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Genetic Welfare Problems of Companion Animals
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Quarter Horse
Hereditary Equine Regional Dermal Asthenia
Related terms: HERDA; hyperelastosis cutis
Related conditions: Ehlers Danlos syndrome
Outline:
Hereditary equine regional asthenia is a degenerative skin disease affecting Quarter horses caused by an abnormality of collagen structure. It is an autosomal recessive disorder, characterised by fragile, thin and loose skin. The clinical severity of the condition can range from mild, with loose, hyper-extensible skin, to severe with spontaneous skin sloughing and scarring. Tears in the skin can be painful and cause irritation. The tensile properties of the eyes, tendons, ligaments and blood vessels may also be affected by the condition. Corneal abnormalities are common in affected horses, with increased corneal thickness, tear production and corneal ulceration. Clinical signs usually appear at the average age of 1.5 years, and may be more noticeable when the horse is ridden. Horses with the condition are often euthanized.
The condition affects both males and females and is recessively inherited in American Quarter horses.
Summary of Information
(for more information click on the links below)
1. Brief description
Hereditary equine regional asthenia is a disorder of the connective tissue characterised by fragile, elastic and loose skin. The underlying defect is that of an abnormality of collagen structure. Collagen is the main structural protein in various connective tissues of the body, including the skin, where it provides strength, elasticity and durability. Normal collagen allows tissue to be stretched but resists over-stretching and helps the tissue return to its normal shape. In horses affected by hereditary equine regional asthenia, there is a reduced density of collagen fibres creating a loose arrangement in the deep dermis of the skin. Affected animals have skin that is loose and does not easily return to its original position, leaving a tented appearance when pinched. The clinical severity of the condition can range from mild, with loose, hyper-extensible skin, to severe with spontaneous skin sloughing and scarring. The skin is thin and prone to tearing, and lesions and scarring are common. Ulcers, thickened masses of skin, and/or swellings may also develop.
The collagen abnormalities of skin thinning and reduced skin strength are found in skin from all areas of the body, but more pronounced reductions in skin strength and larger lesions tend to occur along the back of the affected horse compared to the forelimb or abdominal areas. This may be due to increased susceptibility to trauma and pressure in this area in horses (eg from riding), and/or the effect on collagen of regular exposure to ultraviolet light.
Collagen abnormalities are not limited to the skin and the tensile properties of the eyes, tendons, ligaments and blood vessels may also be affected by the condition, and could be further weakened or damaged by repeated and intense exercise. Corneal abnormalities are common in affected horses with increased corneal thickness, tear production and corneal ulceration.
2. Intensity of welfare impact
The severity of clinical signs seen in affected horses ranges from mild - with no noticeable lesions - to severe, with skin sloughing, open wounds and scarring. Even those horses only mildly affected, still show loose, hyper-extensive skin and, when ridden, this can cause pain and discomfort.
Skin tears and bruising are common, especially in areas that are readily subjected to trauma, and these can be painful and cause irritation. The skin may be hypersensitive, and affected horses may experience discomfort or pain when the skin is touched. Horses with corneal ulcers may experience significant pain and loss of vision.
3. Duration of welfare impact
Clinical signs of equine regional dermal asthenia usually appear at approximately 1.5 years of age, and may be particularly noticeable if the horse is regularly ridden as skin lesions may develop under the saddle. Although affected horses can live a normal lifespan, horses with the condition are often euthanased because they are unable to be ridden, are inappropriate for future breeding and the cost of keeping is high for owners and breeders.
4. Number of animals affected
Both males and females can be affected by the condition. The condition has been reported in several countries, including the United States, Germany, Brazil, United Kingdom and Austria but the prevalence of homozygous affected horses - which carry two copies of the defective gene - is not well reported, and this may be because they are euthanased at the onset of clinical signs.
The frequency of heterozygous carriers of the genetic mutation (ie those horses that carry only one copy of the defective gene and are unaffected but may produce offspring that are affected or carriers) in American Quarter horses in the USA was estimated to be 3.5% but was higher in specific elite performance groups such as cutting and cow horses.
5. Diagnosis
Skin extensibility can be tested using an index based on measuring skin characteristics (vertical height of the skin fold ÷ body length × 100). The skin structure can be examined histopathologically, to identify abnormal changes in the structure and amount of collagen in the skin. Horses can be definitively diagnosed using a DNA test.
