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Labyrinthitis in the rat and a method for its control.

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The Wistar Institute of dnztowi!l and Biology, I’hiludclphia, Pennsylvania
Various pathological conditions found in the ear of the
rat have been reported under the name ‘middle ear disease.’
Investigations to determine the cause of this disease have
given no very decisive results, since infected ears usually
contain a wide variety of micro-organisms and it has been
impossible, as yet, t o definitely identify the ones responsible
for the malady (Casarnajor, ’14; iUcCordock and Congdon,
’24; Bradford, ’28; Turner, ’29; Nelson, ’30 a).
The bacteria found most frequently in diseased ears are
diphtheroids, streptococci and B. actinoides. When, however,
pure cultures of these organisms have been introduced into
the tympanic cavity of normal ears, they have produced a
serous o r purulent exudate in some cases, but no specific
reactions have followed in other iiistaiices (Nelson, ’30 b).
B. actinoides and streptococci are regarded by Nelson ( ’30 a )
as potentially capable of inducing middle ear disease, but
he states: “There is also the the possibility that the condition has its origin in some form of irritation other than a
bacterial one, and that all the bacteria isolated from the
diseased ear are secondary invaders.”
It has been suggested that vitamin-deficient diets, or those
lacking certain mineral salts, so lower the natural resistance
of the rats that they bwome very susceptible to ear infection
(Daniel, Armstrong anti Rutton, ’23 ; McCordock and Congdon,
’24; Bradford, ’28; Turner, ’29). However, subjecting rats
free from ear disorder to a rachitic diet and t o over-crowding
does not predispose {hem to aural infection (Nelson and
Gowen, ’30). In many cases rats receiving an adequate diet
have appeared vigorous and healthy f o r many months, yet
morbific conditions in the ears have heen discloved at autopsy.
On the whole, the investigations that have been reported
seem to cast some doubt on the probability that any single
organism is responsible f o r ear disease. Possibly the condition is a non-specific one in which a number of different
organisms are involved.
No attempts to determine the etiology of ear disease have
been made in the laboratories of The Wistar Institute. The
purport of this paper is to describe one form of ear infection,
commonly included under middle ear disease, that markedly
affects the behavior and health of rats, and to give a method
of procedure by which it bas been eliminated, seemingly,
from a large colony of albino rats in which it was prevalent
for many years.
The type of ear disease here considered has often been
called ‘mastoid disease.’ More properly it should be termed
‘labyrinthitis, ’ since the disequilibration and circular movements of afflicted individuals indicate that the main seat of
infection is in the internal ear and not in the tympanum.
Clinical symptoms of labyrinthitis are definite and distinctive. The first indication of its presence is a slight tilting
of the head to one side. Subsequently the rat holds its head
continually close to the floor of the cage, with the nosc pointing away from the medial line. Lack of coordination in
muscular rnovements is shown by the fact that the individual
is unable to run in a straight line, but does so in a curve.
It may stagger as it runs, and if it falls on one side has
difficulty in regaining an upright position. When suspended
by the tail, the body invariably rotates rapidly. Because of
this latter characteristic rats with labyrinthitis are often
called ‘twisters.’
Necropsies on a large number of rats with this disease
have shown that the labyrinth of one or of both ears is always
filled with a thick, creamy pus, and that the tympanum may
contain a liquid or purulent exudate, although it often appears
normal. Tn advanced ca3es lesions of the tympanic and petrous
bones occur, and the inFection passes up the branches of the
auditory nerve to the brain where it produces degeneration
of the nerve roots or abscesses and eventually causes death.
Labyrinthitis rarely appears in rats less than 3 months
of age, usually it is found only in adults and less frequently in
females than in males. Infected females are able to produce
and rear young, but the offspring are often very small at
birth and many of them diet a t an early age.
A strain of closely inbred albino rats has been maintained
a t The Wistar Institute since 1909. F o r many generations
these rats were exceptionally large and vigorous, and the
only disease prevalent among them was the lung infection, socalled pneumonia, which frequently attacks rats of any race
after they have passed their prime and are approaching
senility. Labyrinthitis first appeared in an individual of this
strain in 1918, when ral s of the twenty-sixth generation were
under investigation. .Qt this time the environmental and
nutritive conditions under which these rats were living were
very unfavorable for growth and repro’duction chiefly because
of war restrictions. It,is possible that these conditions so
lowered the vitality of the animals that they became very
susceptible to this ear infection which was introduced into
the strain ig some unknown way. Daring the next ten generations, only a few cases of labyrinthitis were noted, but subsequently it became more prevalent, and at the fiftieth generation about 10% of all adults showed diagnostic symptoms of
this disease. At this generation the investigation of various
life processes in individuals of the strain was temporarily discontinued, but was resumed in 1930 at the seventy-fifth generation. After this work had been in progress a few months it
was found that over 40% of all adults had labyrinthitis and
that early symptoms of this disease were being shown by
many rats less than 3 months of age. The growth and reproduction of the rats were so markedly affected that it became
impossible to continue the investigation. After this time
the number of inbred rats was greatly reduced, and all adults
were killed after suitable litters had been reared for a continuation of the strain.
