Hearing Research 115 (1998) 101^112

A model for prelingual deafness, the congenitally deaf white cat ^

population statistics and degenerative changes
Silvia Heid, Rainer Hartmann, Rainer Klinke *
Physiologisches Institut III, Klinikum der J.W. Goethe-Universitaët, Theodor-Stern-Kai 7, D-60590 Frankfurt/M, Germany

Received 16 April 1997; revised 29 September 1997; accepted 8 October 1997

Abstract

Cochlear implantation in congenitally deaf children leads to electrical stimulation of an entirely naive central auditory system. In
this case, processes of central auditory maturation are induced by the electric stimuli. For the study of these processes the deaf white
cat (DWC) appears to be an appropriate model. However, a knowledge of the basic data of these animals is necessary before such a
model may be used. This paper presents these data and is one of a series of publications concerning congenital deafness in children
and cochlear implantation. In our strain 72% of the animals are totally deaf as judged by the absence of any brain stem evoked
potentials at click intensities up to 120 dB SPL peak equivalent. Primarily, there is a degeneration of the entire organ of Corti during
the first postnatal weeks. An absence of acoustically evoked brain stem responses in the early postnatal weeks shows that DWCs
probably never have any hearing experience. Months after the degeneration of the organ of Corti, the spiral ganglion starts to
degenerate from the midportion of the cochlea. However, even in adult cats (2 years), a sufficient number of functionally intact
auditory afferents remain, which are suitable for electrical cochlear stimulation. z 1998 Elsevier Science B.V.

Key words: Congenital deafness; Organ of Corti ; Auditory nerve; Spiral ganglion; Degeneration; Cat; Hearing de¢cit;
Waardenburg

1. Introduction for prelingual deafness and its treatment with cochlear

Cochlear implantation in congenitally deaf children
(Langman et al., 1996) leads to electrical stimulation of
a naive central auditory system. The cerebral structures
concerned have never received sound evoked input. Ma-
turation processes based on auditory experience cannot
therefore have taken place. Electrical stimulation of the
cochlea in these children replaces a peripheral acoustic
input to some extent and apparently triggers matura-
tion processes as the children acquire language compe-
tence. Congenitally deaf animals may provide an ad-
equate model to study functional changes in the
central nervous system induced by these electrical stim-
uli. Chronic electrical stimulation has been shown to be
possible in such animals (Klinke et al., 1997).
If the deaf white cat (DWC) is to be used as a model
* Corresponding author. Tel.: +49 (69) 6301 6976;
Fax: +49 (69) 6301 6987; E-mail: klinke@em.uni-frankfurt.de
implants (see e.g. Hartmann et al., 1997a,b; Heid et al.,
1996, 1997), the hearing de¢cits and morphological
changes should be documented. The type of degenera-
tion, its time course and the population statistics of our
animals provide important data for this model.
Several deaf strains in various species have been re-
ported in the literature, e.g. dog (Rawitz, 1896;
Alexander and Tandler, 1905 ; Mitchell, 1935; Sorsby
and Davey, 1954 ; Suga and Hattler, 1970), mouse (van
Lennep, 1910 ; Gruëneburg et al., 1940 ; Deol, 1970;
Bock and Steel, 1983 ; Brown and Steel, 1994; Steel,
1995). Although these ¢ndings in di¡erent species may
bear relevance to the DWC, we wish to con¢ne our-
selves here to the cat literature. Deaf white cats
(DWCs) with blue eyes were ¢rst reported by Bree
(1828). The ¢rst detailed histological examinations of
these animals were provided by Alexander (1900) and
Alexander and Tandler (1905). Cats of this type were
bred ¢rst by Whiting (1918), who concluded that the

