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The aim of this study was to characterize the phenotype and to identify the genetic etiology of a syndromic form of ichthyosis congenita (IC) observed in Italian Chianina cattle and to estimate the prevalence of the deleterious allele in the population. Sporadic occurrence of different forms of ichthyosis including IC have been previously reported in cattle. However, so far, no causative genetic variant has been found for bovine IC. Nine affected cattle presenting congenital xerosis, hyperkeratosis and scaling of the skin as well as urolithiasis and cystitis associated with retarded growth were examined. Skin histopathology revealed a severe, diffuse orthokeratotic hyperkeratosis with mild to moderate epidermal hyperplasia. The pedigree records indicated a monogenic recessive trait. Homozygosity mapping and whole-genome sequencing allowed the identification of a homozygous frameshift 1 bp insertion in the FA2H gene (c.9dupC; p.Ala4ArgfsTer142) located in a 1.92 Mb shared identical-by-descent region on chromosome 18 present in all cases, while the parents were heterozygous as expected for obligate carriers. These findings enable the selection against this sub-lethal allele showing an estimated frequency of ~ 7.5% in Chianina top sires. A sporadic incidence of mild clinical signs in the skin of heterozygous carriers was observed. So far, pathogenic variants affecting the encoded fatty acid 2-hydroxylase catalyzing the synthesis of 2-hydroxysphingolipids have been associated with myelin disorders. In conclusion, this study represents the first report of an FA2H-related autosomal recessive inherited skin disorder in a mammalian species and adds FA2H to the list of candidate genes for ichthyosis in humans and animals. Furthermore, this study provides a DNA-based diagnostic test that enables selection against the identified pathogenic variant in the Chianina cattle population. However, functional studies are needed to better understand the expression of FA2H in IC-affected Chianina cattle.

Canine cutaneous mast cell tumors (ccMCTs) are currently graded according to Patnaik and Kiupel grading schemes. The qualitative and semiquantitative parameters applied in these schemes may lead to inter- and intraobserver variability. This study investigates the prognostic value of volume-weighted mean nuclear volume ([Formula: see text]), a stereological estimation that provides information about nuclear size and its variability. [Formula: see text] of 55 ccMCTs was estimated using the “point-sampled intercept” method and compared with histological grade and clinical outcome. The clinical history of dogs treated with surgical excision alone was available for 30 ccMCTs. Statistical differences in [Formula: see text] were found between grade II ([Formula: see text]= 115 ± 29 µm3) and grade III ccMCTs ([Formula: see text]= 197 ± 63 µm3), as well as between low-grade ([Formula: see text]= 113 ± 28 µm3) and high-grade ccMCTs ([Formula: see text]= 184 ± 63 µm3). An optimal cutoff value of [Formula: see text] ≥ 150 µm3 and [Formula: see text] ≥ 140 µm3 was determined for grade III and high-grade ccMCTs, respectively. In terms of prognosis, [Formula: see text] was not able to predict the clinical outcome in 42% of the cases; however, cases with [Formula: see text]3 had a favorable outcome. These results indicate that, despite having limited prognostic value when used as a solitary parameter, [Formula: see text] is highly reproducible and is associated with histological grade as well as with benign behavior.

A tool to study SARS-CoV-2 Work with infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires high-level biocontainment facilities, making it important to develop safer molecular tools that can potentially be used under less stringent conditions. Self-replicating RNAs known as replicons have long been used to study pathogenic RNA viruses; however, developing replicons to study SARS-SoV-2 has been challenging because of its large genome. Ricardo-Lax et al . used a yeast-based system to construct SARS-CoV-2 replicons that cannot assemble infectious virus because they lack the spike protein required for host cell entry. Transfecting cells with a spike-expressing plasmid and separately with the replicon generates replicon delivery particles (RDPs) that are only capable of one cycle of infection. The replicons and the RDPs can be used in different contexts for drug screening, and viral assays. —VV

We report necropsy findings in a captive 60-year-old female greater flamingo (Phoenicopterus roseus) that died suddenly following rupture of a pulmonary artery aneurysm. Histologically, there was focally extensive, intramural granulomatous inflammation with intralesional fungal hyphae, and adjacent severe mixed-cell inflammation and acute haemorrhage at the rupture site. Aspergillus fumigatus was identified as the aetiological agent following DNA PCR amplification and sequencing from paraffin-embedded pulmonary artery tissue sections. The most likely explanation is that this lesion was a consequence of haematogenous spread, secondary to mycotic pneumonia or aerosacculitis, following aspiration of A. fumigatus conidiospores. However, no further fungal-related lesions were observed on gross or histopathological examination.

