First Report on Medical Treatment and Outcome of Burnt Cattle

The management of livestock affected by fire often comes down to two options: euthanasia or slaughtering. However, the therapeutic approach can be attempted for high-value cattle. The aim of a primary assessment is to identify signs of smoke inhalation injuries, cardiovascular impairment and shock and to determine the severity and extent of burn injuries. Full-thickness burns covering 40% or more of the body are highly unfavorable prognostic factors and are usually fatal. Moreover, it can take several days for the burns to appear in their full extent, leaving the prognosis uncertain. In this case report, the clinical findings, treatment and outcome of two burnt Holstein heifers are described. Daily wound care required cleaning, the removal of eschars and the application of topical antibacterial agents for seven months in order to discharge one heifer. The topical use of honey with a solution of povidone–iodine proved to be affordable and successful, with no residue risks. The other heifer was more severely wounded, and despite the administration of fluid therapy, pain management, anti-oxidants and anti-microbials, after initial stabilization, the animal’s condition worsened, leading to euthanasia. This confirms that the treatment of burnt cattle is possible but challenging due to the late onset of multi-organ failure

A Heterozygous Missense Variant in MAP2K2 in a Stillborn Romagnola Calf with Skeletal-Cardio-Enteric Dysplasia

RASopathies are a group of developmental disorders caused by dominant mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) cell signaling pathway. The goal of this study was to characterize the pathological phenotype of a Romagnola stillborn calf with skeletal-cardio-enteric dysplasia and to identify a genetic cause by whole-genome sequencing (WGS). The calf showed reduced fetal growth, a short-spine, a long and narrow face, cardiac defects and heterotopy of the spiral colon. Genetic analysis revealed a private heterozygous missense variant in MAP2K2:p.Arg179Trp, located in the protein kinase domain in the calf, and not found in more than 4500 control genomes including its sire. The identified variant affecting a conserved residue was predicted to be deleterious and most likely occurred de novo. This represents the first example of a dominant acting, and most likely pathogenic, variant in MAP2K2 in domestic animals, thereby providing the first MAP2K2-related large animal model, especially in respect to the enteric malformation. In addition, this study demonstrates the utility of WGS-based precise diagnostics for understanding sporadic congenital syndromic anomalies in cattle and the general utility of continuous surveillance for rare hereditary defects in cattle.Skeletal dysplasias encompass a clinical-, pathological- and genetically heterogeneous group of disorders characterized by abnormal cartilage and/or bone formation, growth, and remodeling. They may belong to the so-called RASopathies, congenital conditions caused by heterozygous variants in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) cell signaling pathway. Herein, an affected calf of the Italian Romagnola breed was reported showing a skeletal-cardio-enteric dysplasia. We identified a most likely disease-causing mutation in the MAP2K2 gene by whole-genome sequencing (WGS). The MAP2K2 gene is known to be related with dominant inherited cardio-facio-cutaneous syndrome in humans, but it was so far unknown to cause a similar disease in domestic animals. We assume that the identified missense variant that was predicted to impair the function of the protein, occurred either within the germline of the dam or post-zygotically in the embryo. Rare lethal diseases such as the skeletal-cardio-enteric dysplasia in livestock are usually not characterized to the molecular level, mainly because of the lack of funds and diagnostic opportunities. Precise WGS-based diagnostics enables the understanding of rare diseases and supports the value of monitoring cattle breeding populations for fatal genetic defects

Navel Healing and Calf Fitness for Transport

open5noDairy male calves are at risk of welfare compromise as they are usually transported at a very young age. The European Union has set a “completely healed navel” requirement for calf transport; moreover, a minimum age is established for longer journeys. However, this requirement has proven to be prone to misinterpretation. This study aimed to clarify what is meant by “navel healing” and to provide strong elements for reaching a consensus. The navels of 299 dairy calves (55 males, 244 females) aged 0–90 days were examined and scored 1 to 5 according to their healing status. Based on our results, a completely dry and shriveled navel (score 3) would imply a 25.5–38.0% risk of transporting too young calves. Alternatively, the presence of a scab covering the umbilical wound (score 4) would entail a 4.3% risk of transporting calves less than 10 days old and could be considered good practice for transporting calves (except for journeys exceeding 8 h). Conversely, complete navel healing (score 5) guarantees that calves that are too young are not transported; therefore, it should be considered best practice for transporting calves in general and the minimum requirement for transporting calves for journeys exceeding 8 h.openRoccaro, Mariana; Bolcato, Marilena; Masebo, Naod Thomas; Gentile, Arcangelo; Peli, AngeloRoccaro, Mariana; Bolcato, Marilena; Masebo, Naod Thomas; Gentile, Arcangelo; Peli, Angel

Associations between serum gamma-globulin concentration, enzyme activities, growth and survival in preweaning Alpine goat kids