0378-5955 / 98 / $19.00 ß 1998 Elsevier Science B.V. All rights reserved

PII S 0 3 7 8 - 5 9 5 5 ( 9 7 ) 0 0 1 8 2 - 2

HEARES 2937 9-1-98

102 S. Heid et al. / Hearing Research 115 (1998) 101^112
defect was a dominant autosomal aberration clearly
di¡erent from albinism. However, deafness in white
cats may not always be the result of the same genetic
defects.
Several reports concerning these animals have been
published (Bosher and Hallpike, 1965; Suga and Hat-
tler, 1970; Bergsma and Brown, 1971; Mair, 1973 ;
West and Harrison, 1973; Rebillard et al., 1976,
1981a,b; Pujol et al., 1977; Elverland et al., 1977 ; El-
verland and Mair, 1980; Schwartz and Higa, 1982; El-
verland, 1984; Delack, 1984; Larsen and Kirchho¡,
1992 ; Saada et al., 1995, 1996). Although the molecular
basis for the hearing problems in DWCs is not known,
in many of these publications it was suggested that the
animals are a feline homologue of the human Waarden-
burg syndrome (Mair, 1973; Bergsma and Brown,
1971 ; West and Harrison, 1973; Rebillard et al.,
1976, 1981a,b; Schwartz and Higa, 1982; Delack,
1984). The gene mutated in these patients is Pax3.
The Pax3 gene is one candidate for deafness in mice
(see e.g. Steel, 1995). Future molecular analysis of Pax3
will have to be carried out in order to clarify this point.
Thus far in our DWCs no major rearrangements of the
Pax3 gene could be detected using Southern blotting
(Balling, personal communication). However, this ¢nd-
ing does not rule out an involvement of Pax3 as the
cause of pathology in DWCs.
Careful anatomical investigations of the DWC have
been published by Bosher and Hallpike (1965) and
Mair (1973). According to Bosher and Hallpike (1965)
the ¢rst degenerative changes in the organ of Corti
could be seen from postnatal day 5: the authors de-
scribed a collapse of the inner tunnel, a degeneration
and subsequent disappearance of the hair cells and a
change in shape and structure of the tectorial mem-
brane which then clings to the inner sulcus. A progres-
sive atrophy of the stria vascularis has also been re-
ported. Reissner's membrane collapses and folds,
initially towards the spiral limbus and then towards
the tectorial membrane and ¢nally covers the basilar
membrane. The degeneration appeared to take place
in all cochlea turns simultaneously.
Mair (1973) similarly investigated DWCs at di¡erent
ages. In his strain he found the ¢rst degenerative
changes at the 8th postnatal day, i.e. an irregular
wavy appearance of Reissner's membrane in the upper
half of the basal turn. Two days later, Reissner's mem-
brane was observed to contact the inner limbus. Ac-
cording to his description, the organ of Corti proper
cannot be distinguished from Corti's organ in normal
cats at this time. He described a degeneration of the
organ of Corti during the subsequent weeks starting
in the upper half of the basal turn and spreading
from there in both basal and apical directions. In his
animals complete degeneration took 1^2 years, the out-
er hair cells disappearing ¢rst. Atrophy of the stria
HEARES 2937 9-1-98
vascularis was also described. The ¢rst degenerative
changes in the spiral ganglion occurred at 10 months
of age. Rebillard et al. (1981b) reported a variable pat-
tern of degeneration in the organ of Corti and in the
spiral ganglion. Schwartz and Higa (1982) found a de-
generation pattern which started basally and processed
in an apical direction. However, Saada et al. (1995)
reported white cats with residual hearing. In spite of
incomplete hearing loss in their animal, the apex was
already degenerated. Apical outer hair cells and even
apical spiral ganglion cells in the upper turn were com-
pletely missing.
Thus di¡erent descriptions of the time course and the
structural changes of the degenerative process are given
in the literature. It is therefore unlikely that the di¡er-
ent stocks of DWCs investigated su¡er from an identi-
cal genetic defect.
If these animals are to be used as a model for con-
genital human deafness, it must be determined whether
the individuals ever experience hearing levels which are
strong enough for behaviorally relevant auditory sensa-
tions. As reported by Brugge et al. (1978), Laukli and
Mair (1982), Walsh et al. (1986) and Burkard et al.
(1996), and summarized in Romand (1992), the ¢rst
indications of high threshold compound action poten-
tials (CAP) in normal cats can be found by the end of
postnatal week 1. CAP properties mature by the end of
postnatal week 3. The data published by Bosher and
Hallpike (1965) indicate that the organ of Corti in
DWCs degenerates during the period in which the nor-
mal cochlea matures. It can therefore be assumed that
the DWCs, at least the individuals without any residual
hearing, never experience useful hearing levels. Our ex-
perimental data support this assumption.
2. Materials and methods
2.1. Animals
To date, a total of 85 white cats have been observed.
Hearing function was measured in all these animals.
Eye color and length of coat were also evaluated. As
these parameters cannot be determined reliably in kit-
tens, only white cats older than 5 months were included
in the population statistics. For statistical analysis the
Yates corrected M2 -test was used (Sachs, 1974).
The morphological data presented are based on six
normal colored adult cats (2^4 years old) and 10 DWCs
of di¡erent ages (3 days to over 5 years) and of both
sexes. Both strains were bred in our animal house. The
colony was started by a gift of one deaf white male and