The avian pathogen Ornithobacterium rhinotracheale (ORT) has been implied in the etiology of poultry respiratory disease in recent years. To evaluate whether Whatman® Flinders Technology Associates (FTA®) cards can be used for hazard-free transport and storage of ORT samples for posterior DNA amplification, a controlled assay was performed. Three 10-fold dilutions of an ORT culture suspension were spotted on FTA cards and stored at room temperature (RT) for 6 mo. Sterile swabs were immersed in the same three 10-fold culture dilutions and stored at RT and 4 and -20 C without storage medium for the same time. DNA was extracted from both the FTA cards and swabs 1 day, 1 and 6 wk, and 6 mo following sample preparation and stored at -20 C. At the end of the experiment, real-time PCR amplification of the 16S ribosomal RNA gene was performed from DNA extracted throughout a 6-mo period from all ORT samples stored on both FTA cards and swabs. The obtained threshold cycle values for each ORT DNA extraction date were within the same range for all samples in a dilution-dependent fashion, regardless of storage temperature or used material. Pure ORT colonies could be reisolated 1 day after sample preparation from the swab dilutions stored at all temperatures but not from the FTA cards. We conclude that the efficiency of ORT DNA amplification from samples stored on FTA cards or in swabs is similar. However, FTA cards have the advantage of preventing microorganism growth, thus allowing safe transport and storage, for at least 6 mo, for bacterial dilutions down to at least 104-105 colony-forming units/ml.

Several cauliflower-like alopecic masses arose on the head of an otherwise healthy, full-term newborn Jersey × Belgian blue heifer, which was humanely destroyed shortly after birth due to the severity of the skin lesions. Microscopically, the masses were composed of multiple papillary projections displaying well-differentiated sebaceous glands surrounded by a moderate number of well-developed sweat glands, as well as embryonic and fully developed, but dysplastic hair follicles. Thick branching connective tissue stalks supported these adnexal components. The papillated surface, the predominance of sebaceous glands, the presence of embryonic hair follicles and the well-differentiated sweat glands were compatible with nevus sebaceous, a rare form of cutaneous hamartoma described in man, dogs, cats and cattle. However, the cauliflower-like growth pattern, the presence of supportive thick branching connective tissue stalks and the relative abundance of dysplastic hair follicles in association with nevus sebaceous has not been described in the human or veterinary literature. A diagnosis of panadnexal papillomatous hamartoma was made in this case.

A 6‐day‐old Belgian Blue‐Holstein calf was referred because of a syndrome resembling epidermolysis bullosa simplex (EBS). The clinical phenotype included irregular and differently sized erosions and ulcerations spread over the body, in particular on the limbs and over bone prominences, as well as in the nasal planum and oral mucosa. Blisters were easily induced by rubbing the skin. The skin lesions displayed a clear dermal‐epidermal separation at the level of the basal cell layer. Post mortem examination revealed erosions in the pharynx, proximal esophagus, and rumen. Whole‐genome sequencing revealed a heterozygous disruptive in‐frame deletion variant in KRT5 (c.534_536delCAA). Genotyping of both parents confirmed the variant as de novo mutation. Clinicopathological and genetic findings were consistent with the diagnosis of KRT5‐related EBS providing the second example of a spontaneous mutation causing epidermolysis bullosa in cattle.

