The causes of human
amyotrophic lateral sclerosis (ALS) and the spinal
muscular atrophies (SMA) are, almost without exception, unknown. This ignorance has stimulated the search for animal models to obtain insight into the etiology, pathogenesis and biochemical mechanisms underlying the human disorders. None of the 38 animal models, described in this review, provides an exact animal copy of a specific human
motor neuron disease. Most of the models reproduce certain structural or physiological aspects of their human counterparts. The various experimental models can be classified according to the pathogenetic mechanism involved and according to the structural changes observed. Models based on experimentally induced disease, include
heavy metals and
trace elements (lead intoxication in guinea pigs, rabbits, rats, cats and primates;
mercury intoxication in rats;
aluminium intoxication in rabbits;
swayback in goat kids;
calcium and
magnesium deficient rabbits and primates and
calcium deficient cynomolgus monkeys), toxins (IDPN,
vincristine,
vinblastine,
podophyllotoxin,
colchicine,
maytansine,
maytanprine,
L-BMAA,
lectins,
adriamycin), nutritional factors (
ascorbic acid deficient guinea pigs),
virus infection (spongiform polioencephalomyelitis, attenuated poliovirus, lactate dehydrogenase-elevating virus), and
immunological factors (immunization with motor neurons). Hereditary models comprise hereditary canine
spinal muscular atrophy, hereditary neurogenic amyotrophy in the pointer dog, Stockard
paralysis, Swedish Lapland dog
paralysis, "wobbler" mouse, "shaker" calf, and hereditary
spinal muscular atrophy in zebra foals, crossbred rabbits,