1010 
ANIMAL DISEASES 
have manifested lesions resulting from specific 
nutritional deficiencies,*^ except that they can 
tolerate acute deficiencies of vitamins A-*- and 
C. A small number of germfree Wistar rats, fed 
a standard diet supplemented with 5% sucrose 
in v^ater, developed cardiovascular lesions 
vi'hich v^^ere absent in control rats on the same 
diet, but vi^ithout sucrose vi^ater.*^ Germfree 
rats were free of dental caries, unless they had 
been maintained on sucrose water and contami- 
nated with a cariogenic bacterium such as 
enterococci.** Germfree rats should provide 
unique advantages for determining the patho- 
genic potential of dietary sucrose. 
DISEASE CONTROL IN GERMFREE ANIMALS 
The incidences of spontaneous diseases in 
germfree mice have been relatively low ; but it 
has been impossible to control the specific 
strain-related virus-induced diseases in AKR 
and Haas mice. In the latter strains, as in 
strains NZB and SJL/J, the disease manifesta- 
tions were not modified by the germfree status 
of the host. The diseases recorded in the 4 
mouse strains noted above constitute definite 
life-limiting factors. The development of spon- 
taneous malignant tumors in mice limits their 
value as experimental subjects. In addition, the 
universal "C"-type virus infection in all mice 
thus far examined confuses their causal rela- 
tionships to chemical-induced neoplasms by 
appearing in or on the tumor cells as "pas- 
sengers. "^^ Germfree mice have few dis- 
eases unique to their germfree status. The only 
strain-related condition thus far detected is the 
spontaneous "wasting," a disease of germfree 
AKR mice. All others are related to congenital- 
ly-controlled disease mechanisms which appear 
in both germfree and conventional stock. Germ- 
free mice and rats live longer than their con- 
ventional counterparts*^'''^ and are spared the 
disease complications derived from the exogen- 
ous bacterial flora. The great benefits in most 
strains of germfree mice relate to the low level 
of spontaneous diseases that they develop in a 
controlled gnotobiotic environment and to their 
survival following such procedures as neonatal 
thymectomy,*^ whole-body x-irradiation,*^'°" im- 
munosuppression by drug actions^^*" and 
radiation-induced bone marrow chimerism.^^ 
The enlarged cecum may be considered abnor- 
mal, but it is infrequently a disease factor in 
most strains of mice. 
In contrast to mice, no infectious agent has, 
as yet, been detected in germfree rats. They de- 
velop, spontaneously, benign adenomas of endo- 
crine-related organs which may eventually turn 
malignant, although there is no evidence to sub- 
stantiate this. The lesions in the endocrine or- 
gans may conceivably produce a physiological 
dyshomeostasis, as a preamble to aging.*^ The 
absence of the "classical" lesions of aging in the 
germfree rats may reflect their insulation from 
cell-depleting toxic factors in the environment, 
with resultant sparing of stem cells which have 
repair or replacement functions. Since the 
strains of Lobund germfree rats do not have de- 
tectable congenital infections, the other modify- 
ing factors in their environment could come 
from diet, humidity, temperature, crowding, 
light, and noise. These have been controlled and 
rendered uniform by current practices of germ- 
free technology. In view of their low profile of 
spontaneous diseases, their longevity, the con- 
trolled environment in which they live, and 
their susceptibilities to induced diseases, germ- 
free rats are excellent, versatile, experimental 
subjects for bimedical research. 
SUMMARY 
The origins and characteristics of germfree 
mice and rats have been reviewed. Genetically- 
governed diseases in mice due to congenitally- 
transmitted viruses and to diseases of unknown 
etiology have been described. Three congenitally- 
acquired, life-limiting, virus infections have 
been described in germfree (gnotobiotic) mice, 
which cause specific diseases in three genetic 
strains of mice. Two strains of germfree mice 
(NZB and SJL/J) develop spontaneous dis- 
eases of unknown etiology, which usually kill 
them by age 12 months. Germfree rats are free 
of detectable microbial agents. As they grow 
older they spontaneously develop benign neo- 
plasms which affect predominantly endocrine 
organs. Germfree rats at age 24 months do not 
develop the classical lesions of aging which have 
been described in conventional rats. While they 