Colostral immunity is crucial for young ruminants, but the individual factors that may affect passive transfer status and its effects on preweaning growth performance have not been widely investigated in goats. The methods to quantify immunoglobulins G can be expensive. Colostrum enzymes, though, pass the intestinal barrier and might be suitable as markers of passive transfer status, as demonstrated in other ruminant species. This study aimed to investigate the effect of sex, litter size, dam parity, and birth body weight on passive transfer status and the relationship between gamma-globulin concentration (GG) and pre-weaning growth performance in Alpine goat kids. The association between serum GG, serum total protein concentration and serum activity of colostrum enzymes including γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), aspartate aminotrans- ferase (AST), and lactate dehydrogenase (LDH) was examined for their use as predictors of passive transfer status in neonatal goat kids. Sixty-six Alpine goat kids (39 males, 27 females), born to 28 does at one dairy goat farm during two delivery seasons, were enrolled. Kids nursed their dams in group housing until weaned at 50 days of age. Blood samples were collected 24 h after birth. Body weights (BW) were taken at birth and weaning. Serum enzyme activities and total protein concentration were measured using a clinical biochemical analyser. Serum GG was determined by gel electrophoresis. Statistical analysis was performed using GraphPad Prism (v. 8.2.1). No significant differences in serum GG between males and females, singlets and twins, multiparous’ and pri- miparous’ kids were found. No association was detected between birth BW and GG. Serum GG was strongly and significantly associated with TP (R2 =0.85; p 0.0001) and moderately associated with GGT (R2 =0.47; p 0.0001). No correlation was found with ALP, AST, and LDH. Although partial failure of passive transfer (FPT) was diagnosed in 23% of kids, no effects on morbidity (3%), mortality (0%) and pre-weaning growth performance were observed. Our results confirm that serum total proteins can be used to indirectly estimate immunoglobulin concentration. Contrarily, passive transfer status can be predicted with little success by measuring the activity of serum GGT. It is not advisable to use ALP, AST and LDH as indicators of passive transfer status. Finally, FTP is not necessarily associated with the health and preweaning growth performance of Alpine goat kids reared in non- intensive breeding systems that follow good farming practices

Use of Electrodiagnostics in the Diagnosis and Follow-Up of Brachial Plexus Syndrome in a Calf

Electrodiagnostic testing by using electromyography (EMG) and nerve conduction studies (NCS) is essential in the evaluation of patients with traumatic brachial plexus injury as it facilitates the localization of the lesion and the prognosis. In this case report, we present a long-term electrodiag- nostic follow-up of a 5-day-old female Holstein calf with brachial plexus syndrome. Electrodiagnostic studies were carried out at 2 weeks, 5 weeks, 7 months and 12 months after admission. Initially, EMG confirmed the damage to the brachial plexus, potentially indicating a condition of neurotmesis or axonotmesis. However, motor NCS and the repeated electrodiagnostic follow-up, along with the evolution of the clinical signs, allowed a more favorable diagnosis of axonotmesis to be made. In fact, EMG showed a slow but gradual reduction and finally the disappearance of spontaneous pathological activity, while motor NCS revealed an increase in the amplitude and areas of the compound muscle action potentials. The animal was deemed fully recovered 12 months after admission. To the authors’ knowledge, this is the first report on the use of motor NCS in bovine medicine and it demonstrates that electrodiagnostics represent a useful and practical tool for the evaluation and prognosis of brachial plexus injury cases in cattle

A frameshift mutation in MOCOS is associated with familial renal syndrome (xanthinuria) in Tyrolean Grey cattle

[EN] Background: Renal syndromes are occasionally reported in domestic animals. Two identical twin Tyrolean Grey calves exhibited weight loss, skeletal abnormalities and delayed development associated with kidney abnormalities and formation of uroliths. These signs resembled inherited renal tubular dysplasia found in Japanese Black cattle which is associated with mutations in the claudin 16 gene. Despite demonstrating striking phenotypic similarities, no obvious presence of pathogenic variants of this candidate gene were found. Therefore further analysis was required to decipher the genetic etiology of the condition. Results: The family history of the cases suggested the possibility of an autosomal recessive inheritance. Homozygosity mapping combined with sequencing of the whole genome of one case detected two associated non-synonymous private coding variants: A homozygous missense variant in the uncharacterized KIAA2026 gene (g.39038055C > G; c.926C > G), located in a 15 Mb sized region of homozygosity on BTA 8; and a homozygous 1 bp deletion in the molybdenum cofactor sulfurase (MOCOS) gene (g.21222030delC; c.1881delG and c.1782delG), located in an 11 Mb region of homozygosity on BTA 24. Pathogenic variants in MOCOS have previously been associated with inherited metabolic syndromes and xanthinuria in different species including Japanese Black cattle. Genotyping of two additional clinically suspicious cases confirmed the association with the MOCOS variant, as both animals had a homozygous mutant genotype and did not show the variant KIAA2026 allele. The identified genomic deletion is predicted to be highly disruptive, creating a frameshift and premature termination of translation, resulting in severely truncated MOCOS proteins that lack two functionally essential domains. The variant MOCOS allele was absent from cattle of other breeds and approximately 4% carriers were detected among more than 1200 genotyped Tyrolean Grey cattle. Biochemical urolith analysis of one case revealed the presence of approximately 95% xanthine. Conclusions: The identified MOCOS loss of function variant is highly likely to cause the renal syndrome in the affected animals. The results suggest that the phenotypic features of the renal syndrome were related to an early onset form of xanthinuria, which is highly likely to lead to the progressive defects. The identification of the candidate causative mutation thus enables selection against this pathogenic variant in Tyrolean Grey cattleSIThis research received no specific grant from any funding agency in the public, commercial or non-profit sector

