Previously Funded Studies
01547-A: Genetic Analysis of Alopecia X in Pomeranians
Grant Status: Open
Grant Amount: $12,960
Dr. Tosso Leeb, PhD, University of Bern
May 1, 2011 – April 30, 2012
Sponsor(s): American Pomeranian Club, Inc.
Breed(s): Pomeranian
Disease(s): Alopecia
Abstract
LAY ABSTRACT: Alopecia X
occurs most frequently in Pomeranians but has also been
described in several arctic breeds with plush undercoat
such as the Keeshond, , Samoyed, Chow-Chow, and Alaskan
Malamute. It is characterized by hair loss and dark
coloration of the affected skin areas. The disease
typically starts at 6 months to 5 years of age and
predominantly affects the rump of the animals. Alopecia
X has also been termed “growth hormone-responsive
alopecia” and “black skin disease”. Although many
experts believe in a genetic cause for alopecia X, the
exact mode of inheritance is still under discussion.
In previous research projects we and others have tried
to identify known genes involved in hair growth. These
so-called candidate genes were then inspected for
changes between healthy and alopecia X affected dogs.
Unfortunately, so far none of the investigated candidate
genes turned out to be the causative gene for alopecia
X. We now successfully applied a new technique
(genome-wide association study, GWAS) to determine that
a major genetic risk factor is located on a small
portion of a single chromosome. With this application we
would like to completely sequence this region in two
affected and two control Pomeranians. We expect to get a
large list of variants including the causative mutation
from this experiment. As we expect the causative mutation
to be either non-coding or in a previously unknown gene,
it will probably require significant additional efforts
to finally identify the causative mutation itself and
develop genetic testing.
01197-A: Genetic Analysis of Alopecia X in Pomeranians and Keeshonden
Grant Status: Closed
Grant Amount: $12,960
Dr. Tosso Leeb, PhD, University of Bern
March 1, 2009 – February 28, 2010
Sponsor(s): Keeshond Club of America, Pomeranian Charitable Trust
Breed(s): Keeshond, Pomeranian
Disease(s): Alopecia
Project Summary
Alopecia X is an inherited disease in Pomeranians and other breeds with plush undercoat. It leads to hair-loss and sometimes also to a darkening of the underlying skin. Male dogs are much more frequently affected than female dogs, which has led to speculations that a hormonal imbalance might be involved in this disease. However, up to now the cause of alopecia X remains unknown. As the underlying problem has not yet been discovered, we employed a purely genetic approach to localize the mutation in the dog genome. Using SNP chip technology and a so-called genome-wide association study, we were able to show that the mutation causing alopecia X resides on a small segment of chromosome 15. This result is an important advance as there are only ~10 genes in this segment. This means that the other ~20’000 genes in the dog genome are not responsible for alopecia X and need not be further investigated. Unfortunately none of the genes in the associated interval on chromosome 15 has a known involvement in hair growth. Therefore, we will next need to perform a very labor-intensive investigation of all variants in this region to be able to identify the causative mutation for alopecia X.
Publication(s)
Fatima Wingeier (2009)
Alopecia X in Pomeranians – A Genome Wide Association
Analysis. Master Thesis. Faculty of Natural Sciences,
University of Bern.
00812-A: Investigation of the Canine Cathepsin L Gene (CTSL) as a Candidate for Alopecia X in Keeshonden and Pomeranians
Grant Status: Closed
Grant Amount: $12,600
Dr. Tosso Leeb, PhD, University of Bern
December 1, 2006 – May 31, 2007
Sponsor(s): Keeshond Club of America, Pomeranian Charitable Trust
Breed(s): Alaskan Malamute, Chow Chow, Keeshond, Pomeranian, Samoyed
Disease(s): Alopecia
Project Summary
Alopecia X is a noninflammatory, progressive, bilateral symmetric alopecia in dogs. The disease is mainly found in Nordic breeds. The breed predisposition and a strong familial accumulation suggest a hereditary background. We analyzed the cathepsin L2 gene (CTSL2) as a candidate for alopecia X. The comparative sequencing of 14 affected and 18 control animals revealed ten polymorphisms; however, none of these polymorphisms affected the coding sequence. Haplotype analysis did not reveal an association of one particular CTSL2 haplotype with the disease phenotype; therefore, we conclude that the CTSL2 gene is probably not the causative gene for alopecia X.
