Bald thigh syndrome in sighthounds

Bald thigh syndrome is a common hair loss disorder in sighthounds. The overall goal of our study was to identify the cause of bald thigh syndrome and the pathological changes associated with it. We approached this aim by comparing skin biopsies and hair shafts of affected and control dogs microscopically as well as by applying high-throughput technologies such as genomics, transcriptomics and proteomics. While the histology is rather unspecific in most cases, trichogram analysis and scanning electron microscopy revealed severe structural abnormalities in hair shafts of affected dogs. This finding is supported by the results of the transcriptomic and proteomic profiling of skin biopsies and hair shafts, respectively, where genes and proteins important for differentiation of the inner root sheath and the assembly of a proper hair shaft were downregulated. Transcriptome profiling of skin biopsies revealed a downregulation of genes encoding 23 hair shaft keratins and 51 keratin associated proteins, as well as desmosomal cadherins and several actors of the BMP signaling pathway, which is important for hair shaft differentiation. To identify differentially expressed proteins in structural abnormal hair shafts, we performed nLC-MS/MS- based proteomic analysis of fractured hair shafts of four dogs with bald thigh syndrome (Greyhounds, n=3, Whippet, n=1) and intact telogen hair shafts of four control dogs (Greyhounds, n=3, Whippet= n=1) plucked on the thighs. Decreased expression of keratin 71 and desmocollin 2 on the mRNA level in skin biopsies corresponded with a reduced protein expression in the hair shafts of affected dogs.