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Heterochromia of the iris in rabbits belonging to the Dutch breed

Heterochromia of the iris in rabbits belonging to the
Dutch breed.
Kimberly Butler, Beth DeGeorge, Gabriela Dunn, Julie VanGyzen, Michel Gruaz, Arie
van Praag et Esther van Praag
Pigmentation of the iris can present anomalies in Dutch rabbits. It may be sectorial
heterochromia within one iris, complete heterochromia of the iris between one eye
and the other, or ocular albinism with a blue iris in both eyes.
Dutch rabbits, also known as Hollander
or Brabander, belong to a very old breed
and have been represented on antique
etchings of the 16th century already. Its
name refers to the Dutch province of
Holland in the Netherlands. Indeed, it seems
Figure 1: Family of Dutch rabbits with the characteristic bicolor black and white markings and sharp and
even edges between the colored and white areas. Photo: Arie Van Praag June 2016 Page 2 /13
that it originates from this region even
though rabbits showing a coat with Dutch
markings were found more generally in the
Netherlands, in Northern Belgium and in
England. Even so, it was in England that the
Dutch rabbit was selected for its beautiful
coat and its distinctive markings in order to
obtain animals presenting fully symmetric
colored markings. The edges between
colored and white areas should be as even
and sharp as possible (Figures 1, 2).
The colored parts on the body include the
ears, neck, sides of the head (cheeks and
eyes) and the rear end, according to a
straight line running behind the shoulders to
the underneath of the rabbit’s belly (Figures
1, 2). Their size is smaller too.
Hair color in rabbits
Hair growth is accompanied by the
expression of the dark brown eumelanin and
the yellow phaeomelanin pigments. The
presence, absence, or variations in the
combination of these pigments is
determined genetically. The distribution of
pigment density in the hair shaft will affect
the intensity of the color. In long haired
breeds, e.g., the Angora rabbit, the pigment
granules are spread along a greater
distance, causing the color to appear
diluted, whereas in breeds with short hair
such as the Rex rabbit, the granules are
closer to each other and the color becomes
more intense. The absence of any pigments
causes albinism. Albino rabbits typically
have a pale skin, white fur, and pink eyes.
Several hair coloration patterns are found
in rabbits:
- Agouti. It is a multi-band arrangement of
colors along the hair. Along the coloring
of wild rabbits there are several
variations such as brown-grey (Figures
10, 11), or gray as in Chinchilla rabbits.
- Self-color. Each hair has one single color.
The main pigment is eumelanin.
- Multicolor. Areas of hairs with an
eumelanin dominance alternate with
areas of hair with phaeomelanin
dominance or unpigmented hair.
- Albino. Albino rabbits have a very lightly
colored skin, a white fur and pinkish eyes
due to the transparency of the blood
In most rabbit breeds, genes controlling
the color of the fur have undergone
extensive manipulation by breeders in order
to produce breed-specific colors or to
Figure 2 : Young Harlequin or Tri-color Dutch
rabbit with three different colors of fur.
Photo: Arie Van Praag
Figure 3: Young male New-Zealand rabbit with an
entirely white fur and pinkish eyes.
Photo: Arie Van Praag June 2016 Page 3 /13
- Markings, areas with more or less large
areas of white depigmented hair that
form plaques or spots. It can be
differentiated in large areas on the body
as observed on the Dutch rabbit, or
spotted as seen in the spotted rabbit or
the Hotot rabbit.
- Patterning, genes expressing the
eumelanin pigment are sensitive to
temperature and the pigment is only
synthetized under specific
temperature conditions, as seen on
the Himalayan or Russian rabbits, or
the Sable dwarf.
- Shading, it includes a pointed coat
and a partial discoloration over the
body, except limbs, as observed in
the Sable Netherland or Siamese
- Silver, these rabbits are born all
black. A more or less important
depigmentation of the hair tips leads
to the silver effect, as seen on the
Argenté de Champagne.
Genetics of the Dutch coat
Genetics of fur color is complex in
rabbits. Part of the genes deals with
the color of the hair shaft and the
distribution of pigments along the
shaft, or their absence. Other genes
control the distribution of the colored
areas or albino/white on the body.
Finally a gene pool regulates the
intensity of certain colors.
Ten loci determine the appearance
of the fur: A, B, C, D, E, En, Du, Si, V,
and W. Each one may have several
dominant or recessive genes.
The coat of the Dutch rabbit is
determined by the gene "Du" = Dutch.
A homozygous Du/Du rabbit has a
uniform coloration of its fur, without
white hairs or a white nail.
Heterozygous Du/du rabbits have a colored
fur on most parts of their body, with one or
few white markings, e.g., a few white hairs
at the extremity of a limb, a nail, or tip of
the nose. Only homozygous du/du rabbits
will get the typical coat of Dutch rabbits with
white markings/areas of white fur. The
colored fur is gradually invaded by fully
depigmented hairs on more or less
extensive areas of the body. These white
Figure 4: Young male Dutch rabbits showing the
classical white and black markings. Breeders
have introduces other color variations such as
chocolate. Photos: Arie Van Praag June 2016 Page 4 /13
markings appear on the head, neck, upper
trunk, upper limbs, and evolve
independently from each other.
