Degenerative Suspensory Ligament Desmitis in horses research by Jaroslava Halper, MD, PhD
We are super excited to help Professor J. Halper in her research for DSLD.
To date we have collected donations to collect samples and identified horses that may be affected.
Please read below about the research;
Degenerative Suspensory Ligament Desmitis in HorsesA Research Synopsis by Jaroslava Halper, MD, PhD
Equine degenerative suspensory ligament desmitis (DSLD) is a chronic painful disorder
affecting primarily, but not only, lower extremities of horses. As a consequence many affected
horses become lame, and some undergo euthanasia due to increasing pain. This disorder is
most likely genetic in nature, however, no gene has been identified as of now.
DSLD was first recognized in Peruvian Pasos. We do know more about the pathogenesis and
pathology of DSLD as the result of research done by us. Our laboratory was the first to find that
DSLD is a systemic disease affecting organs and structures with high content of connective
tissues. This includes not only tendons and ligaments, but also parts of the cardiovascular
system, such as aorta and coronary arteries, in addition to sclerae and skin among others. The
pathological hallmark of DSLD is inappropriate presence of proteoglycans in connective
tissues. The diagnosis of DSLD in living horses relies on physical examination and on
ultrasound of suspensory ligaments of the lower extremities. However, this approach is not
always reliable and accurate. Post mortem findings represent the gold standard, but they come
too late for treatment and management. Our recent data indicate a new and unique way to
develop a reliable diagnostic assay using existing technology.
The nature of skin changes has not been well documented and its significance is unknown.
Most recently, sequencing of RNA samples extracted from DSLD and control skin biopsies was
performed in our lab. The rationale for sequencing skin RNA rather than tendon RNA was
associated with procedural ease and low risk to the patient. Though tendons/ligaments are the
most affected tissues in DSLD, they are not routinely biopsied as this would lead to permanent
tendon/ligament damage in many horses, particularly in horses with DSLD. Skin, on the other
hand, is easily accessible, biopsy wounds heal well and without scarring (even in DSLD). Since
we have re-defined DSLD as a systematic disorder, we hypothesized that differential gene
expression in DSLD would be comparable among different tissues and organs afflicted by
DSLD.
Surprisingly, our results showed markedly increased expression of keratin genes in skin of
horses with DSLD. This was an impetus for our initial studies and for developing this proposal.
We are developing a specific diagnostic assay panel for DSLD. We chose two tissue based
assays, immunohistochemistry and in situ hybridization, to identify select keratins in skin
biopsies. So far, we have concentrated on the expression of keratins 81 and 39, as both were
highly expressed in our RNA sequencing study, and also because antibodies to these two
keratins are commercially available. Keratin 81 is a type II hair keratin, which together with type
I keratins forms hair and nails. Keratin 39 is a I type keratin, a component of cytoskeleton of
epithelial cells, and hair. We have identified both keratins in skin samples during our first runs of
immunohistochemistry and/or in situ hybridization. So far, utilizing polyclonal antibodies, we
have identified both keratins 39 and 81 to be present at higher levels in DSLD skin. We have
performed one run of in situ hybridization of RNAscope set of mRNA for KRT81 with 10
samples. The expression of mRNA for KRT81 was stronger in hair follicles in DSLD skin than in
normal hair follicles. In addition, more hair follicles were stained in DSLD than in control
histological sections.
I would like to emphasize that our approach to this devastating disorder is unique and that our
results rewrote the mantra on DSLD. The development of a diagnostic assay would represent
another major breakthrough in the field and would be greatly appreciated by horse owners and
breeders worldwide. It would contribute greatly to improve well-being and welfare of horses as
early diagnosis would inform proper management and breedin
Relevant publications:
1. Haythorn A, Young A, Stanton J, Zhang J, Mueller POE, Halper J. 2020. Differential gene
expression in skin from horses affected with degenerative suspensory ligament desmitis. 2020.
J Orthopaed Surg Res, 15, 460, DOI: 10.21203/rs.3.rs-41297/v2
2. Young M, Moshood O, Zhang J, Sarbacher CA, Mueller POE, Halper J. 2018. Does BMP2
play a role in the pathogenesis of equine degenerative suspensory ligament desmitis? BMC Res
Notes 11(1):672.
3. Halper J., Mueller P.O.E. 2018. Dystrophic mineralization in DSLD: Clinical commentary.
Equine Vet Edu 30:424-426
4. Halper J, Khan A, Mueller POE. 2011. Degenerative suspensory ligament desmitis – a new
reality. Pak Vet J 31:1-8.
5. Kim B, Yoon JH, Zhang J, Mueller POE, Halper J. 2010. Glycan profiling of a defect in
decorin glycosylation in equine systemic proteoglycan accumulation, a potential model of
progeroid form of Ehlers-Danlos syndrome. Arch Biochem Biophys, 501:221-231.
