An inherited connective tissue disease in the horse.

This research study examines a potentially inherited connective tissue disease in two related horses, characterized by hyperextendable, fragile skin. The disease is compared to a similar disease in humans, known as Ehlers-Danlos Syndrome and to dominant collagen packing defects in other animals. The study suggests that the disease might be inherited through an autosomal dominant or recessive mutation.

Methodology and Detailed Observations

• The researchers compared the skin of the two affected horses with the skin of eight normal horses. This involved examination of the skin sections using light microscopy and transmission electron microscopy.
• It was observed that the deep dermal layer of the dorsal abdomen in affected horses was significantly thinner. This layer contained collagen fibers that were loosely packed, as compared to normal horses.
• Within individual fibers in the affected horses, the fibrils (smaller units comprising a fiber) were often curved and non-parallel, contrasting with the straight and parallel arrangement found in normal horses.
• The affected horses exhibited a wider range of fibril diameters, including some unusually thick fibrils with irregular outlines. Such features were not observed in the normal horses.

Chemical Analysis and Comparison

• An acetic acid extraction of other skin samples was carried out, followed by pepsin digestion, amino acid analysis, and polyacrylamide gel electrophoresis.
• The results showed that in the two affected horses, the proportion of total extracted collagen that was soluble in acid was twice as high as that in two normal horses.
• Collagen types I and III were found in similar proportions in both normal and affected horses, and the molecular weights of the collagen chains were also normal.

Inference and Associations

• The researchers concluded that the disorder in these horses resembles the group of conditions described by Minor (Minor RR: Am J Pathol 98: 226, 1980) as ‘dominant collagen packing defect I’. This group of conditions has been reported in dogs, mink, and cats, and share features with Ehlers-Danlos Sydrome I, II, and III in humans, which is a group of disorders affecting connective tissues.
• The pedigree data of the horses suggested that the traits could be due to an autosomal recessive mutation, where an individual must inherit two copies of the mutant gene for the trait to manifest. However, the data was also consistent with autosomal dominant inheritance, where inheritance of only one copy of the mutant gene leads to manifestation of the trait.