6. Genetic
Hereditary equine regional dermal asthenia is an autosomal recessive trait in Quarter horses. This means that the condition can affect both males and females, and that horses require two copies of the genetic mutation responsible for the condition (ie homozygous), one from each parent, in order to be affected. Horses that have one copy of the gene mutation, from one parent, are heterozygous carriers; these horses do not have the condition but carry the genetic mutation and have the potential to pass the mutation onto their offspring. The mating of two heterozygous horses will result in a 25% chance of the offspring being homozygous affected with equine regional dermal asthenia, whilst 50% will be heterozygous carriers for the condition and a further 25% will be clear of the genetic mutation (normal).
The disorder is caused by a missense mutation in the gene that encodes the formation of the collagen. The mutation delays collagen folding and secretion, leading to altered collagen organisation.
7. How do you know if an animal is a carrier or likely to become affected?
Hereditary equine regional dermal asthenia particularly affects American Quarter horses that are descended from a specific prolific stallion called Poco Bueno, foaled in 1944.
A simple DNA test is available to diagnose hereditary equine regional dermal asthenia. The test requires mane or tail hairs with visible roots, and can identify homozygous affected horses, heterozygous carriers and unaffected (wild-type) horses.
8. Methods and prospects for elimination of the problem
Heterozygous carriers are often highly successful in the show ring and have been popular breeding animals, and therefore the frequency of carriers is increasing.
Genetic screening for this condition is recommended for potential breeding Quarter horses or horses with Quarter horse lineage. Breeding of two carriers should be avoided since it is likely to produce 25% homozygous affected horses and 50% heterozygous carriers amongst their offspring.
For further details about this condition, please click on the following:
(these link to items down this page)
- Clinical and pathological effects
- Intensity of welfare impact
- Duration of welfare impact
- Number of animals affected
- Diagnosis
- Genetics
- How do you know if an animal is a carrier or likely to become affected?
- Methods and prospects for elimination of the problem
- Acknowledgements
- References
1. Clinical and pathological effects
Hereditary equine regional asthenia is a form of Ehlers-danlos syndrome (which occurs in humans and a variety of other species, including dogs and cats). It is a disorder of the connective tissue characterised by fragile, stretchy and loose skin (Rashmir-Raven & Spier 2015). The underlying defect is in an enzyme important in the formation of collagen and this results in an abnormality of collagen structure. Collagen is the main structural protein in various connective tissues of the body, including the skin, where it provides strength, elasticity and durability. In animals with normal collagen, collagen allows tissue to be stretched but resists over-stretching and helps the tissue to return to its normal shape.
Collagen in the skin is made up of elongated fibrils that lie parallel to the skin’s surface. These fibrils are formed through the following process. Initially, the pre-cursor for collagen, procollagen, principally made up of the amino acids glycine and proline, is formed inside cells. When procollagen leaves the cell and enters the extracellular space outside, it is trimmed by the enzyme collagenase, and a single collagen fibre is formed (tropocollagen). Multiple tropocollagen molecules then come together to form collagen fibrils via cross-linking and these may be attached to cell membranes.
In horses affected by hereditary equine regional asthenia, there is a reduced density of collagen fibres creating a loose arrangement in the deep dermis of the skin. The clinical severity of the condition can range in affected animals from mild - with loose, hyper-extensible skin - to severe with spontaneous skin sloughing and scarring. Atrophic scars caused by the collagen disruption are common (Badial et al 2014a); these are scars in which the surface of the skin is depressed or sunken. Areas of skin thickening (tumour-like masses) have been observed in affected animals surrounding hyperextensible areas such as on the back (Badial et al 2014a). Swellings of clear serous fluid (seromas) and/or blood haematomas may be seen, and are caused by rupturing of blood vessels in the skin. Ulcers (open wounds) may also be observed, but these usually heal quickly and are less common than scarring and lesions (Badial et al 2014a).
The skin of affected horses is notably thinner than that of unaffected horses; with an average skin thickness of 3.47mm compared to 5.03mm in unaffected horses (Badial et al 2014a), and this decrease in skin thickness is more prominent in dorsal areas and trunk regions.
Affected animals have skin that is loose and does not easily return to its original position, producing a prolonged tented appearance when pinched. The tensile strength of affected horses’ skin is two to five times less than that of skin in healthy horses. The characteristic altered biochemical properties and abnormal collagen synthesis associated with the condition has been found in skin from all areas of the body in affected animals, but with regional differences in tensile strength and presence of skin lesions. Reduced skin strength and increased lesions have been more commonly observed along the back compared to the forelimb or abdomen (Bowser et al 2014, Badial et al 2014a). This may be because skin on the dorsal area is more susceptible to trauma and pressure, eg when the horse is ridden. It is also possible that exposure to ultraviolet light interacts with the abnormal collagen fibres and contributes to the pattern of lesions seen along the dorsal areas (Badial et al 2014a).
