Abstract
Similar to humans, the horse relies predominantly on the evaporation of sweat from the skin surface to dissipate excess body heat. Loss of the sweat response or anhidrosis can result in life-threatening hyperthermia. Anhidrosis occurs more frequently in some breeds as well as occurs at an increased frequency among individuals with a family history, suggesting a heritable component to the pathology. Given the natural occurrence and indications of genetic components in the etiology, we utilized genomics to better understand the molecular mechanisms involved in sweat response. We performed a case-control (n= 200) GWAS targeting cases of chronic idiopathic anhidrosis in a controlled genetic background to discover the contributing regions and interrogated gene function for roles in the sweating mechanism. A region containing the KCNE4 gene, which encodes the β-subunit of a potassium channel protein with a possible function in sweat gland outflow, was associated (P= 1.13× 10-07) with chronic idiopathic anhidrosis through GWAS. A candidate mutation (NC_009149.3:g.11813731A > G, rs68643109) disrupting the KCNE4 protein structure could explain the disease but requires further investigation in larger populations. We show the potential role of ion channels and cellular damage in sweat response, correlating anhidrosis as a possible effect of congenital channelopathy.
Highlights
Anhidrosis is the loss of the ability to sweat in response to appropriate stimuli (Breuhaus, 2009)
Insights from the survey Previous work examining the epidemiology of anhidrosis successfully relied solely on owner- and veterinarianreported diagnoses; we applied a similar approach (Johnson et al, 2010; Mayhew and Ferguson, 1987; Warner and Mayhew, 1982)
Regional advertising strategies resulted in over-representation of responses for horses in Florida and Louisiana, we received reports of chronic idiopathic anhidrosis (CIA)
Summary
Anhidrosis is the loss of the ability to sweat in response to appropriate stimuli (Breuhaus, 2009). Equine sweat production begins with the secretion of a mixture of water, proteins, and electrolytes into a coiled tubular fundus within the gland (Evans et al, 1956a; Kerr and Snow, 1983). Within the equine sweat gland, serpentine excretory ducts associate closely with hair follicles, a characteristic of apocrine-type glands despite the eccrine-type function (Evans et al, 1956a; Jenkinson et al, 2007). Thermoregulation in the horse utilizes hair erection and a large transpiration capacity through the sweat glands distributed across nearly the entire
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