444 BIOLOGY OF THE LABORATORY MOUSE 



Intracerebral injection of mice with other agents (109, 270) has resulted 

 in the isolation of the most virulent strains of the virus yet obtained. No 

 relationship could be established between the strain of murine encephalo- 

 myelitis isolated and the agents injected (the viruses of yellow fever and 

 human encephalitis) , so that exacerbation of a latent infection seems to be 

 the most likely explanation. The signs of infection were entirely similar to 

 those resulting from experimental intracerebral inoculation of known strains 

 of the virus. 



The experimental disease. — The production of clinical disease by 

 experimental inoculation of the virus depends on the virulence of the strain 

 of virus, the route of inoculation, and the age of the mice. With strains of 

 relatively low virulence — those obtained from intestinal contents of normal 

 mice or the central nervous system of naturally infected mice — intracerebral 

 injection of young animals gives a high morbidity and mortality, whereas by 

 intranasal inoculation only a low incidence of paralysis occurs. Other routes 

 are ineffective (268, 269, 270, 88, 189). With strains of higher virulence 

 (109, 270), however, signs of involvement of the central nervous system 

 occur following intracerebral, intranasal, and intraperitoneal injection with 

 greater regularity, and occasionally following subcutaneous inoculation. 

 The influence of age is shown by the fact that the morbidity and mortality 

 rates are lower and the incubation time longer in mice over 12 weeks of 

 age (270, 84, 109). 



After intracerebral injection (268, 269, 88, 109, 270), a period of 5 to 

 30 days may elapse before the appearance of signs of the disease, but the 

 average time is 10 to 14 days. The first sign is a weakness of one limb, 

 rapidly followed by flaccid paralysis of that member. The paralysis may 

 spread to involve all four legs, but usually the hind limbs are more markedly 

 affected so that locomotion is possible only by use of the fore legs. Atrophy, 

 emaciation, and contractures of the involved members occur. Incontinence 

 of urine may be observed in severely aftlicted animals. In spite of the above 

 evidence of damage to the nervous system, the mice do not appear acutely 

 ill during the first stages of the disease. Finally, however, the fur becomes 

 ruffled, respiration labored, and the animal succumbs. Mice 4 weeks of age 

 or younger, however, may die without showing signs of infection. If 

 recovery occurs, the extent of the involvement diminishes, but residual 

 paralysis of the hind limbs is almost constantly present. Such recovered 

 animals may harbor the virus in the spinal cord for more than a year (269). 

 The duration of the disease from the first appearance of clinical signs to death 

 or recovery varies between 2 and 10 days. Following other routes of 



