A Mutation in the SUV39H2 Gene in Labrador Retrievers with Hereditary Nasal Parakeratosis (HNPK) Provides Insights into the Epigenetics of Keratinocyte Differentiation.

Peer reviewe

Intradermal injection of heat-killed Mycobacterium vaccae in dogs with atopic dermatitis: a multicentre pilot study

Canine atopic dermatitis (cAD) is a common disease with a multifactorial aetiology associated with impaired immunoregulation. The immunopathogenesis has similarities to that of human atopic dermatitis. Clinical signs of allergic disease in humans and mice are reduced by administration of saprophytic mycobacteria that amplify regulatory cytokines and hence the effect of Mycobacterium vaccae on the clinical severity of cAD was investigated. Sixty-two dogs with cAD, selected according to strict criteria, were treated with a single intradermal injection and evaluated monthly for 3 months in a placebo-controlled double-blind clinical trial. Clinical severity was quantified using standardized scores and by owner assessment of pruritus. A single injection of a heat-killed suspension of M. vaccae was found to be well tolerated and effective in treating mild to moderate cases of cAD demonstrable for 3 months, but was insignificant in more severely affected dogs

Whole genome scan identifies several chromosomal regions linked to equine sarcoids.

Despite the evidence for a genetic predisposition to develop equine sarcoids (ES), no whole genome scan for ES has been performed to date. The objective of this explorative study was to identify chromosome regions associated with ES. The studied population was comprised of two half-sibling sire families, involving a total of 222 horses. Twenty-six of these horses were affected with ES. All horses had been previously genotyped with 315 microsatellite markers. Quantitative trait locus (QTL) signals were suggested where the F statistic exceeded chromosome-wide significance at P < 0.05. The QTL analyses revealed significant signals reaching P < 0.05 on equine chromosome (ECA) 20, 23 and 25, suggesting a polygenic character for this trait. The candidate regions identified on ECA 20, 23 and 25 include genes regulating virus replication and host immune response. Further investigation of the chromosome regions associated with ES and of genes potentially responsible for the development of ES could form the basis for early identification of susceptible animals, breeding selection or the development of new therapeutic targets

FAM83G/Fam83g genetic variants affect canine and murine hair formation.

FAM83G/Fam83g genetic variants have been described in dogs, mice and recently also in humans. They are associated with palmoplantar keratoderma and altered hair or coat phenotype, reported as wooly phenotype in mice. FAM83G/Fam83g is an unexplored effector of temporally and spatially coordinated Wnt and BMP signalling which are key pathways in pre- and postnatal hair follicle morphogenesis and differentiation. The aim of this study was to unravel phenotypic consequences of FAM83G/Fam83g variants on hair coat formation in dogs and mice. Our results show differences in hair types and hair shaft structures in both species. Additionally, mice exhibit deregulated hair cycle progression which timely correlates with defective Wnt signalling (Axin2) and Bmp2/4 expression. These results affirm the involvement of FAM83G in hair morphogenesis, hair follicle differentiation and cycling

Abnormal keratinocyte differentiation in the nasal planum of Labrador Retrievers with hereditary nasal parakeratosis (HNPK).

Hereditary nasal parakeratosis (HNPK) is an inherited disorder described in Labrador Retrievers and Greyhounds. It has been associated with breed-specific variants in the SUV39H2 gene encoding a histone 3 methyltransferase involved in epigenetic silencing. Formalin-fixed biopsies of the nasal planum of Labrador Retrievers were screened by immunofluorescence microscopy for the presence and distribution of epidermal proliferation and differentiation markers. Gene expression of these markers was further analysed using RNA sequencing (RNA-seq) and ultrastructural epidermal differences were investigated by electron microscopy. Differentiation of the nasal planum in the basal and suprabasal epidermal layers of HNPK-affected dogs (n = 6) was similar compared to control dogs (n = 6). In the upper epidermal layers, clear modifications were noticed. Loricrin protein was absent in HNPK-affected nasal planum sections in contrast to sections of the same location of control dogs. However, loricrin was present in the epidermis of paw pads and abdominal skin from HNPK dogs and healthy control dogs. The patterns of keratins K1, K10 and K14, were not markedly altered in the nasal planum of HNPK-affected dogs while the expression of the terminal differentiation marker involucrin appeared less regular. Based on RNA-seq, LOR and IVL expression levels were significantly decreased, while KRT1, KRT10 and KRT14 levels were up-regulated (log2fold-changes of 2.67, 3.19 and 1.71, respectively) in HNPK-affected nasal planum (n = 3) compared to control dogs (n = 3). Electron microscopical analysis revealed structural alterations in keratinocytes and stratum corneum, and disrupted keratinocyte adhesions and distended intercellular spaces in lesional samples (n = 3) compared to a sample of a healthy control dog (n = 1). Our findings demonstrate aberrant keratinocyte terminal differentiation of the nasal planum of HNPK-affected Labrador Retrievers and provide insights into biological consequences of this inactive SUV39H2 gene variant