6. Halper J. Peruvian Paso PLUS. The Gaited Horse, Spring 2007.
7. Halper J, Kim B, Khan A, Yoon JH, Mueller POE. 2006. Degenerative suspensory ligament
desmitis as a systemic disorder characterized by proteoglycan accumulation. Biomed Central
Veterinary Research 2:12.
.
Equine degenerative suspensory ligament desmitis (DSLD) is a chronic painful disorder
affecting primarily, but not only, lower extremities of horses. As a consequence many affected
horses become lame, and some undergo euthanasia due to increasing pain. This disorder is
most likely genetic in nature, however, no gene has been identified as of now.
DSLD was first recognized in Peruvian Pasos. We do know more about the pathogenesis and
pathology of DSLD as the result of research done by us. Our laboratory was the first to find that
DSLD is a systemic disease affecting organs and structures with high content of connective
tissues. This includes not only tendons and ligaments, but also parts of the cardiovascular
system, such as aorta and coronary arteries, in addition to sclerae and skin among others. The
pathological hallmark of DSLD is inappropriate presence of proteoglycans in connective
tissues. The diagnosis of DSLD in living horses relies on physical examination and on
ultrasound of suspensory ligaments of the lower extremities. However, this approach is not
always reliable and accurate. Post mortem findings represent the gold standard, but they come
too late for treatment and management. Our recent data indicate a new and unique way to
develop a reliable diagnostic assay using existing technology.
The nature of skin changes has not been well documented and its significance is unknown.
Most recently, sequencing of RNA samples extracted from DSLD and control skin biopsies was
performed in our lab. The rationale for sequencing skin RNA rather than tendon RNA was
associated with procedural ease and low risk to the patient. Though tendons/ligaments are the
most affected tissues in DSLD, they are not routinely biopsied as this would lead to permanent
tendon/ligament damage in many horses, particularly in horses with DSLD. Skin, on the other
hand, is easily accessible, biopsy wounds heal well and without scarring (even in DSLD). Since
we have re-defined DSLD as a systematic disorder, we hypothesized that differential gene
expression in DSLD would be comparable among different tissues and organs afflicted by
DSLD.
Surprisingly, our results showed markedly increased expression of keratin genes in skin of
horses with DSLD. This was an impetus for our initial studies and for developing this proposal.
We are developing a specific diagnostic assay panel for DSLD. We chose two tissue based
assays, immunohistochemistry and in situ hybridization, to identify select keratins in skin
biopsies. So far, we have concentrated on the expression of keratins 81 and 39, as both were
highly expressed in our RNA sequencing study, and also because antibodies to these two
keratins are commercially available. Keratin 81 is a type II hair keratin, which together with type
I keratins forms hair and nails. Keratin 39 is a I type keratin, a component of cytoskeleton of
epithelial cells, and hair. We have identified both keratins in skin samples during our first runs of
immunohistochemistry and/or in situ hybridization. So far, utilizing polyclonal antibodies, we
have identified both keratins 39 and 81 to be present at higher levels in DSLD skin. We have
performed one run of in situ hybridization of RNAscope set of mRNA for KRT81 with 10
samples. The expression of mRNA for KRT81 was stronger in hair follicles in DSLD skin than in
normal hair follicles. In addition, more hair follicles were stained in DSLD than in control
histological sections.
I would like to emphasize that our approach to this devastating disorder is unique and that our
results rewrote the mantra on DSLD. The development of a diagnostic assay would represent
another major breakthrough in the field and would be greatly appreciated by horse owners and
breeders worldwide. It would contribute greatly to improve well-being and welfare of horses as
early diagnosis would inform proper management and breedin
Relevant publications:
1. Haythorn A, Young A, Stanton J, Zhang J, Mueller POE, Halper J. 2020. Differential gene
expression in skin from horses affected with degenerative suspensory ligament desmitis. 2020.
J Orthopaed Surg Res, 15, 460, DOI: 10.21203/rs.3.rs-41297/v2
2. Young M, Moshood O, Zhang J, Sarbacher CA, Mueller POE, Halper J. 2018. Does BMP2
play a role in the pathogenesis of equine degenerative suspensory ligament desmitis? BMC Res
Notes 11(1):672.
3. Halper J., Mueller P.O.E. 2018. Dystrophic mineralization in DSLD: Clinical commentary.
Equine Vet Edu 30:424-426
4. Halper J, Khan A, Mueller POE. 2011. Degenerative suspensory ligament desmitis – a new
reality. Pak Vet J 31:1-8.
5. Kim B, Yoon JH, Zhang J, Mueller POE, Halper J. 2010. Glycan profiling of a defect in
decorin glycosylation in equine systemic proteoglycan accumulation, a potential model of
progeroid form of Ehlers-Danlos syndrome. Arch Biochem Biophys, 501:221-231.
6. Halper J. Peruvian Paso PLUS. The Gaited Horse, Spring 2007.
7. Halper J, Kim B, Khan A, Yoon JH, Mueller POE. 2006. Degenerative suspensory ligament
desmitis as a systemic disorder characterized by proteoglycan accumulation. Biomed Central
Veterinary Research 2:12.
.