Genetic skin diseases in cattle are rare.A 7-week-old female Holstein calf was presented with epidermal lesions and alopecia in the caudal region of the ears and on the neck, as well as deep bilateral ulcerative lesions on the palmar aspect of the metacarpi and dorsal aspect of the right metacarpus. Clinical, pathological and histopathological examination of the calf was suggestive of a subepidermal vesicular dermatosis. Genetic analysis identified a de novo non-sense variant affecting the aspartate dehydrogenase domain containing (ASPDH) gene, which might be associated with the formation of subepidermal vesicles in this case.The observed phenotype in the calf may represent a novel form of a vesicular skin disorder. Haploinsufficiency of the ASPDH gene might be considered as a possible cause.Les dermatoses génétiques bovines sont rares. RÉSUMÉ CLINIQUE: Une Holstein femelle de 7 semaines a été présentée avec des lésions épidermiques et une alopécie en région caudale des pavillons et sur le cou, ainsi que des lésions ulcératives profondes bilatérales sur la face palmaire des métacarpes et ma face dorsale du métacarpe droit. L’examen clinique, pathologique et histopathologique du veau était évocateur de dermatose vésiculeuse sous épidermique. L'analyse génétique a identifié un variant non sens de novo atteignant le gène contenant le domaine ASPDH (aspartate dehydrogenase) qui pourrait être associé avec la formation de vésicules sous-épidermiques dans ce cas.Le phénotype observé chez le veau pourrait représenter une nouvelle forme d'un trouble cutané vésiculeux. L'haplo-insuffisance du gène ASPDH pourrait en être considéré comme une cause possible.INTRODUCCIÓN: las enfermedades genéticas de la piel en el ganado vacuno son poco frecuentes. RESUMEN CLÍNICO: se presentó a una ternera Holstein hembra de 7 semanas de edad con lesiones epidérmicas y alopecia en la región caudal de las orejas y el cuello, así como lesiones ulcerativas bilaterales profundas en el aspecto palmar de los metacarpianos y el aspecto dorsal del metacarpo derecho. El examen clínico, patológico e histopatológico de la ternera sugirió una dermatosis vesicular subepidérmica. El análisis genético identificó una nueva mutación sin sentido (proteína truncada) que afecta al gen que contiene el dominio de la aspartato deshidrogenasa (ASPDH), y que podría estar asociado con la formación de vesículas subepidérmicas en este caso. CONCLUSIÓN E IMPORTANCIA CLÍNICA: el fenotipo observado en la ternera puede representar una nueva variante de enfermedad vesicular de la piel. La haploinsuficiencia del gen ASPDH podría considerarse como una posible causa.Genetische Hauterkrankungen bei Rindern sind selten.Ein 7 Wochen altes Holsteinkalb wurde mit epidermalen Veränderungen und einer Alopezie in der Region caudal der Ohren und am Nacken, sowie tiefen bilateralen ulzerativen Läsionen an der palmaren Seite der Metacarpi und dorsal am rechten Metacarpus vorgestellt. Eine klinische, pathologische und histopathologische Untersuchung des Kalbes wies auf eine subepidermale vesikuläre Dermatose hin. Die genetische Analyse identifizierte eine de novo non-sense Variante, die die Domäne des Gens der Aspartatdehydrogenase betraf, welche mit der Bildung von subepidermalen Bläschen in diesem Fall im Zusammenhang stehen dürften.Der beobachtete Phänotyp bei diesem Kalb könnte eine neue Form von vesikulärer Hauterkrankung darstellen. Eine Haploinsuffizienz des ASPDH Gens könnte als mögliche Ursache betrachtet werden.背景: 牛の遺伝性皮膚疾患はまれである。 臨床概要: 7週齢のホルスタイン種の子牛に、表皮病変および耳介尾側および頸部の脱毛症、ならびに中手骨の手掌側面および右中手骨の背面側面の深部両側潰瘍性病変が認められた。 子牛の臨床的、病理学的および組織病理学的検査は、表皮下水疱性皮膚症を示唆していた。 遺伝子解析により、アスパラギン酸デヒドロゲナーゼドメインを含む（ASPDH）遺伝子に影響を及ぼすde novoナンセンス変異体を同定し、本症例においては、この変異が表皮下水疱の形成に関連している可能性がある。 結論と臨床的重要性: 子牛で観察された表現型は、水疱性皮膚障害の新しい形態を表している可能性がある。 ASPDH遺伝子のハプロ不全は、発症要因の一つの可能性として考えられるかもしれない。.背景: 牛的遗传性皮肤病很罕见。 临床总结: 7周龄雌性荷斯坦犊牛，耳背侧和颈部有表皮病变和脱毛，掌骨掌侧和右侧掌骨背侧有双侧深层溃疡性病变。临床、病理和组织病理学检查提示小腿表皮下水疱性皮肤病。遗传分析发现的影响天门冬氨酸脱氢酶域(ASPDH)基因全然无意义的变异，可能与本病例中皮下水泡的形成有关。 结论和临床意义: 本文的小腿发病表型可能代表了一种新型水泡性皮肤病。原因可能是ASPDH基因的单倍体不足。.As doenças genéticas da pele em bovinos são raras. DADOS CLÍNICOS: Uma bezerra da raça holandesa de sete semanas de idade foi apresentada com lesões epidérmicas e alopecia na região caudal das orelhas e no pescoço, além de lesões ulcerativas profundas bilaterais no aspecto palmar dos metacarpos e no aspecto dorsal do metacarpo direito. O exame clínico, patológico e histopatológico da bezerra foi sugestivo de dermatose vesicular subepidérmica. A análise genética identificou uma variante que afeta o gene do domínio da aspartato desidrogenase (ASPDH), que pode estar associado à formação das vesículas subepidérmicas nesse caso. CONCLUSÃO E IMPORTÂNCIA CLÍNICA: O fenótipo observado na bezerra pode representar uma nova forma de distúrbio vesicular cutâneo. A haploinsuficiência do gene ASPDH pode ser uma causa provável.

