1008 
ANIMAL DISEASES 
the unique lesions of hemolytic anemia and reti- 
culum cell sarcoma, respectively, have not been 
clarified, and the pathogenesis of both syn- 
dromes appear to be regulated by genetic mech- 
anisms. 
Aside from the diseases noted above, seba- 
ceous cysts, hernias, and neoplasms have been 
observed occasionally in other strains of germ- 
free mice (Table II) ; hov^^ever, the great major- 
ity of them live without apparent disease. Amy- 
loidosis has been observed rarely in Lobund 
strains of germfree mice. While most strains of 
germfree mice are rarely handicapped by the 
enlarged cecum, this laboratory has the impres- 
sion that this enlarged organ may be responsi- 
ble for the poor reproduction records of C57 BL 
and SJL/J mice that exist in this Laboratory. 
Eperythrozoon coccoides has been detected in 
the blood cells of commercially-available strains 
of germfree micei^" but an extensive survey 
has failed to reveal this organism in Lobund 
germfree mice.^^ 
SPONTANEOUS DISEASES IN GERMFREE RATS 
A survey of aged germfree Lobund Wistar 
rats (>24 months) in 1962 revealed that many 
of them v^ere afflicted with nephrosis, plus some 
benign and malignant breast tumors.^- In a 
subsequent survey of aged germfree rats, nei- 
ther nephrosis nor malignant neoplasms were 
found among them.^^ ^* Their tumors were be- 
nign and localized, and involved predominantly 
endocrine-related organs and occasional lipomas 
(Table III). In order of increasing frequency, 
the organs involved with benign tumors have 
been thyroid, thymus, liver, pituitary, breast, 
and adrenal glands. The percentage of rats with 
detectable tumors increased from 0 at age 12 
months, 16 at 15 months, 30 at 20 months, 56 at 
25 months to 77 at age 30 months. In one male 
germfree Wistar rat killed at age 31 months, 
benign adenomas were observed in the thymus, 
adrenal, pituitary, liver, and thyroid glands. In 
a second male germfree Wistar rat, killed at the 
same age, benign adenomas were observed in 
the pituitary and adrenal glands. 
The lymph nodes of aged germfree rats con- 
tain rare germinal zones, but unusual cords of 
plasma cells have been observed in the medul- 
lary areas. The data recorded in Table III 
would suggest that tissue lesions appear in 
germfree rats at or after 25 months of age. This 
might be misleading, except for those lesions 
which were visible externally (i.e., tumors of 
the breast). Rats with large pituitary tumors 
have had locomotor difficulties, but the other tu- 
mors induced no significant clinical manifesta- 
tions. Specified tissue lesions have been re- 
corded by others as "hallmarks" of the aging 
rat: they included nephrosis, degeneration of 
cardiac and skeletal muscles, and polyar- 
teritis. In addition to the data record- 
ed on Wistar rats in Table III, the so-called 
aging lesions have not yet been observed in 
germfree Sprague-Dawley and Fischer strain 
rats {Table IV). 
Table III. — Spontaneous lesions in Germfree Wistar rats 
Age/months* 
12 ± 2 
15 ± 2 
20 ± 2 
25 ± 2 
30 ± 2 
Total 
Number 
36 
12 
10 
60 
13 
131 
Sex: Male-Female 
25-13 
2-10 
10-0 
37-23 
10-3 
82-49 
No lesions: Male-Female 
23-13 
0-1 0 
7-0 
19-18 
2-1 
51-42 
Monocytic leukemia 
1-0 
1 
Adenomafibroma of breast 
7(5)_2 
2'»-0 
11 
Adenoma - adrenal 
l(i)*»_0 
3-0 
10-2 
4<i'-0 
18 
pituitary 
1-0 
2-1 
4-2 
10 
thymus 
1-3 
2«>-0 
6 
liver 
2-0 
4(i)_0 
6 
thyroid 
1-1 
2-0 
4 
lung 
1-0 
1-0 
2 
Lipoma 
3W-0 
0-1 <i> 
4 
% of rats with tumors 
0 
16 
30 
66 
77 
62 
* One rat with fibrosarcoma has been observed at age 7 months. 
** (1) indicates number of rats with more than one lesion. 