Collagen is essential for the structure of the eyes, tendons, ligaments and blood vessels and the tensile properties of these may also be affected in horses with hereditary equine regional asthenia, with greater extensibility and lower tensile strength than normal. Vascular abnormalities are not observed in affected horses, because the reduced strength of major blood vessels is not sufficient for damage to occur at normal physiological vascular pressures (Bowser et al 2014). However, it is possible that damage to these weakened vessels could occur through repeated and intense exercise. A study of 28 homozygous affected horses over 4 years (ie carrying two copies of the defective gene) found abnormal collagen fibril arrangement and decreased corneal thickness, an increase in tear production and an increased incidence of corneal ulceration compared to normal horses (Mochal et al 2010).
2. Intensity of welfare impact
The severity of clinical signs seen in affected horses ranges from mild – with no noticeable lesions - to severe, with skin sloughing, open wounds and scarring. Even those horses only mildly affected still show loose, hyper-extensive skin and, when ridden, this can cause pain and discomfort.
The skin of affected horses is thin and loose, and skin tears and bruising are common, especially in areas that are readily subjected to trauma such as the back, ears, head and legs. The tears can be painful and cause irritation, and horses may rub these areas on surfaces, causing further irritation and damage. The skin may be hypersensitive, and affected horses may experience discomfort or pain when the skin is touched, and this may be seen especially along the dorsal areas (withers to croup; Badial et al 2014a). Horses with corneal ulcers may experience significant pain and loss of vision.
There may be environmental factors that influence the severity of the condition; cool weather and the use of UV light protective sheets appear to help reduce the more severe clinical signs associated with the condition (Rashmir-Raven 2013)
3. Duration of welfare impact
Clinical signs of equine regional dermal asthenia usually appear at the average age of 1.5 years (Rashmir-Raven et al 2004; Tryon 2005, 2007, White 2007), and may be particularly noticeable if the horse is regularly ridden as skin lesions may develop under the saddle. There is no curative treatment for equine regional dermal asthenia, and lesions can be treated to minimise infection. Affected horses can live a normal lifespan, but are at risk of frequent skin tears and injury due to skin fragility. However, horses with the condition are often euthanased because they are unable to be ridden, are inappropriate for future breeding and the cost of keeping is high for owners and breeders.
4. Number of animals affected
Both males and females can be affected by the condition. It appears that intact males are most at risk of being severely affected although the research is not conclusive. It may be that stallions behave in ways more likely to cause trauma to their skin, or that they are monitored more closely for health conditions (Rashmir-Raven 2013).
The condition has been reported in several countries, including the United States, Germany, Brazil, United Kingdom and Austria but the prevalence of homozygous affected horses- which carry two copies of the defective gene - is not well reported, and this may be because they are euthanased at the onset of clinical signs. The frequency of heterozygous carriers of the genetic mutation in American Quarter horses in the USA (ie those horses that carry only one copy of the defective gene and are unaffected but may produce offspring that are affected or carriers) was estimated to be 3.5% (Tryon et al 2009), with previous estimates ranging from 1.8% to 6.5% (Tryon et al 2005). In a recent study of 690 American Quarter horses in Brazil, 40 horses (5.8%) were identified as heterozygous carriers of the genetic mutation responsible for this condition (Badial et al 2014b).
The frequency of heterozygous carriers is higher for Quarter horses used in specific performance disciplines. In the USA, the frequency of heterozygous carriers was 2.3% in elite cutting horses (horses that separate cattle from a herd), 12.8% in Western pleasure horses (style competition horses) and 11.5% in working cow horses (horses that work a single cow in an arena), compared to 3.5% in American Quarter horses overall (Tryon et al 2009). In Brazil, the frequency of carriers was higher for horses used in reigning (a form of dressage riding; 21 carriers in 215; 9.8%) and cutting (17 carriers of 226 horses; 7.5%) compared to barrel racing (a rodeo event) and other racing disciplines (percentages less than 1%; Badial et al 2014b).
5. Diagnosis
Skin extensibility can be tested using an index based on measuring characteristics of the skin (vertical height of the skin fold ÷ body length × 100).
The structure of skin can be examined histopathologically, to identify abnormal changes in the structure and amount of collagen in the skin (Grady et al 2009). Horses can be definitively diagnosed using a DNA test (see below).