Macrococcus canis and M. caseolyticus in dogs: occurrence, genetic diversity and antibiotic resistance

BACKGROUND: The discovery of a new Macrococcus canis species isolated from skin and infection sites of dogs led us to question if Macrococcus spp. are common in dogs and are resistant to antibiotics. HYPOTHESIS/OBJECTIVES: To evaluate the occurrence of Macrococcus spp. in dogs, determine antibiotic resistance profiles and genetic relationships. ANIMALS: One hundred and sixty two dogs (mainly West Highland white terriers and Newfoundland dogs) were screened for the presence of Macrococcus, including six dogs with Macrococcus infections. METHODS: Samples were taken from skin, ear canal and oral mucosa using swabs. Macrococci were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry, 16S rRNA sequencing and nuc-PCR. Minimal inhibitory concentrations of 19 antibiotics were determined using broth microdilution. Resistance mechanisms were identified by microarray and sequencing of the fluoroquinolone-determining region of gyrA and grlA. Sequence type (ST) was determined by multilocus sequence typing. RESULTS: Out of the 162 dogs, six harboured M. caseolyticus (n = 6) and 13 harboured M. canis (n = 16). Six isolates of M. canis and one of M. caseolyticus were obtained from infection sites. The 22 M. canis strains belonged to 20 different STs and the seven M. caseolyticus strains to three STs. Resistance to antibiotics was mostly associated with the detection of known genes, with mecB-mediated meticillin resistance being the most frequent. CONCLUSION AND CLINICAL IMPORTANCE: This study gives some insights into the occurrence and genetic characteristics of antibiotic-resistant Macrococcus from dogs. Presence of M. canis in infection sites and resistance to antibiotics emphasized that more attention should be paid to this novel bacteria species

Additional file 1: of Otitis in a cat associated with Corynebacterium provencense

Annotations of Gap regions comparing 17KM38 and SN15. The genome sequences of 17KM38 and SN15 were compared with mauve and gap regions extracted. Annotations of these regions are shown here (XLSX 21 kb)

Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X

<div><p>Alopecia X is a hair cycle arrest disorder in Pomeranians. Histologically, kenogen and telogen hair follicles predominate, whereas anagen follicles are sparse. The induction of anagen relies on the activation of hair follicle stem cells and their subsequent proliferation and differentiation. Stem cell function depends on finely tuned interactions of signaling molecules and transcription factors, which are not well defined in dogs. We performed transcriptome profiling on skin biopsies to analyze altered molecular pathways in alopecia X. Biopsies from five affected and four non-affected Pomeranians were investigated. Differential gene expression revealed a downregulation of key regulator genes of the Wnt (<i>CTNNB1</i>, <i>LEF1</i>, <i>TCF3</i>, <i>WNT10B</i>) and Shh (<i>SHH</i>, <i>GLI1</i>, <i>SMO</i>, <i>PTCH2</i>) pathways. In mice it has been shown that Wnt and Shh signaling results in stem cell activation and differentiation Thus our findings are in line with the lack of anagen hair follicles in dogs with Alopecia X. We also observed a significant downregulation of the stem cell markers <i>SOX9</i>, <i>LHX2</i>, <i>LGR5</i>, <i>TCF7L1</i> and <i>GLI1</i> whereas <i>NFATc1</i>, a quiescence marker, was upregulated in alopecia X. Moreover, genes coding for enzymes directly involved in the sex hormone metabolism (<i>CYP1A1</i>, <i>CYP1B1</i>, <i>HSD17B14</i>) were differentially regulated in alopecia X. These findings are in agreement with the so far proposed but not yet proven deregulation of the sex hormone metabolism in this disease.</p></div