Correlation of Histopathology and Clinical Presentation

A minority of human patients with non-syndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in ICHTHYIN (NIPAL4). This protein is thought to play a role in epidermal lipid metabolism, although the mechanism is unknown. A mild to moderate form of ICHTHYIN associated ARCI was identified in an extended pedigree of American bulldogs. The gross phenotype was evidenced by a disheveled pelage shortly after birth. All dogs had persistent generalized scaling, as well as adherent brown scale with erythema of the abdominal skin. Pedigree analysis was highly suggestive of an autosomal recessive mode of inheritance. Ultrastructurally, the epidermis showed abnormal lipid processing evidenced by discontinuous lipid bilayers in the stratum corneum, unprocessed lipid within corneocytes, and clear vacuoles within lamellar bodies. Linkage analysis revealed an association with NIPAL4, and an SINE insertion upstream of exon 1 in a highly conserved region was discovered and believed to be the cause of disease. Out of 545 DNA samples from American bulldogs, 32 dogs (17 females, 15 males,) were homozygous for the larger PCR fragment. All affected dogs were homozygous, with parents heterozygous for the insertion. Expression of NIPAL4, assessed by immunolabeling, showed an absence of ichthyin in the granular cell layer of the epidermis. This is the first description of a spontaneous autosomal recessive congenital ichthyosis associated with decreased expression of NIPAL4 in a nonhuman species. Funding: The Commonwealth of Pennsylvania, International Society for Veterinary Dermatopathology, National Institutes of Health – OD010939 Canine Epidermal Neural Crest Stem Cells – Characterization, Isolation and Expansion Barbara Gericota1, Joseph S. Anderson1, Gaela Mitchell1, Dori L. Borjesson2, Beverly K. Sturges2, Jan A. Nolta1, Maya Sieber-Blum3 (1) Stem Cell Program, Institute for Regenerative Cures, University of California Davis, USA (2) School of Veterinary Medicine, University of California, Davis, USA (3) Institute of Genetic Medicine, Newcastle University, UK The embryonic neural crest has the ability to generate an astonishing variety of cell types and tissues in the adult vertebrate organism. The discovery of neural crest stem cells in an adult, readily accessible location opens a variety of opportunities for patient-specific therapies. We present, characterize, and provide protocols for the isolation of canine epidermal neural crest stem cells (cEPI-NCSC) remnants of the embryonic neural crest in the adult hair follicle. Furthermore, we developed novel tools for research in canines. Similar to human and mouse EPINCSC, the neural crest origin of cEPI-NCSC is shown at the RNA and protein levels by expression of neural crest molecular signature and other neural crest-characteristic genes. In parallel to human EPI-NCSC, cEPI-NCSC also expressed pluripotency genes. We showed that cEPI-NCSC could generate call major neural crest derivatives. Multipotency and ability to selfrenewal were demonstrated by in vitro clonal analyses, establishing cEPI-NCSCs as multipotent somatic cells. A critical literature analysis on canine spinal cord injury (SCI) showed the need for novel treatments and suggested that cEPI-NCSC represent viable candidates for cell-based therapies in dogs with SCI. This concept is supported by the close ontological relationship between neural crest stem cells and spinal cord stem cells. Together, we provide the groundwork for the development of a novel cell-based therapy for a condition with poor prognosis and limited treatment options. Funding This project was supported by Medical Research Council Grant 22358, UK (M.S.-B.), the Center for Equine Health, UC-Davis (B.G.), a gift from Dick and Carolyn Randall (J.N., D.B., B.G.), and by Fundacao para a Ciencia e a Tecnologia, Ministerio da Educacao e Ciencia, Portugal, under the Individual Doctoral Grant SFRH/ BD/ 64871/2009 (B.G.). Conflict of Interest The authors indicate no potential conflicts of interest. THE MILLIONS OF MICROORGANISMS INHABITING THE SKIN: THE CANINE SKIN MICROBIOME Rodrigues Hoffmann A1, Patterson AP2, Diesel A2, Lawhon SD3, Ly HJ1, Stephenson C4, Mansell J1, Steiner JM4, Dowd SE5, Olivry T6, Suchodolski JS4 1Dermatopathology Specialty Service, Department of Veterinary Pathobiology; 2Clinical Dermatology Service, Department of Small Animal Clinical Sciences; 3Clinical Microbiology Laboratory, Department of Veterinary Pathobiology, 4Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 5MR DNA Laboratory, Shallowater, Texas 6Department of Clinical Sciences, College of Veterinary Medicine, and Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC [email protected] INTRODUCTION Molecular-based sequencing studies targeting the bacterial 16S rRNA gene have revealed that the skin surface of humans is inhabited by a diverse and variable microbial population composed of commensal, symbiotic, and pathogenic bacteria, defined as the microbiome. Recent studies have shown that an imbalance in these microbial populations may result in damage to the skin, and development of skin lesions, although it is still unknown if an altered microbiome is the cause of skin lesions, or the result of an altered skin barrier. The skin microbiome can be altered by host factors including presence of hair follicles, temperature, pH, moisture, environmental contact, and contact with mucous membranes. These different factors will influence the different skin microenvironments, which can be divided into dry, moist and sebaceous regions.