The expression of the "Du" gene does,
however, not explain the variation in the
degree of white marking on the body of
Dutch rabbits, neither the appearance of
newborn with Dutch marking in breeds
whose ancestors are Dutch rabbits. This is,
for instance, observed in litters of the Hotot
rabbit, a "black rabbit with a huge white
marking covering the whole body" except
around the eyes (Figure 5 A, B). There is
usually one or more newborn with an
incomplete marking of the coat. Sometimes
one descendant presents an almost perfect
“Dutch coat” (Figure 5 B).
Nowadays, it is suggested that the Dutch
rabbit as well as breeds selected from the
former carry the dominant "Hol" gene and
many modifying polygenes or “modifiers”
that influence the white marking and,
consequently, the color of the eyes. The
effect of one single polygene has little effect.
It is the sum of polygenes that will
greatly influence the degree of white
marking on the body of the animal
and eye color.
Consequently, it is interesting to
note how genetics leads to numerous
differences in coat and eye color. The
expression of some polygenes leads to
the presence of a few white hairs in
the fur. All intermediaries are
possible, with sporadic cases of
rabbits with blue eyes. The ultimate
stage of white marking is a rabbit with
white fur and blue eyes.
Dutch with blue eyes
The iris is a component of the uveal
tissue of the eye, which acts as a
diaphragm of the eye. Its anterior part
also determines the color to eyes.
The color of the iris, such as we
perceive it, depends on three factors:
- Density of cells producing the
melanin pigment, the melanocytes.
- Density of melanin pigments in the
anterior layer and posterior
epithelium of the iris.
- Density and structure of the
collagen fibers in the anterior layer
and the stroma of the iris.
The density of pigmented cells and
Figure 5: A: Young Hotot rabbits of a same nest,
presenting varying degrees of white marking of
their coat. B: Hotot rabbit referred to as a
wrong Dutch as he presents the typical marking
of the Dutch breed. Photos : Michel Gruaz June 2016 Page 5 /13
melanin pigment varies greatly
in brown or blue irises, less
dense in the latter. The
distribution of pigment cells
within the iris is also different.
In a blue iris, the melanin
pigment is mainly found in the
posterior epithelium, a bit in the
stroma while the anterior layers
have none and are translucent.
The blue or brown color of
the iris is also determined by
the refractive index of light in
the iris, compared to the
surrounding environment. In
the case of blue eyes, light is
little absorbed. Light waves are
reflected to the outside
environment or scatter
throughout the structures of the
eye. The structure of the
anterior layer of the iris and the
absence of melanin pigment
favor the passage of short blue
waves, which allows:
- Transmission of light waves
deeper into the eye, to the
pigmented cells of the
posterior epithelium.
- Diffusion through reflection
of an intense blue light.
The microscopic size of the
different structures of the iris
causes, in addition, a greater
diffusion of short-wave light
(blue) than long-wave light
(red). The iris color is thus
perceived as blue.
When pigmented cells are
present in the anterior layer and
posterior epithelium of the iris,
part of the light is absorbed.
The ratio of the reflected and
scattered light results in the
Figure 6: Dutch rabbit with a different pigmentation within the
same iris. Photos: Kimberly Butler June 2016 Page 6 /13
gray, light brown or dark brown
colors of the iris.
In the case of an iris with
sectoral color variations,
differences in blue and brown
colors are caused by variations
in the size of the different
structures of the iris and/or
changes in the density of
pigmentation between the blue
and brown parts of the iris.
In albino rabbits, the
absence of melanin pigments in
the anterior layer and posterior
iris epithelium allows a full
penetration of light without it
being absorbed. Therefore the
color of the iris of the eye is
pink to purplish. These rabbits
are usually photophobic.
In conclusion, rabbits with a
colored coat have brown or
gray eyes while those with a
very white fur or albino have
light blue or pinkish eye irises.
Dutch rabbits can, however,
sometimes, be born with blue
irises in both eyes, a difference
of color within the same iris or
a difference of color of the iris
of one eye compared to the
other (Figures 6, 7, 8, 9, and
10). This phenomenon is also
observed in rabbit breeds that
have been selected from very
marked (very white) Dutch
rabbits like the Polish or Vienna
White rabbits, both born with
blue eyes (Figures 13, 14).
Geneticists concluded that
there was a sudden mutation of
the recessive gene with
complete penetrance “v",
which is responsible for the
Figure 7: Rabbits belonging to other breeds may also have a
sectorial heterochromia of the iris. Here a lop rabbit
with a very white fur and a possible spotted origin.
Photos : Julie VanGyzen June 2016 Page 7 /13
Figure 8: Another Dutch rabbit avec small depigmented areas in the irises of both eyes. Photos: Maria-
Gabriella Atzori June 2016 Page 8 /13
Figure 9: Lateral view of a Dutch rabbit with heterochromia between the iris of one eye and the other :
brown and normal on his right side and blue on his left side. Photos : Beth DeGeorge June 2016 Page 9 /13
white fur/blue eyes in homozygous v/v
animals. This model of mutation does,
however, not consider that:
- Dutch rabbits may have one or both blue
eyes (Figures 9, 12).
