2004A0042 - Drug Screening in ALS - Valerie Bergdall
Pain Code = 3E
Species = 1,780 Mice

The SOD1 G93A mouse model of ALS was developed in 1996. This mouse carries a human mutant gene that is found in a small population of ALS patients. Using the Mouse model the PI hopes to "identify genes, drugs and treatments that can significantly slow the onset of paralysis and enhance survival."

The PI states that "only the development of an animal model to induce localized lesions in the spinal cord can address the issue of initiation and propagation of ALS."

Here is how an animal dealer who sells this mouse describes "their product"

Strain Description
The transgenic insert carries a high copy number of the mutant allele human SOD1 containing the Gly93 -->Ala (G93A) substitution. Hemizygous transgenic mice become paralyzed in one or more limbs and have a life span of approximately 19-23 weeks. Paralysis is due to loss of motor neurons from the spinal cord.

"The SOD1 mouse show evidence of paralysis at the end stage of the disease. The paralysis involves only motor neurons and hence, even in the paralysis situation when they do not move much, they do not demonstrate pain. Paralysis will be monitored using a 5 point scale. This is the only way to measure drug efficancy and life extension and hence it is critical that these animals be maintained alive until they are no longer able to right themselves within 30 seconds when placed on their sides. This will be (the) final endpoint when the animals will be euthanized."

"SOD1 G93A mice are born normally with normal growth rate. ... It is only at 100-130 days of age that they start showing neurological abnormality. In earlier stages, these animals when lifted by their talis stop splaying their hind limbs as normal wild type animals do. Within weeks of this, they start to show evidence of paralysis and start dragging their hind limbs. They continue to move around with their fore limbs for about 1-2 weeks and then become so paralyzed that they are unable to move and right when placed on their sides in 30 seconds. At this stage the animals are no longer able to get to the wet food supplied with in the cage and are euthanized."

"The paralytic mice are carefully monitored daily to ensure that starvation does not cause the death in these animals."

Scoring

• Score 0 = Normal animal with normal splaying of hind limbs when lifted by the tail (floor reaching reflex)
• Score 1 = (About Day 100-125 of age) Abnormal reflex. The animal shows diminished splaying reflex although can freely move about the cage and rear up on its hind limbs. These animals feed, grrom and drink without any trouble.
• Score 2 = (About Day 125-140 of age) Abnormal reflex and evidence of paralysis. The animal shows poor splaying reflex and also poor placement of their hind feet when moving about in the cage. Their hind limb movement is sluggish and uncoordinated.
• Score 3 = (About Day 125-145 of age) No reflex and paralysis. These animals show no splaying reflex and have hind limb paralysis. Their fore limbs are still functional. They can not reach food and water via standard feeders/dropper and hence wet food is provided inside the cage. A large sipper tube is provided so that the animals can reach the water more easily.
• Score 4 = These animals can not right themselves when they are placed on their sides in 30 seconds. The animal is unable to move completely and can not reach the wet food. The animals are euthanized at this point.

"The scoring system decribed above is routinely used by many labs to monitor the SOD1 G93A mice. Although these animals show discomfort they do not appear to show evidence of pain or distress. This is because their motor function is the only system affected and their sensory system is still intact."