Publication(s)
– Mausberg, Em, Drogemuller,
C, Dolf, G, Leeb, T, Rufenacht, S and Welle, M (2007)
Evaluation of the CTSL2 Gene as a Candidate Gene
For Alopecia X in Pomeranians and Keeshonden. Animal
Biotechnology. 18, 291 – 6.
– Mausberg, Em, Drogemuller, C, Dolf, G, Rufenacht, S,
Welle, M and Leeb, T (2008) Exclusion of patched homolog
2 (PTCH2) as a candidate gene for alopecia X in
pomeranians and keeshonden. Veterinary Record. 163,
121-3. 10.1136/vr.163.4.121
00695-A: Estrogen Receptor Antagonist and Hair Regrowth
in Dogs with Follicular Arrest (Alopecia X)
Grant Status: Closed
Grant Amount: $9,936
Dr. Linda Frank, DVM, University of Tennessee
December 1, 2005 – November 30, 2006
Sponsor(s): Alaskan Malamute Research Foundation, Inc., American Pomeranian Club, Inc.
Disease(s): Alopecia
Abstract
Follicular arrest (also known
as Alopecia X, adrenal hyperplasia-like syndrome, growth
hormone responsive alopecia, and others) is a common
condition seen in Pomeranians and other “plush-coated”
breeds. While systemic illness is not associated with
this disease, the loss of hair is dramatic and of
concern to the owner. The pathomechanism of the hair
loss is not known, but appears to be related to an
abnormality in the hair follicle?s ability to cycle
properly. Once the hair is in telogen or resting phase
of the hair cycle, new hair growth does not occur.
Recently there has been the recognition of an estrogen
receptor pathway that appears to regulate the transition
of the hair from resting to active growth. We
hypothesize that dogs with follicular arrest have
increased activity of estrogen receptors in hair
follicles preventing the hair follicles from cycling
normal. A potent estrogen receptor blocker has been
developed for treating women with breast cancer. It has
been extensively tested in dogs and has no side effects
except for those related to anti-estrogen activity such
as reduction in fertility. Therefore, we would like to
test the ability of this drug to cause hair regrowth in
Pomeranian dogs with follicular arrest. This will be a
pilot study in which 5 dogs with alopecia will receive
an intramuscular injection of the active drug (fulvestrant)
monthly for 2 months and 5 will receive placebo. The
dogs will be evaluated for hair regrowth in 1 month
intervals. If hair regrowth occurs, the dogs which
received placebo will be offered the active drug. CBC,
chemistry panel, and urinalysis will be monitored prior
to receiving the first injection, and monthly for 2
months.
0002290: Mapping Canine X Chromosome Linked Alopecia
Grant Status: Closed
Grant Amount: $14,415.7
Dr. Gary S. Johnson, DVM PhD, University of Missouri, Columbia
April 16, 2002 – March 31, 2003
Sponsor(s): American Pomeranian Club, Inc., Anonymous, Pomeranian Philanthropists
Breed(s): Alaskan Malamute, Keeshond, Pomeranian
Disease(s): Alopecia
Abstract
Many young Pomeranians develop a luxurious puppy for first hair coat which fails to shed and is not replaced by an adult coat. As the puppy coat ages it breaks off and falls out and can result in a dog that is hairless over much of its body. This disease is sometimes called black skin disease, coat funk or woolly coat. It also occurs in Keeshonden and Alaskan Malamutes. Although females can have the disease, it is much more common in males. This suggests, but does not prove, that the mutation responsible for the disease is on the X chromosome. We propose to determine if a DNA marker from the canine X chromosome associates with the disease. If so, this marker could then be used to distinguish genetically normal puppies from puppies that are likely to develop the disease. This marker could also identify female puppies that will not develop the disease but are likely to pass the disease on to the next generation.