International audience; Marek's disease virus (MDV) is an alphaherpesvirus that causes lethal T-cell lymphomas in chickens. MDV is unique in that it harbors two copies of a viral telomerase RNA subunit (vTR) in its genome exhibiting 88% sequence identity to the chicken orthologue, chTR. The minimal telomerase ribonucleoprotein complex consists of a protein subunit with reverse transcriptase activity (TERT) and TR. Physiologically, the complex compensates for the progressive telomere shortening that occurs during mitosis and is involved in the process of cellular immortalization. Previous studies showed that MDV vTR performes an auxiliary function during oncogenesis. Comparative in vitro analysis of the viral and chicken TR promoters revealed that the vTR promoter (PvTR) was up to 3-fold more efficient than the chTR promoter (PchTR) in avian cells and that the stronger transcriptional activity of PvTR resulted largely from an E-box located two nucleotides downstream of the transcriptional start site of the vTR gene. To test the hypothesis that PvTR is required for vTR expression and, hence, efficient tumor formation, we generated a recombinant virus, vPchTR+/+, in which the vTR promoter was replaced by that of chTR. In vivo, growth of vPchTR+/+ was indistinguishable from that of parental virus; however, tumor induction was reduced by > 50% and lymphomas were smaller and less disseminated when compared to those induced by parental virus. We concluded that PvTR is not required for lytic replication in vivo but is essential for efficient transcription of vTR and thereby critical for efficient MDV lymphoma formation.

Marek’s disease virus (MDV) encodes an ubiquitin-specific protease (USP) within its UL36 gene. USP is highly conserved among herpesviruses and was shown to be important for MDV replication and pathogenesis in MDV’s natural host, the chicken. To further investigate the role of MDV USP, several recombinant (r) MDVs were generated and their in vitro phenotypes were evaluated using plaque size and growth kinetics assays. We discovered that the N-terminus of pUL36 is essential for MDV replication and could not be complemented by ectopic expression of MDV USP. In addition, we demonstrated that the region located between the conserved glutamine (Q85) and leucine (L106) residues comprising the active site cysteine (C98) is also essential for MDV replication. Based on the analyses of the rMDVs generated here, we concluded that MDV USP likely contributes to the structure and/or stability of pUL36 and affects replication and oncogenesis of MDV beyond its enzymatic activity.

Genodermatoses, such as heritable skin disorders, mostly represent Mendelian conditions. Congenital hypotrichosis (HY) characterize a condition of being born with less hair than normal. The purpose of this study was to characterize the clinicopathological phenotype of a breed-specific non-syndromic form of HY in Hereford cattle and to identify the causative genetic variant for this recessive disorder. Affected calves showed a very short, fine, wooly, kinky and curly coat over all parts of the body, with a major expression in the ears, the inner part of the limbs, and in the thoracic-abdominal region. Histopathology showed a severely altered morphology of the inner root sheath (IRS) of the hair follicle with abnormal Huxley and Henle’s layers and severely dysplastic hair shafts. A genome-wide association study revealed an association signal on chromosome 5. Homozygosity mapping in a subset of cases refined the HY locus to a 690 kb critical interval encompassing a cluster of type II keratin encoding genes. Protein-coding exons of six positional candidate genes with known hair or hair follicle function were re-sequenced. This revealed a protein-changing variant in the KRT71 gene that encodes a type II keratin specifically expressed in the IRS of the hair follicle (c.281delTGTGCCCA, p.Met94AsnfsX14). Besides obvious phenocopies, a perfect concordance between the presence of this most likely pathogenic loss-of-function variant located in the head domain of KRT71 and the HY phenotype was found. This recessive KRT71-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002114-9913).