrophic Lateral Sclerosis – SOD1 *G93A Mouse– Survival
Survival of the mice is recorded and can be cumulatively tracked as the population in the various treatment groups decline.
SOD1 (G93A) mice begin to show decreased survival from as early as 120 days (approximately), with an increasingly steep decline and zero survival at around 150 days.
Ceftriaxone-treated SOD1 (G93A) mice are seen to have significantly greater survival compared to saline treated controls.
The total number of errors (including reference memory and working memory errors) decreases over 4 days of training.