I n 1931 Nelson and Gowen published a method of procedure
by which they were able to establish a colony of albino rats
free from middle ear disease. They selected for breeding
stock offspring from parents that had been killed after the
young were weaned a n d found to be free from ear infection.
These rats were then isolated from the general stock, in
which there was a high incidence of middle ear disease, and
formed the nucleus of a colony in which no aural iiifectioii
ever occurred. The results of this experiment indicated the
possibility that one of tlie ways by which ear disease is diffused
among the individuals in a colony might be its transmission
from a n infected mother to her offspring during the suckling
It had been noted that the incidence of labyrinthitis was very
low in the strain of captive gray Norway rats housed for over
10 years in the same room with the inbred albinos. Only five
males and one female with this disease were found in over
3000 adults reared for a study of life processes. Autopsies
on hundreds of gray rats, made when they were 20 months of
age, failed to dislcose a single individual with infection in the
labyrinth. although the tympanum of some rats contained a
liquid exudate.
As the work of Nelson and Gowen (’31) pointed to a way
by which, possibly, the inbred albinos might be saved from
extermination by labprinthitis, experiments were undertaken
to see if any favorable results would be obtained if gray
females were used as foster mothers for young born in the
inbred strain. Fifteen litters from the seventy-sixth to the
seventy-niiith generation were taken from their mothers at
or soon after birth and their approximate postnatal age
recorded. Each litter was then placed in a cage with a lactating p a ) - female whose own offspring were killed. Six gray
females refused to care for these aliens, but the other females
accepted them and reared p a r t or all of the young they received. Tl’hen weaned, these albiiios werc lionsed in freshlv
sterilized cages and kept until they were at least 8 months old.
After this age, according to Nelson and Gowen ('31) the
morbidity rate of middle ear disease remains nearly stationary.
Rats in three litters that had been suckled by gray females
from the time they were born did not develop symptoms of
labyrinthitis during the period they were under observation.
Autopsies on several of them disclosed no ear infection. One
or more individuals in all other litters reared by gray females
became twisters when from 3 to 6 months old.
These preliminary experiments gave another very significant
result. Tm7o of the gray females serving as foster mothers
for albino young which had remained with their own mothers
for several hours after birth developed characteristic symptoms of labyrinthitis, and their internal ears were found to
contain pus. No other gray rats of the same generation had
labyrinthitis, although 0~7era 100 of them were under observation until they were 20 months old.
In subsequent work with the inbred albinos only young
adults that had not shown symptoms of this ear infection were
used as breeding stock, and all their offspring that could
be obtained at the time of birth, with the placenta still attached,
were suckled by gray females. These rats then formed the
breeding stock for the succeeding generations. None of these
albinos ever developed labyrinthitis, nor did their offspring
which were reared by their own mothers. By the eighty-sixth
generation all rats in the inbred strain were descendants of
individuals that had been suckled from birth by gray females.
No case of labyrinthitis has appeared in later generations
of this strain. Autopies on about 300 rats of the ninety-sixth
t o the one-hundredth generation, made when the individuals
were a year old, have disclosed infection in the tympanum
and auditory bulIa in some cases, but no involvement of the
Rats in the inbred strain have always been very susceptible
t o pneumonia, and this disease has bcen found t o exist in tlie
great majority of individuals autopsied. The method of
procedure that seemingly has eliminated labyrinthitis from
the strain failed to reduce the iiicidence of pneumonia to
which gray rats are also subject, although the morbidity
rate in them is considerably lower than in albinos. I n rats
of both races pneumonia frequently develops without the involvement of ear infection. This finding strongly suggests,
as Nelson and Gowen ('31) have stated, that the inciting
agents of the two infections are not identical, although they
may be present simultaneously in the same individuals.
Reports on two large colonies of rats, in which the incidence
of middle ear infection was high although the rats appeared
to be in good condition, show that cases of labyrinthitis appeared but rarely in one colony and not at all, apparently, in
the other. Nelson and Gowen ('30) found only four twisters
among the 69% of rats with ear disease in their general stock
coloiiy of albinos. Autopsies of these twisters disclosed
extensive infection in the ear and lesions of the tympanic and
petrous bones. Freudenberger ( ' 3 2 ) does not mention such
individuals in discussing the incidence of middle ear disease
in the different strains of rats he investigated.