four white females with residual hearing by Dr. S. Lar-
sen, Louisville, KY. For further breeding it was ensured
that the males were profoundly deaf. Females had to
have at least severe hearing losses but were accepted if
 S. Heid et al. / Hearing Research 115 (1998) 101^112
they were reproductive and looked well after the litter.
The inbreeding program aimed to provide a large num-
ber of deaf subjects. No data are yet available for in-
terbreeding with normal cats.
The morphological comparison with normal cats is
mainly based on six 2 year old DWCs. Furthermore,
there was one male cat more than 5 years old. This cat
was the ¢rst male we received and came into our animal
house as a sexually mature male of unknown age and
was used as a breeding male as long as possible. It is
very likely that this animal was in fact much older than
5 years. In addition there were one 3 month old kitten
and two kittens 5 and 3 days of age used for morphol-
ogy.
2.2. Assessment of deafness
In general, hearing assessment was performed at an
age of 3^6 weeks by means of acoustically evoked brain
stem responses (BAEPs). In two kittens, a longitudinal
study of BAEPs was performed within the period of
postnatal days 10^31. These repeated tests were not
possible in all animals because of the high risk of losing
the litter.
For the test, the kittens were lightly anesthetized
with Rompun (Bayer, Germany; 0.6 mg/kg body
weight) and Ketavet (Parke-Davis, Germany; 15 mg/
kg body weight). Each ear was tested separately. Acous-
tic stimuli were clicks (50 Ws) at levels up to 120 dB SPL
peak equivalent, presented through an earphone (in-
versely driven BpK 1Q condenser microphone). The
sound pressure in the ear canal was monitored by a
1/4Q Sennheiser electret microphone. BAEPs were re-
corded with subcutaneous silver electrodes (vertex-ear-
lobe). The potentials were ampli¢ed (U500 000) and
bandpass-¢ltered in the frequency range of 10 Hz to
10 kHz. 100 responses at a rate of 13/s were averaged
on-line using an Apple MacIntosh II computer and a
National Instruments AD converter. Only DWCs with
negative results in all of these tests (i.e. completely deaf
animals) were used for histological examinations.
If some hearing function was found in the ¢rst test,
further BAEP tests were undertaken after 6 weeks in
order to follow up the progressive loss of hearing.
Most of the animals were used for other electrophys-
iological experiments before histological examination.
In these animals, the deafness was con¢rmed by an
attempt to elicit click-evoked CAPs from a round win-
dow electrode (Ag/AgCl). Single ¢ber recordings from
the auditory nerve were also attempted.
2.3. Histology
Immediately after an overdose of pentobarbital
(Nembutal, Sano¢, Germany) the animals were trans-
cardially perfused. In order to prevent blood clotting,
HEARES 2937 9-1-98
103
0.5 ml of heparin (Liquemin, Ho¡man-La Roche, Ger-
many) was ¢rst injected into the left ventricle. A can-
nula was then introduced into the left ventricle after
having removed the pericardium. A second cannula
was inserted into the right ventricle and served as an
outlet for the perfusion £uids. Then 1 l of 0.1 M phos-
phate bu¡er (pH 7.4) was infused to rinse the circula-
tory system. The subsequently infused 1 l of ¢xative was
a mixture of 2.5% glutaraldehyde and 2.0% formalde-
hyde (both Merck, Germany). After the perfusion the
head was post¢xed overnight at 4³C in the same ¢xa-
tive. Subsequently the petrous bones were removed
from the skull and contrasted in 1% osmium tetroxide
(Serva, Germany) for 2 h. After that the petrous bones
were cut with a dental drill in order to remove as much
bone as possible and thus reduce the time needed for
decalci¢cation. For this step 0.2 M EDTA was used for
2 days. After dehydration in a graded alcohol series and
passing through propylene oxide (Merck, Germany) as
an intermedium the specimens were embedded in epon
(Serva, Germany). Serial midmodiolar sections, 7 Wm
thick, were cut on a microtome and mounted on ge-
latinized slides with a mixture of H2 O and acetone
(10:1) on a hotplate. The sections were additionally
stained with 0.25% toluidine blue. Finally the sec-
tions were rinsed and coverslipped in Depex (Serva,
Germany).
2.4. Evaluation of the morphology
The slides were evaluated under a light microscope
(Olympus BH-2). The following parameters were of
particular interest:
b position and course of Reissner's membrane, de-
gree of tension
b position and structure of the tectorial membrane
b presence and morphology of hair cells and sup-
porting cells
b di¡erentiation between sensory cells and support-
ing cells
b thickness of stria vascularis
b number of spiral ganglion cells in about 40 mid-
modiolar sections
b presence of nerve ¢bers in the spiral lamina
Each half turn (see below) was evaluated separately.
The di¡erent half turns were delineated as follows.
The cochlea including the hook portion was subdivided
into six half turns. The area of the ganglion of the ¢rst
half turn corresponds to ¢bers originating from the
hook portion. In the subsequent half turns, the gan-
glion areas could be clearly separated. The sections of
the ganglion of the 5th and 6th half turns merge and
were therefore evaluated jointly. As the angle of section
can vary slightly in spite of all precautions in the adjust-
ment of the axis of the modiolus, the ganglion may
appear larger with oblique angles of section. To avoid
104 S. Heid et al. / Hearing Research 115 (1998) 101^112

