448 BIOLOGY OF THE LABORATORY MOUSE 



Virus pneumonia in mice. — Mice are being widely used for the investiga- 

 tion of certain human respiratory infections, such as influenza, because these 

 animals respond to intranasal administration of the causative viruses with 

 the production of pneumonic consolidation. In the isolation of the virus 

 from nasopharyngeal washings from the patient, however, it is often neces- 

 sary to make several "blind" passages of lung tissue from the first animal 

 before the mice develop extensive lesions or die from the infection. An 

 infectious agent, latent in the experimental animal, could thus be carried 

 along during the successive passages, and increasing in virulence, could 

 finally produce obvious disease. In this manner three different groups of 

 investigators (54, 89, 103, 104) have encountered respiratory disease which 

 differed from that seen with known viruses. They have further shown that 

 the disease may be produced by repeated serial passage of lung tissue from 

 apparently normal healthy mice, which indicates that a certain percentage 

 of mice harbor the responsible agent. Two types of disease have been 

 found, differing somewhat in course, host susceptibility, and production of 

 immunity, although the possibility of immunological relationship between 

 the respective viruses has not yet been determined. For the sake of 

 simplicity, therefore, the two types will be described separately. 



No instances of spontaneous illness due to either type of infection have 

 been reported, although the viruses have been found in albino Swiss mice as 

 young as 3 weeks of age, and in other albino strains obtained from a number 

 of different sources. Small areas of spontaneous pulmonary consolidation 

 occur in such animals with varying frequency: i to 2 per cent (104) and 35 

 per cent (54). The viruses must accordingly have a fairly wide distribution 

 and a low virulence under natural conditions. Increase in virulence of the 

 agents with successive intranasal passage would then account for the produc- 

 tion of extensive and often fatal pneumonic lesions. 



Pneumonia described by Dochez, Mills, and Mulliken (54), and by 

 Gordon, Freeman, and Clampit (89). — This form of experimental pneu- 

 monia, first described by Dochez, Mills, and Mulliken (54), appeared after 

 I to 9 intranasal passages. Clinically, the signs of infection were loss of 

 activity, refusal of food, ruffled coat, and hunched posture, with the develop- 

 ment of rapid, labored respirations as the disease progressed. Deaths began 

 to occur after 4 to 7 passages, the mice succumbing 2 to 4 days after inocula- 

 tion. The mortality rate was high; in fact, all mice (5 to 10 grams in weight) 

 developing signs of infection died (89). 



At autopsy the only significant lesions were found in the lungs. Early in 

 the course of the disease, sharply demarcated, greyish-pink areas of con- 