It would be a simple and logical explanation f o r the behavior of rats having the ear disorder here designated as
'labyrinthitis' to assume that the organism, or group of organisms, responsible for middle ear disease had penetrated
into the labyrinth and there produced inflammatory conditions in the semicircular canals which cause the discquilibration
shown by afflicted individuals. If this explanation is valid,
then it must be assumed also that many rats have a natural
organ immunity to such organisms which confines their activities to the tympanum. In many old rats whose resistance
to the progress of clisease presumably may have been lessened
by age, pus has been found in the middle ear and in the bulla,
thus indicating that the infection was of long standing. However, there were no bone lesions nor evidence of involvement
of the internal ear in any of these individuals, and none of them
had ever shown the peculiar movements characterizing
tn7ist er s.
The apparent elimination of labyrinthitis from the strain
of inbred albinos by the method of procedure outlined above
and the evident transmission of this disease from infected
albino young to gray females serving as their foster mothers
indicate another possible explanation for the occurrence of
labyrinthitis. It may be that some micro-organism, as yet
unidentified, is the agent producing this particular form of
ear disease. Perhaps this organism is one of the relatively
rare types that have been found among the bacteria commonly
associated with middle ear infection, and it may be the only
one of them sufficiently virulent t o be able to penetrate into
the labyrinth where jt produces a very pernicious kind of
infection. Such an organism, when present in the bacterial
flora of the upper respiratory tract of a female rat, might
readily be transmitted from her mouth to that of an offspring
during the period immediately following parturition when
the young are cleaned and made ready t o suckle. It must be
assumed, however, that there are other ways by which individuals can be infected with this organism, since sporadic
cases of labprinthitis appear at times in strains of rats in
which no form of ear disease is commonly found.
The environmental conditions to which wild gray rats living
in their natural habitat arc subjected are doubtless of importance in determining their susceptibility and availability
to infectious diseases These rats, however, seem to have a
high natural immunity t o many kinds of infection. When
maintained in captivit v under new environmental and nutritive
conditions, they have been found to be relatively free from
tumors, cancer and infections of the genital tract, and more
resistant to middle ear disease and to pneumonia than are
albinos. The rarity of cases of labyrinthitis among captive
gray rats, long rearcid in the same colony with the inbred
albinos in which it was endemic, does not necessarily indicate
that gray rats have a greater natural resistance to this disease
than have albinos. I t may be due merely to the fact that only
a very few individuals ever became hosts to the organism
capable of producing it.
No case of labyrinthitis has been found either in inbred
albinos or in captive grays during the past 4 years. It would
appear, therefore, that the causative agent has been eliminated.
Uriless reinfection occurs, rats i n the colony should be entirely
free from this ailment in the future.
BRADFORD,W. L. 1928 J[ncosus organisin from snppurative lesions of rats
on diets deficient in vitamin A. J. In€. Dis., 1701. 43, pp. 407-414.
CASAMAJOR,L. 1914 Pathological findings in the infectious ear disease of
rodents. Proc. N. Y. Path. SOC.,N. S., vol. 14, pp. 68-72.
AND M. K. HUTTON 1923 Nasal sinusitis
produced by diets deficient in fat-soluble A vitamin. J. Am. Med.
v01. 81, pp. 828-829.
C. B. 1932 The iiicidence of middle-ear infection in the Wistar
albino and the Long-Evans hybrid strain of the Norway rat. Anat.
Rec., rol. 54, pp. 179-184.
H. A., AXD C. C. CONGWN 1924 Suppurative otitis of the albino
rat. Proe. Soe. Esp. Biol. and Med., vol. 22, pp. 150-152.
NELSON,J. R. 1930 a The bacteria of the infected middle ear in adult aiid
young albino rats. J. Inf. a s . , vol. 46, pp. 64-75.
1930 b The reactions of the albino r a t to the intra-oral administration of certain bacteria associated with middle ear disease. J. Exp.
Med., vol. 52, pp. 873-882.
NELSON,J. B., A N D J. W. GOWEN 1930 The incidence of middle ear infection
aiid pneumonia in albino rats at different ages. J. I n f . Dis., vol. 46,
pp. 53-63.
1931 The establishment of an albino rat colony free from middle
ear disease. J. Exp. Med., vol. 54, pp. 629-636.
TURNER,R. G. 1929 Bacteria isolated from infections of the nasal cavities and
middle ear of rats deprived of vitamin A. J. I n f . ])is., vol. 45.
plJ. 208-413.
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method, rat, labyrinthitis, control
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