uncertainties caused by such a variation only the cells

within a square 150U150 Wm2 positioned above the
center of the ganglion were counted, rather than the
complete ganglion area. For evaluation the section
was focused through. To avoid double counts, ganglion
cells were only accepted if the nucleus and the nucleolus
were visible. The number of nerve ¢bers within the spi-
ral lamina could not be counted as no transverse sec-
tions were available.
Fig. 1. Click-evoked CAPs recorded from the round window of a
normal cat compared with a trace gained with the identical tech-
nique in a deaf white cat. No response in the latter case even with
3. Results
20 dB higher sound pressure. At 120 dB SPL (deaf cat) the electri-
cal crosstalk produces an artefact in the recording at the time of the
3.1. Assessment of hearing click (0 ms).

In normal animals, the threshold of the BAEP to the

click stimuli used was less than 54 dB SPL peak equiv-
alent. In contrast, no responses could be detected in
deaf individuals of our white cats up to a sound pres- recordings in all animals that were later used in an
sure of 120 dB SPL peak equivalent. These animals acute experiment. In all these cases, no CAPs could
were de¢ned as `deaf'. In white animals with residual be recorded at even 120 dB SPL peak equivalent. In
hearing, di¡erent threshold values were determined single ¢ber recordings from the auditory nerve no
which ranged from near normal hearing in a few ani- sound evoked or spontaneous single ¢ber activities
mals to severe hearing loss (see Table 1). were found. It was thus concluded that hearing assess-
These negative BAEP results were con¢rmed by CAP ment by BAEPs is satisfactory and that no false nega-
tive results were gained. Fig. 1 shows round window
recorded CAPs in a normal cat and an isoelectric re-
Table 1 cording track in a DWC. A clear CAP is seen at 100 dB
Comparison of hearing thresholds in white cats with residual hear- SPL p.e. in the normal cat. The recording in the DWC
ing using click stimuli is isoelectric with a small initial stimulus artefact due to
Cat ID Threshold left ear Threshold right ear the high sound pressure used.
(dB SPL p.e.) (dB SPL p.e.) In two kittens, BAEP recordings were made at post-
200 80 80 natal days 10, 14, 17, 24 and 31. In one of these kittens
300 98 75 no BAEPs could be recorded even at 120 dB SPL. In
400 82 82 the other kitten a BAEP could be evoked with 114 and
9106 65 70
119 dB SPL p.e. at postnatal day 24. Even this high
9107 90 50
9108 82 78 threshold BAEP could not be reproduced on the sub-
9214 70 70 sequent days (Fig. 2). Five other kittens, measured on
9216 71 80 postnatal days 23 and 24, were completely deaf, i.e.
9218 90 deaf there were no BAEPs up to 120 dB SPL p.e.
9224 115 90
9225 90 95
9230 85 110 3.2. Population statistics
9231 50 45
9333 70 80 The associations between deafness or hearing loss
9334 80 deaf and eye color or length of coat are summarized in Table
9446 92 60
2 (85 cats). As can be seen, 72% of the animals were
9448 42 deaf
9459 95 75 completely deaf at the ¢rst hearing test. Only one adult
9460 deaf 72 animal had normal hearing (cat 9231). This animal had
9567 108 100 a long coat and amber eyes. The remaining animals had
9570 deaf 86 di¡erent degrees of hearing loss and showed a tendency
9575 102 62
to further deterioration. However, none of the cats with
9585 deaf 100
9586 55 85 residual hearing became fully deaf (tested up to 1.5
years). As shown by Yates corrected M2 -test a signi¢cant
The numbers give the sound pressure level necessary to evoke a visible
brain stem potential after 100 summations. Animal no. 9231 is the one correlation between deafness and blue eyes exists
with normal hearing. Note that in normal hearing colored cats hear- (K = 5%). The length of coat does not correlate with
ing threshold are below 54 dB SPL peak equivalent. deafness.

HEARES 2937 9-1-98

 S. Heid et al. / Hearing Research 115 (1998) 101^112
Fig. 2. BAEP recordings from two kittens, one normal hearing kitten at postnatal day 27 and one deaf white kitten at postnatal day 24.
3.3. Morphology
3.3.1. Normal cats
The organ of Corti and spiral ganglion of a normal
cat (basal turn) are shown in Fig. 3. The cochlea of a
normal animal is characterized by a tense Reissner's
membrane with no wave-like structure. The tectorial
membrane covers the organ of Corti. Hair cells and
supporting cells can be easily di¡erentiated. The various
types of supporting cells can also be clearly di¡erenti-
ated. The pillar cells form the inner tunnel with its
typical triangular shape. The stria vascularis consists
of multiple layers of cells.
The spiral ganglion is densely packed with neurons
in Rosenthal's canal and many nerve ¢bers can be fol-
lowed into the spiral lamina. Quantitative results are
summarized as histograms in Fig. 4. Independent of
the origin of the sections, 10^11 ganglion cells per
150U150 Wm2 frame are found in a normally hearing
cat.
3.3.2. Two year old DWCs
Six 2 year old DWCs su¡ering from profound deaf-
ness as veri¢ed by absence of BAEPs (and CAPs, if
applicable) were examined. As the largest number of
animals was available in this group, these animals are
described ¢rst. Reissner's membrane is collapsed and
the cochlear duct is absent in these cochleae. It appears
that a cell layer which originally formed Reissner's
membrane is still present and overlies the cells of the
Table 2
Population statistics of the 85 white cats evaluated for this study
Color of eyes
Deaf white cats (n=61)
2 blue eyes
2 amber eyes
1 blue+1 amber eye
total number
White cats with residual hearing (n=23)
2 blue eyes
2 amber eyes
1 blue+1 amber eye
total number
In addition to the hearing-impaired cats listed above, there was one cat with normal hearing, long coat and amber eyes.
105
basilar membrane and the region of the stria (see Fig.
5). Fragments of the tectorial membrane are retracted
towards the spiral limbus. Hair cells cannot be di¡er-
entiated. The cells on the basilar membrane are rela-
tively uniform in appearance. Cells which stain more
intensely are possibly pillar cells. Although they are in
the expected position, their shape is far from being
normal. The stria is much thinner than in normal inner
ears (16 Wm vs. 25 Wm). With the light microscopic
evaluation melanocytes cannot be identi¢ed. There is
complete degeneration of the organ of Corti in six
half turns.
In contrast, changes in the spiral ganglion are not
equally distributed in the six half turns. In general,
there is a reduction in the number of ganglion cells.
90% of the cells have survived in the basal turn com-
pared to the normal cat. In the second half turn 55% of
the cells are preserved. However, only 27% are present
in the third half turn. In the fourth half turn 45% of the
cells can be found. There is no di¡erence between
DWCs and normal animals in the apical half turns.
Thus the loss of ganglion cells is most severe in the
middle of the cochlea (see Fig. 4). It should be men-
tioned that results from left and right hand cochleae in
individual animals were equal.
The number of preserved nerve ¢bers running in the
spiral lamina is also reduced as compared to normal
animals. As mid-modiolar sections were made, no
transverse sections of nerve ¢bers were available for
counting nerve ¢bers (see Section 2).
Coat length
long coat short coat total number
33 ^ 33
15 1 16
12 ^ 12
60 1 61
3 ^ 3
14 2 16
4 ^ 4
21 2 23
HEARES 2937 9-1-98
106 S. Heid et al. / Hearing Research 115 (1998) 101^112

Fig. 3. Organ of Corti and spiral ganglion in the basal turn (osmium tetroxide and toluidine blue stained) in a 2 year old normal cat. Calibra-
tion bars 100 Wm and 50 Wm respectively.

3.3.3. DWC more than 5 years old
Degeneration of the organ of Corti was more severe
than in the 2 year old animals. Possible fragments of
Reissner's membrane were present. The remnants of
the tectorial membrane were similar to those in 2 year
old cats. The supporting cells appeared quite uniform,
there were no longer more heavily stained cells. The
stria was even thinner (12 Wm) than in the 2 year old
DWCs.
In the spiral ganglion a more severe degeneration
than in 2 year old DWCs was seen (see Figs. 4 and
6). Only 20% of the neurons were preserved in the basal
turn. No ganglion cells remained in the second and
third half turns. One surviving cell was found in the
fourth half turn. However, in the ¢fth and sixth half
turns most of the ganglion cells survived as was also
found in the 2 year old animals. Corresponding to the
absence of ganglion cells a lack of nerve ¢bers in the
midportion of the cochlea was found: the spiral lamina
showed no structures. On the other hand, many nerve
¢bers were found in the apex.
3.3.4. DWC of 3 months
At this age, the organ of Corti is already degenerated
over the entire length of the cochlea. The condition of
Reissner's membrane, tectorial membrane, hair cells
and supporting cells resembles those of the 2 year old
DWCs. It is already impossible to di¡erentiate di¡erent
types of supporting cells, with the possible exception of
questionable pillar cells. In contrast, the thickness of
the stria vascularis corresponds to normal cats (23 Wm).
Also, the spiral ganglion is fully preserved in all
turns (Figs. 4 and 6). The nerve ¢bers also appear to
be fully preserved.

HEARES 2937 9-1-98

 S. Heid et al. / Hearing Research 115 (1998) 101^112
Fig. 4. Ganglion cell counts in standardized sections of the spiral
ganglion in normal and deaf cats. Bars represent standard devia-
tion.
3.3.5. Kittens 3 and 5 days of age
These kittens were not mature enough to be tested
for hearing thresholds as there is no hearing in normal
cats of this age either. According to our population
statistics, there is a more than 90% probability of severe
hearing loss or deafness in these kittens.
In the above kittens, the organ of Corti was present.
It was compared to normal cats of this age by reference
to Bosher and Hallpike (1965). The organ of Corti was
not fully mature in our kittens. For example the inner
tunnel was not open yet in the fourth, ¢fth and sixth
half turns. The hair cells were present and had taken a
mature shape. However, the nuclei lay in the center of
the cells and had not yet migrated to the basal part. The
spiral vessel, a blood capillary just below the basilar
membrane, was quite large in diameter in these animals.
The stria cells in the deeper layers had a reticular
shape indicating their immaturity. Reissner's membrane
HEARES 2937 9-1-98
107
was tensely stretched in all turns. There was no wave-
like structure. As expected, the spiral ganglion was
densely packed with neurons. Nerve ¢bers appeared
thicker than in older animals.
4. Discussion
Whether DWCs experience behaviorally relevant
auditory sensations in the early fourth week of life is
the most important point to be discussed here. Remem-
ber, there was one kitten (out of seven), in which in-
dications of BAEPs were found at 114 dB SPL p.e. and
above. Nevertheless, this cat was classi¢ed as deaf in
the subsequent tests. All other kittens monitored at
this time, and classi¢ed as deaf later on, showed no
BAEPs. A few days of hearing experience cannot be
completely ruled out in the deaf kittens, however, as
tests would need to be done every day in the period
around postnatal day 21. This would cause unaccept-
able stress to the animals. However, only one of the
seven kittens tested showed high threshold BAEPs.
Moreover, the sound levels necessary to evoke this re-
sponse are not normally reached in our animal house.
Mean ambient noise levels there were measured in the
range of 60 dB Leq . Only occasional peaks in sound
pressure would be suprathreshold, if at all, and it is
very likely that these would not form biologically mean-
ingful stimuli. Similarly children with severe hearing
loss, e.g. 90 dB and above, seem not to make use of
occasionally occurring high level acoustic stimuli. How-
ever, if these children are equipped with high power
hearing aids in time, they perform quite well (Diller,
1990).
We thus conclude that the DWC is an adequate
model for congenital deafness and that the auditory
system has not received substantial peripheral input
which could trigger input-dependent maturation proc-
esses.
4.1. Population statistics
A higher percentage of deaf individuals (72%) was
found in our strain of DWCs than that given in the
literature. Bosher and Hallpike (1965) found 68%,
Mair (1973) 52%. Both data are based on morpholog-
ical analyses rather than on hearing tests.
Our results con¢rm observations by Bree (1828) and
later investigators that the probability of hearing de¢-
cits is higher in individuals with two blue eyes (Bergsma
and Brown, 1971 ; Mair, 1973). Mair (1973) further
described cases where unilateral deafness was correlated
with a blue eye on the hearing-impaired side, the second
eye being of amber color. Four cats with two di¡erent
eye colors were found in our sample. In two of them on
the deaf side the eye was blue. The remaining animals
108 S. Heid et al. / Hearing Research 115 (1998) 101^112

