A nonsense variant in the KRT14 gene in a domestic shorthair cat with epidermolysis bullosa simplex.

Epidermolysis bullosa simplex (EBS) is a hereditary blistering disease affecting the skin and mucous membranes. It has been reported in humans, cattle, buffaloes and dogs, but so far not in cats. In humans, EBS is most frequently caused by variants in the KRT5 or KRT14 genes. Here, we report a case of feline epidermolysis bullosa simplex and describe the causative genetic variant. An 11-month-old male domestic shorthair cat presented with a history of sloughed paw pads and ulcerations in the oral cavity and inner aspect of the pinnae, starting a few weeks after birth. Clinical and histopathological findings suggested a congenital blistering disease with a split formation within the basal cell layer of the epidermis and oral mucous epithelium. The genetic investigation revealed a homozygous nonsense variant in the KRT14 gene (c.979C>T, p.Gln327*). Immunohistochemistry showed a complete absence of keratin 14 staining in all epithelia present in the biopsy. To the best of our knowledge, this is the first report of feline EBS, and the first report of a spontaneous pathogenic KRT14 variant in a non-human species. The homozygous genotype in the affected cat suggests an autosomal recessive mode of inheritance.

A Fibromyxoid Stromal Response is Associated with Muscle Invasion in Canine Urothelial Carcinoma.

Canine urothelial carcinoma (UC) is the most common type of cancer of the lower urinary tract and tends to affect elderly neutered female dogs, with a high predisposition for Scottish terriers. Tumour stroma, inflammation and necrosis are poorly characterized in canine UC and their role as prognostic factors is unknown. The aims of this study were to (1) assess histologically 381 canine UCs, with emphasis on myxoid tumour stroma, inflammation and necrosis and (2) assess possible associations between these features and the available epidemiological data as well as bladder wall muscle invasion. In 103 of 381 (27%) cases, the stroma was mixed collagenous and myxoid (fibromyxoid), which was strongly associated with invasive growth of muscle (P <0.0001). Peritumoural and intratumoural inflammation was present in 308 of 345 (89%) and 287 of 381 (75%) cases, respectively, and was mostly mild and lymphoplasmacytic. One hundred and fifteen of the 381 (30%) cases showed a variable eosinophilic inflammation and 58 of 381 (15%) presented with formations of one or several lymphoid follicles. Twenty-four percent (91 of 381) of cases had tumour necrosis, which was typically mild. In 83 of 91 (91%) cases, the necrosis was comedo-like. Moderate to severe tumour necrosis was associated with the presence of moderate to predominant fibromyxoid tumour stroma (P <0.02). The results of this study indicate that fibromyxoid stroma is common in canine UC and is a strong indicator for invasive growth of muscle, which is consistent with a poor prognosis. Based on histomorphology, tumour necrosis in canine UC is best described as comedonecrosis.

A frameshift variant in the EDA gene in Dachshunds with X-linked hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a genetic disease characterized by hypoplasia or absence of hair, teeth and sweat glands. The EDA gene, located on the X chromosome, encodes the type II transmembrane protein ectodysplasin A. Variants in the EDA gene can lead to XLHED in humans, mice, cattle and dogs. In the present study, we investigated a litter of Dachshund puppies, of which four male puppies showed clinical signs of XLHED. We performed a candidate gene analysis in one affected puppy and several non-affected relatives. This analysis revealed a single base-pair deletion in the coding sequence of the EDA gene in the affected puppy (NM_001014770.2:c.842delT). The deletion is predicted to cause a frameshift, NP_001014770.1:p.(Leu281HisfsTer22), leading to a premature stop codon which truncates more than one quarter of the EDA protein. Sanger sequencing results confirmed that this variant was inherited from the dam. Based on knowledge about the functional impact of EDA variants in dogs and other species, c.842delT is a convincing candidate causative variant for the observed XLHED in the male puppies.

Bacillus anthracis as a cause of bovine abortion - a necropsy case requiring special biosafety measures.

INTRODUCTION: In spring 2017, the first case of bovine anthrax in 20 years in Switzerland occurred in the canton of Jura. Carcasses of anthrax-deceased animals should not be opened due to the formation of highly resistant spores bearing the risk of environmental contamination and aerosolization. Nevertheless, in the course of this local outbreak, one sick cow from the affected farm, whose blood repeatedly tested negative for Bacillus anthracis, was necropsied after euthanasia under special biosafety precautions at the Institute of Animal Pathology, Vetsuisse-Faculty Bern. Necropsy revealed ventral edema, fetal death, necro-hemorrhagic placentitis and necrotizing iliac lymphadenitis. Bacillus anthracis was isolated only from placenta and altered lymph node. The biosafety measures taken during and after necropsy prevented a contamination of the necropsy environment, which was proven with bacteriological swabs. This case shows that anthrax may elicit unspecific symptoms mimicking other diseases, and veterinarians must be aware of these non-septicemic cases.