6. Genetics
Hereditary equine regional dermal asthenia is an autosomal recessive trait in Quarter horses. This means that the condition can affect both males and females, and that horses require two copies of the genetic mutation responsible for the condition (ie homozygous), one from each parent, in order to be affected. Horses that have one copy of the gene mutation, from one parent, are heterozygous carriers; these horses do not have the condition but carry the genetic mutation and have the potential to pass the mutation onto their offspring. The mating of two heterozygous horses will result in a 25% chance of the offspring being homozygous affected with equine regional dermal asthenia, whilst 50% will be heterozygous carriers for the condition and a further 25% will be clear of the genetic mutation (normal).
The disorder is caused by a missense mutation of the equine peptidylprolyl isomerase B (PPIB) gene, which is associated with the protein folding of collagens (Ishikawa et al 2012). The gene encodes for cyclophilin B (CYPB) – a member of the peptidyl-prolyl cis-trans isomerase family of proteins, which catalyse prolyl-containing bonds in procollagen to the trans configurations, required to form the triple-helical collagen molecule. CYPB has critical functions in procollagen trafficking, processing and chain association. The mutation does not alter prolyl isomerisation activity but delays collagen folding and secretion, which has the consequence of altering collagen organisation (Tryon et al 2007).
7. How do you know if an animal is a carrier or likely to become affected?
Hereditary equine regional dermal asthenia particularly affects American Quarter horses that are descended from a specific stallion called Poco Bueno – he was foaled in 1944 and was prolific, siring 405 American Quarter first-generation foals (Rashmir-Raven & Spier 2015). The first three generations from Poco Beuno alone are likely to have produced approximately 500 horses carrying the gene mutation. According to an American Quarter Horse Association's registrar as of 2006, there were over 1.7 million Quarter Horses, which trace back to Poco Bueno (Gary Griffith, Registrar, American Quarter Horse Association; Rashmir-Raven & Spier 2015).
A simple DNA test is available to diagnose hereditary equine regional dermal asthenia. The test requires mane or tail hairs with visible roots, and can identify homozygous affected horses, heterozygous carriers and unaffected (wild-type) horses.
8. Methods and prospects for elimination of the problem
Heterozygous carriers are often highly successful in the show ring and have been popular breeding animals (Rashmir-Raven & Spier 2015), and therefore the frequency of carriers is increasing.
Genetic screening for this condition is recommended for potential breeding Quarter horses or horses with Quarter horse lineage. Breeding of two carriers should be avoided since it is likely to produce 25% homozygous affected horses and 50% heterozygous carriers amongst their offspring.
The American Quarter Horse Association requires breeding stallions to be tested for the gene mutation as a part of their registration process.
9. Acknowledgements
UFAW thanks Dr Emma Buckland (BSc PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc MSc PhD MRCVS) for their work in compiling this section.
10. References
Häggström, Mikael (2014) Medical gallery of Mikael Häggström. Wikiversity Journal of Medicine 1 (2). DOI: 10.15347/WJM/204.008. ISSN 20018762
Tryon RC, Penedo MCT, McCue ME, Valberg SJ, Mickelson JR, Famula TR, Wagner ML, Jackson M, Hamilton MJ, Nooteboom S and Bannasch DL (2009) Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses.. Journal of the American Veterinary Medical Association 234: 120–5
Valberg SJSJ, Ward TLTL, Rush B, Kinde H, Hiraragi H, Nahey D, Fyfe J and Mickelson JRJR (2001) Glycogen branching enzyme deficiency in quarter horse foals.. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 15: 572–80
Wagner ML, Valberg SJ, Ames EG, Bauer MM., Wiseman JA., Penedo MCT., Kinde H., Abbitt B. and Mickelson JR (2006) Allele Frequency and Likely Impact of the Glycogen Branching Enzyme Deficiency Gene in Quarter Horse and Paint Horse Populations. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 20: 1207–1211
Ward TL, Valberg SJ, Adelson DL, Abbey C a, Binns MM and Mickelson JR (2004) Glycogen branching enzyme (GBE1) mutation causing equine glycogen storage disease IV.. Mammalian genome : official journal of the International Mammalian Genome Society 15: 570–577
Ward TL, Valberg SJ, Lear TL, Guérin G, Milenkovic D, Swinburne JE, Binns MM, Raudsepp T, Skow L, Chowdhary BP and Mickelson JR (2003) Genetic mapping of GBE1 and its association with glycogen storage disease IV in American Quarter horses. Cytogenetic and Genome Research 102: 201–206
© UFAW 2016
Credit for main photo above:
By Psihopat (Own work) [CC-BY-SA-3.0 | (http://creativecommons.org/licenses/by-sa/3.0) or GFDL(http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons
