SPONTANEOUS DISEASES IN GERMFREE ANIMALS* 
Morris Pollard* 
Germfree rats and mice have been propagated and 
maintained in colony form during the past 12 years. 
The methodology, as evolved during the past 35 years, 
has been so standardized and simplified that research 
programs can now be implemented with them in almost 
any biological laboratory. Germfree animals are com- 
parable to the conventional counterpart animals from 
which they had been derived, as regards reproduction 
patterns, litter sizes, growth rates, and appearances. The 
bacteria-free status of germfree animals is associated 
with a dilated, thin-walled, intestinal tract, and rela- 
tively inactive immunogenic mechanisms. Except for 
mice with congenital diseases (viral and non-viral), the 
spontaneous diseases encountered in germfree mice and 
rats have been of relatively low incidenqe, and their 
longevity has been extended. Germfree animals are free 
of "horizontally"-transmitted infectious agents. Three 
"vertically"-transmitted viruses, and associated diseases, 
have been observed among germfree mice: leukemia, 
mammary tumor, and lymphocytic choriomeningitis vi- 
ruses. A unique spontaneous "wasting" disease has been 
observed in germfree AKR mice. Thus far, no viral 
agent has been detected among germfree rats; however, 
as they aged they manifested, predominantly, increased 
numbers of adenomas in endocrine organs. Malignant 
tumors among them have been very rare. None of the 
classical tissue lesions, described in aged conventional 
rats, has been observed in the germfree rats. Germfree 
rats and mice are susceptible to experimental diseases 
resulting from exposures to chemical, physical, and 
biological agents. The syndromes thus induced in germ- 
free animals have been more clearly defined because of 
their isolation from the complicating effects of irrele- 
vant agents from the environment. They are excellent 
subjects for biomedical research. 
INTRODUCTION** 
The evolution of germfree technology during 
the past 70 years has resulted in the develop- 
ment of unique and defined experimental ani- 
mals and associated instruments for clinical 
applications.^'' Germfree rats and mice have 
been subjected to extensive examinations dur- 
* Lobund Institute, University of Notre Dame, Notre Dame, 
Indiana. 
** Supported by funds from U.S. Public Health Service Grant 
RR00294 and the John A. Hartford Foundation. 
ing the past ten years, as regards susceptibility 
to, and manifestations of, spontaneous and in- 
duced diseases. Viral agents have been found in 
germfree mice v^^hich necessitated coinage of 
the designation "gnotobiotic" (of known con- 
tent) to identify them. At the present time, 
there is no decisive evidence of a microbial flora 
in germfree rats; so that they are considered 
technically as germfree or axenic. For conven- 
ience they are referred to here as "germfree." 
This report concerns spontaneous diseases in 
germfree mice of seven strains and in germfree 
rats of three strains that have been propagated 
and maintained in this laboratory during the 
past 10 years (Table I) . 
CHARACTERISTICS OF GERMFREE MICE 
AND RATS 
Germfree rats and mice v^^ere derived from 
conventional mothers by caesarian delivery of 
fetuses from the uterus directly into a sterile 
plastic or steel container v^^hich is referred to as 
an isolater.*" The original babies v^^ere fed a 
sterile liquid diet by stomach tube up to v^ean- 
ing age; and thereafter, they sustained them- 
selves on a sterile solid diet and v^^ater. They 
have been maintained and propagated continu- 
Table I. — Strains of Germfree Mice and Rats at Lo- 
bund Institute 
Strain 
Source 
Generation in 
germfree 
status 
Mice: 
Swiss- Webster 
Harlan Farms 
45 
CFW 
A. Werder 
36 
C3h/f 
H. B. Andervont 
16 
Balb/c 
H. B. Andervont 
27 
AKR 
John Trentin 
28 
Haas 
Wallace P. Rowe 
22 
SJL/J 
Sam Poiley 
8 
Rats: 
Wis tar 
Wistar Institute 
30 
Sprague-Dawley 
Charles River Laboratories 
21 
Fischer (inbred) 
Andrew Schmidt 
7 
1005 
