title: Increased susceptibility of skin from HERDA (Hereditary Equine Regional Dermal Asthenia)-affected horses to bacterial collagenase degradation: a potential contributing factor to the clinical signs of HERDA.
abstract: BACKGROUND
  Hereditary equine regional dermal asthenia (HERDA) is a genetic disorder of collagen resulting in fragile, hyper-extensible skin and ulcerative lesions. The predominance of skin lesions have been shown to occur on the dorsum of HERDA-affected horses. While this has been postulated to be due to increased exposure to sunlight of these areas, the precise pathological mechanism which causes this to occur is unclear.
  
  
  OBJECTIVE
  We hypothesized that an increase in collagenase activity, that has been associated with the exposure of dermal fibroblasts to sunlight, will significantly degrade the material properties of skin from HERDA-affected horses when compared to unaffected controls.
  
  
  METHODS
  Six unaffected and seven HERDA-affected horses, all euthanized for other reasons.
  
  
  METHODS
  Full-thickness skin samples from similar locations on each horse were collected and cut into uniform strips and their material properties (tensile modulus) determined by mechanical testing before (n = 12 samples/horse) or after (n = 12 samples/horse) incubation in bacterial collagenase at 37°C for 6 h. The change in modulus following treatment was then compared between HERDA-affected and unaffected horses using a Student's t-test.
  
  
  RESULTS
  The modulus of skin from HERDA-affected horses decreased significantly more than that from unaffected horses following collagenase treatment (54 ± 7% versus 30 ± 16%, P = 0.004).
  
  
  CONCLUSIONS
  The significant decrease in the modulus of skin from HERDA-affected horses following collagenase exposure suggests that their altered collagen microarchitecture is more susceptible to enzymatic degradation and may explain the localization of skin lesions in HERDA-affected horses to those areas of the body most exposed to sunlight. These findings appear to support the previously reported benefits of sunlight restriction in HERDA-affected horses.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, 784 Wilson Road G-387, East Lansing, MI, 48824, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Rashmir-Raven
authors.affiliation: Laboratory for Comparative Orthopaedic Research, Michigan State University, 784 Wilson Road G-387, East Lansing, MI, 48824, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lavagnino
authors.affiliation: Laboratory for Comparative Orthopaedic Research, Michigan State University, 784 Wilson Road G-387, East Lansing, MI, 48824, USA.
authors.forename: Aleksa
authors.initials: A
authors.lastname: Sedlak
authors.affiliation: Laboratory for Comparative Orthopaedic Research, Michigan State University, 784 Wilson Road G-387, East Lansing, MI, 48824, USA.
authors.forename: Keri
authors.initials: K
authors.lastname: Gardner
authors.affiliation: Laboratory for Comparative Orthopaedic Research, Michigan State University, 784 Wilson Road G-387, East Lansing, MI, 48824, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Arnoczky
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D017364:Collagenases / Q000378:metabolism*; D004535:Ehlers-Danlos Syndrome / Q000473:pathology / Q000662:veterinary*; D020022:Genetic Predisposition to Disease; D006734:Horse Diseases / Q000473:pathology*; D006736:Horses; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D013718:Tensile Strength
chemical_list: D017364:Collagenases