Fig. 5. Organ of Corti and spiral ganglion in the basal turn (osmium tetroxide and toluidine blue stained) in a 2 year old deaf white cat. Cali-
bration bars 100 Wm and 50 Wm respectively.

had hearing losses in both ears, but were not pro-
foundly deaf (animals 9585, 9586).
As compared to Mair (1973) in our stock more ani-
mals had long coats (96% vs. 36%).
4.2. Comparison of morphological data on DWCs
A number of papers have been published on the
morphology and time course of degeneration of the
organ of Corti and the spiral ganglion in DWCs. The
¢ndings of these papers di¡er and it seems questionable
whether the genes involved in deafness of these animals
were identical.
Many investigators see the DWC as a homologue of
the human Waardenburg syndrome (Bergsma and
Brown, 1971; Mair, 1973; West and Harrison, 1973;
Rebillard et al., 1976, 1981a,b; Schwartz and Higa,
1982 ; Delack, 1984). However, no one has tested this
hypothesis before. Using Southern blotting in our cats,
no major rearrangement of the Pax3 gene could be
detected (Balling, personal communication). However,
this ¢nding does not rule out point mutations. The
variability of data in the literature, however, suggests
that there my be di¡erent types of DWCs. The fact that
in our cats there was one animal with normal hearing,
of which the father was deaf and the mother severely
hard of hearing, indicates that modifying genes seem to
be involved.
The DWCs of our stock are born with an organ of
Corti that appears morphologically intact with an age-
appropriate development. Nevertheless, hearing func-
tion does not develop normally. At 3 months of age
degeneration of Corti's organ is complete in all cochlear
turns. The degeneration of the spiral ganglion is much

HEARES 2937 9-1-98

 S. Heid et al. / Hearing Research 115 (1998) 101^112 109

Fig. 6. Comparison of the spiral ganglion in the basal turn (osmium tetroxide and toluidine blue stained) in deaf white cats. Top: 3 month old
deaf white cat. Bottom: 5 year old deaf white cat. Calibration bars 50 Wm.

slower. No ganglion cell losses are seen at 3 months.
Later degeneration starts in half turn III, which corre-
sponds to the upper part of the basal turn, and pro-
ceeds towards both base and apex. Finally, the ganglion
cells completely disappear in the midportion of the
cochlea, but ganglion cells are found in the hook por-
tion and particularly in the apex even in old animals.
This pattern approaches the description of Bosher
and Hallpike (1965). These authors report that signs
of degeneration are never observed before the ¢fth
day and that the degeneration of the organ of Corti is
¢nished by day 21.
Similarly, our data correspond to those of West and
Harrison (1973) who described the spiral ganglion to be
largely normal in the apical region, whereas substantial
cell losses were reported from the middle and basal
portions.
In contrast, our data di¡er from those of Mair
(1973). In his cases, degeneration started in the upper
part of the basal turn. However, degeneration took up
to 2 years and the outer hair cells disappeared ¢rst.
Even near the end of the second year (22 months) inner
hair cells were present in the basal and apical parts.
Degeneration was by no means complete by day 21 as
described by Bosher and Hallpike (1965). Mair (1973)
also examined the spiral ganglion. In Mair's data, no
alterations could be seen in the spiral ganglion before
the age of 10 months. At 19 months, a clear reduction
in the number of ganglion cells was reported. The loss
was also most severe in the cochlear midportion. In our
animals the degeneration of the organ of Corti is much
faster.
In a recent communication Saada et al. (1995) re-
ported about a white cat with residual hearing in which