Figure 10: Rabbits with a different pattern of fur coloration may also be affected by sectorial
heterochromia of the iris. It includes rabbits with the agouti pattern, similar to that of wild
rabbits, but also rabbits belonging to the Chinchilla breed. Photos : Gabriela Dunn June 2016 Page 10 /13
- Breeds that descend from the
Dutch rabbit are the result of a
slow and precise selection from
the Dutch rabbit.
In extreme cases, the following
types were obtained:
- Rabbit with a fully white coat and
preservation of the pigmentation
of the iris, as observed in Hotot
rabbits (Figure 5).
- Rabbits with an entirely white and
depigmentation of the iris, or
“white with blue eyes” like the
Vienna White rabbit or the Polish
dwarf rabbit (Figures 13, 14).
There is, thus, a correlation
between the degree of white
marking of the coat and the
appearance of blue eyes in rabbit
belonging to the Dutch breed.
Various hypotheses have been
proposed. The most likely one
remains that suggested by Searle in
1968: the existence of a recessive
“du” gene is accompanied by a
certain number of polygenes
modifying the marking that are
expressed under certain conditions
Heterochromia of the iris
Heterochromia is defined as
variations of color within areas of a
same iris (sectorial heterochromia or
heterochromia iridum) (Figures 6, 7,
8, 10, 11) or a difference of color of
the iris of one eye, compared to the
other eye (heterochromia iridis)
(Figure 9).
In the Dutch rabbit, the observed
types of iris heterochromia have no
clinical importance and do not seem
to be associated to other ocular
anomalies. These include a
Figure 11 : Hétérochromie de l’iris des deux yeux chez un bélier
au pelage agouti. Photos : Nancy Ainsworth June 2016 Page 11 /13
hypoplasia of the iris, a colobome of the iris,
or a displacement of the central position of
the pupil (corectopia). The latter has been
observed in a Vienna White rabbit (Figure
A higher incidence of neurological issues
such as epileptic crisis/seizures has been
observed in white rabbits with blue eyes
that were selected from the Dutch rabbit
(Figures 13, 14). Causes are idiopathic, but
visual or auditory stimuli may become
triggering factors. Those attacks last a few
minutes and present different phases.
Iris heterochromia is also observed in
other rabbit breeds, in particular Chinchilla
or Hotot rabbits. These rabbits often have a
white nail or few white hairs. This anomaly
can also be observed in lop rabbits with a
very white fur (Figure 7).
In cats and few dog breeds, there is an
association between blue eyes and
congenital deafness. This association could
not be established in Dutch rabbits and
rabbits with white fur and blue eyes.
Histology of blue eyes
Histological analyses of blue eye show
that there is a depigmentation of the
mesodermal sheet of the iris, while the
anterior sheets that developed from the
ectoderm are pigmented. In a 6 months old
rabbit with Dutch markings and
heterochrome eyes, the blue eye showed
hypochromia on the front part of the back of
the eye (fundus). It is accompanied by a
reduced pigmentation in the retinal
epithelium and the choroid, in comparison
with the normal pigmented brown eye. A
Figure 12: Young Dutch rabbit with a reduced pigmentation of both eyes, with blue brilliant irises.
Photo: Michel Gruaz June 2016 Page 12 /13
decrease of the amount of pigmented cells
was, however observed in the stroma of the
iris in both eyes.
Many thanks to Tal Saarony (USA), to Janet
Geren (USA) and to a person who wishes to
Figure 13: Displacement of the central position of the pupil (corectopia) in a Vienna white rabbit, a
breed that has been selected from the Dutch rabbit. Photo: Michel Gruaz
Figure 14: Rabbits with a white fur, light colored skin and blue eyes are sensitive to visual and
auditory stimuli. They can lead to seizures. Here a dwarf rabbit. Photos: Arie van Praag June 2016 Page 13 /13
remain anonymous for his help to find rabbits
with heterochrome eyes.
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Every donation, no matter what the size, is appreciated and will aid in
the continuing research of medical care and health of rabbits.
Thank you
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
Eye colour is one of the most important characteristics in determining facial appearance. In this paper I shall discuss the anatomy and genetics of normal eye colour, together with a wide and diverse range of conditions that may produce an alteration in normal iris pigmentation or form.
• Heterochromia was observed in a six-month-old Dutch pigmented rabbit and the rabbit was examined for general and eye anomalies. The rabbit showed a blue eye with fundus hypochromia on the right and a brown eye with partial fundus hypochromia on the left. White fur (white forelock) was present, but deafness was not apparent although no objective audiologic examination was performed. Histology studies of both eyes revealed that significantly fewer pigment cells in iris stroma and less pigmentation in retinal pigment epithelium and choroid in the right eye than in the left eye.
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