[Fanconi-Bickel-Syndrom: a novel genetic disease in Original Braunvieh]. / Fanconi-Bickel-Syndrom: eine bislang unerkannte Erbkrankheit beim Braunvieh.

INTRODUCTION: This case report describes a new genetic disease of the Braunvieh breed in Switzerland. The bovine disorder also occurs in German Fleckvieh, and corresponds to human Fanconi-Bickel syndrome which is an inherited glycogen storage disease caused by mutations of the SLC2A2 gene encoding the glucose transporter GLUT2. This case report describes a single affected Original Braunvieh calf genotyped as homozygous for the FH2-associated SLC2A2 frame shift mutation. The clinical examination showed stunted growth, polyuria and polydipsia, as well as poor claw horn and coat quality. Necropsy revealed a pale cortex of the kidneys and a unilateral renal hypoplasia. Histology showed tubulonephrosis of the proximal tubules with protein- and glucose-rich contents. Glycogen accumulation was not evident in any organ. This finding is different from the reported lesions in two previously described GLUT2-deficient Fleckvieh heifers. In the presented case, growth retardation mainly seems to be associated with renal dysfunction. A direct gene test is available to eliminate the mutant allele from the population.

Sequence and partial functional analysis of canine Bcl-2 family proteins.

Dogs present with spontaneous neoplasms biologically similar to human cancers. Apoptotic pathways are deregulated during cancer genesis and progression and are important for therapy. We have assessed the degree of conservation of a set of canine Bcl-2 family members with the human and murine orthologs. To this end, seven complete canine open reading frames were cloned in this family, four of which are novel for the dog, their sequences were analyzed, and their functional interactions were studied in yeasts. We found a high degree of overall and domain sequence homology between canine and human proteins. It was slightly higher than between murine and human proteins. Functional interactions between canine pro-apoptotic Bax and Bak and anti-apoptotic Bcl-xL, Bcl-w, and Mcl-1 were recapitulated in yeasts. Our data provide support for the notion that systems based on canine-derived proteins might faithfully reproduce Bcl-2 family member interactions known from other species and establish the yeast as a useful tool for functional studies with canine proteins.

[Pneumothorax during right-sided nephrectomy in a heifer]. / Pneumothorax als Komplikation einer rechtsseitigen Nephrektomie bei einem Jungrind.

A 250-kg heifer had signs of colic attributable to urolithiasis of the right kidney. Medical treatment did not result in resolution of clinical signs, and nephrectomy was carried out. The surgery was started with the heifer standing, and the 13th rib was resected. However, during blunt dissection of the kidney, air suddenly entered the pleural space and the heifer had acute severe dyspnoea. The hole in the pleural cavity was sutured and a chest drain was placed. Inhalation anaesthesia was then induced and nephrectomy could be completed without further complications. The heifer was discharged 11 days postoperatively, and was healthy and had been integrated into the herd 12 months after surgery. Pneumothorax must be considered a possible complication of rib resection in right-sided nephrectomy in cattle.

[Pyometra and persistent hymen in an alpaca]. / Pyometra mit persistierendem Hymen bei einem Alpaka.

A 3-year-old female alpaca was referred to the hospital because of tenesmus. Clinical examination revealed a habitual vaginal prolapse with tenesmus during urination and defecation. On vaginoscopic examination a persistent hymen was detected. Ultrasonography of the caudal abdomen showed an echogenic fluid-filled uterus. A diagnostic laparotomy led to diagnosis of pyometra. Following ovariohysterectomy, the recovery was uneventful. One and a half years later the alpaca was again admitted to the hospital because of colic. Based on the findings, a tentative prognosis was provided and the alpaca was euthanized at the request of the owner. At necropsy, a haemorrhagic infarction of a jejunal loop was found due to incarceration in a fibrous adhesion between the vaginal stump and small intestine.

Immunohistochemical expression study of proapoptotic BH3-only protein bad in canine nonneoplastic tissues and canine lymphomas.

The BH3-only protein Bad is a proapoptotic Bcl-2 family member that acts as a sensitizer in intrinsic apoptosis by inactivating antiapoptotic members through heterodimer formation. Bad has been shown to contribute to tumorigenesis, including lymphoma formation in humans and mice, through alteration in expression or functional status. Here, its immunohistochemical expression was analyzed in canine nonneoplastic and lymphoma tissues using tissue microarrays. Bad was expressed in the cytoplasm of a wide range of nonneoplastic tissues, especially epithelial cells. Nonneoplastic lymph nodes displayed weak immunostaining in the follicular germinal centers only. Immunoblotting supported these observations but also revealed presence of nonspecific labeling in some organs. Of 81 lymphomas, 29 (35.8%) displayed moderate to strong immunohistochemical Bad labeling, and a significant expression increase was found in lymphomas (especially B cell and double negative) compared to nonneoplastic lymph nodes. These findings warrant further investigations of the functional status, the involvement of partner proteins, and a possible impact of Bad on prognosis in canine lymphoma.