HEARES 2937 9-1-98

110 S. Heid et al. / Hearing Research 115 (1998) 101^112
a portion of the basal inner hair cells and ganglion cells
had survived. In this cat no ganglion cells were found
in the apical region. In these authors' completely deaf
white cats the organ of Corti and spiral ganglion
cells were absent in all turns. In our preparations an
apical cochlea devoid of ganglion cells has not been
observed.
A variable pattern of degeneration was reported by
Pujol et al. (1977), Rebillard et al. ( 1976, 1981a,b). In
particular, Rebillard et al. (1981b) reported a cat where
the spiral ganglion was absent in spite of a largely nor-
mal organ of Corti. This combination of results was
never seen in our animals. Surprisingly, Rebillard et
al. (1981a) described a cat with residual hearing where
the organ of Corti was no longer recognizable.
A degeneration proceeding from base to apex was
found by Schwartz and Higa (1982). In their specimens,
the loss of ganglion cells could only be seen after 10
months and was most severe in the basal area. Again,
this is at variance with our ¢ndings. The time course
and pattern of degeneration was uniform in all our
animals.
There are a number of deaf strains in mice where
pigmentation anomalies are associated with inner ear
defects (partly both cochlear and vestibular). However,
indications of vestibular disturbances have never been
observed in our stock. Thus one of the mutants w/wv
(Schrott and Spoendlin, 1987), sl/sld (Schrott et al.,
1990) and mibw /mibw (Motohashi et al., 1994) may be
similar to our DWCs.
4.3. Comparison with experimentally deafened normal
cats
Some investigations use pharmacologically deafened
cats as a model for human deafness. There are similar-
ities and di¡erences in the degeneration of the cochlea
in DWCs and experimentally deafened normal cats.
Leake and Hradek (1988) described the time course of
degeneration in the organ of Corti and spiral ganglion
after neomycin deafening in adult cats. This drug ¢rst
impairs the basal cochlea. With long survival times the
midportion is also impaired. Apically, Corti's organ is
still present but shows structural alterations. The degen-
eration of the spiral ganglion is similar. There is a clear
correlation between survival time and preservation of
the inner ear structures. After 3^4 years only 2^3% of
the ganglion cells survive in all turns. Degeneration is
thus more severe in neomycin-deafened animals than in
our DWCs. More ganglion cells had survived even in
our oldest cat.
In their electron microscopy studies Leake and Hra-
dek (1988) showed that a demyelination of the a¡erent
nerve ¢bers occurs. Myelinated type I neurons trans-
form into unmyelinated type III units which can still
be di¡erentiated from type II neurons. Such a trans-
HEARES 2937 9-1-98
formation was also reported in DWCs by Elverland
and Mair (1980).
In a later study, Leake et al. (1992b) described kit-
tens neonatally deafened with neomycin. There was an
initial loss of organ of Corti and spiral ganglion cells in
the cochlear midportion, similar to that found in our
DWCs.
A similar course of events was reported by Xu et al.
(1993). These authors deafened adult cats with a com-
bination of kanamycin and etacrynic acid. In nine out
of 14 cochleae a complete loss of hair cells in all turns
was found. In the remaining specimens, surviving hair
cells and supporting cells were found in the apex. The
ganglion cells degenerate subsequent to the organ of
Corti, taking years to fully disappear.
The results of electrical cochlear stimulation in ex-
perimentally deafened cats are contradictory. Leake et
al. ( 1992a, 1995) reported that unilateral electrical
stimulation through a cochlear implant leads to a better
survival of ganglion cells compared to the unstimulated
control. Extracochlear stimulation is reported to result
in a 6% higher survival rate of ganglion cells and intra-
cochlear stimulation is reported to lead to a 13% in-
crease. Shepherd et al. (1994), on the other hand, did
not ¢nd signi¢cant di¡erences between stimulated and
non-stimulated cochleae with respect to ganglion cell
survival. Experiments on cochlear implantation in our
DWCs are in progress. It is hypothesized that the DWC
is better suited to studies of early cochlear implantation
because of the better survival of ganglion cells in these
animals.
5. Conclusions
It appears that the DWC is an appropriate model for
the study of central nervous consequences of congenital
hearing disorders. A su¤cient number of animals is
completely deaf from early infancy. If there is some
hearing in these animals at all, thresholds (near 120
dB SPL peak equivalent) are far above ambient sound
levels and the episode of residual hearing is con¢ned to
a time span of a few days around postnatal day 24.
Thus the animals do not receive su¤cient external stim-
uli to develop useful hearing capabilities.
A su¤cient number of a¡erent ¢bers are available in
DWCs and can be stimulated (Hartmann et al., 1997b;
Klinke et al., 1997) to study the e¡ects of early electri-
cal cochlear stimulation. Whether chronic electrical
stimulation reduces the proportion of degenerating af-
ferents, as has been reported in experimentally deafened
animals by Leake et al. ( 1992a,b), remains to be seen.
The larger number of surviving ganglion cells in DWCs
compared to experimentally deafened animals supports
the use of DWCs as a scienti¢c model.
An important caveat is that di¡erent genotypes and
 S. Heid et al. / Hearing Research 115 (1998) 101^112
phenotypes of deafness in DWCs possibly exist. Careful
physiological monitoring of hearing is necessary before
kittens are used for neurophysiological experiments.
Acknowledgments
This work was supported by the Deutsche For-
schungsgemeinschaft (SFB 269). Ms. Natalie Krimmel
is thanked for careful technical assistance.
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