DYRK1B haploinsufficiency in a Holstein cattle with epilepsy.

In this study, epilepsy with focal seizures progressing to generalized seizures was diagnosed in a 6-month-old Holstein heifer. The seizures were characterized by a brief pre-ictal phase with depression and vocalization. During the ictal phase eyelid spasms, tongue contractions, nodding and abundant salivation were observed, rapidly followed by a convulsive phase with bilateral tonic, clonic or tonic-clonic activity and loss of consciousness. Finally, during the postictal phase the heifer was obtunded and disorientated, unable to perceive obstacles and hypermetric, and pressed its head against objects. In the inter-seizure phase, the heifer was clinically normal. Neuropathology revealed axonal degeneration in the brainstem and diffuse astrocytic hypertrophic gliosis. Whole genome sequencing of the affected heifer identified a private heterozygous splice-site variant in DYRK1B (NM_001081515.1: c.-101-1G>A), most likely resulting in haploinsufficiency owing to loss-of-function. This represents a report of a DYRK1B-associated disease in cattle and adds DYRK1B to the candidate genes for epilepsy

A Missense Variant in PLP2 in Holstein Cattle with X-Linked Congenital Mast Cell Tumor.

Congenital tumors occur infrequently in cattle. The aim of this study was to detail the clinicopathological phenotype of a Holstein calf with a congenital mast cell tumor and to identify the genetic cause by a whole-genome sequencing (WGS) trio-approach. An 18-day-old male Holstein calf was clinically examed and revealed multifocal, alopecic, thick and wrinkled skin lesions over the entire body. At 6 months of age, the general condition of the calf was characterized by retarded growth, poor nutritional status, and ulceration of the skin lesions. Histopathological examination revealed a primary cutaneous, poorly differentiated embryonal mast cell tumor with metastases in the lymph nodes and liver. Genetic analysis revealed a private X-linked variant in the PLP2 gene (chrX:87216480C>T; c.50C>T), which was present only in the genomes of the case (hemizygous) and his mother (heterozygous). It was absent in the sire as well as in 5365 control genomes. The identified missense variant exchanges the encoded amino acid of PLP2 at position 17 (p.Thr17Ile), which is classified as deleterious and affects a protein that plays a role in tumor growth and metastasis. Therefore, we suggested that the detected PLPL2 variant could be a plausible cause for this congenital condition in the affected calf

Differential Analysis of Gly211Val and Gly286Val Mutations Affecting Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA1) in Congenital Pseudomyotonia Romagnola Cattle.

Congenital pseudomyotonia in cattle (PMT) is a rare skeletal muscle disorder, clinically characterized by stiffness and by delayed muscle relaxation after exercise. Muscle relaxation impairment is due to defective content of the Sarco(endo)plasmic Reticulum Ca2+ ATPase isoform 1 (SERCA1) protein, caused by missense mutations in the ATP2A1 gene. PMT represents the only mammalian model of human Brody myopathy. In the Romagnola breed, two missense variants occurring in the same allele were described, leading to Gly211Val and Gly286Val (G211V/G286V) substitutions. In this study, we analyzed the consequences of G211V and G286V mutations. Results support that the reduced amount of SERCA1 is a consequence of the G211V mutation, the G286V mutation almost being benign and the ubiquitin-proteasome system (UPS) being involved. After blocking the proteasome using a proteasome inhibitor, we found that the G211V mutant accumulates in cells at levels comparable to those of WT SERCA1. Our conclusion is that G211/286V mutations presumably originate in a folding-defective SERCA1 protein, recognized and diverted to degradation by UPS, although still catalytically functional, and that the main role is played by G211V mutation. Rescue of mutated SERCA1 to the sarcoplasmic reticulum membrane can re-establish resting cytosolic Ca2+ concentration and prevent the appearance of pathological signs, paving the way for a possible therapeutic approach against Brody disease

Arachnomelia in Brown Swiss cattle maps to chromosome 5

Arachnomelia in Brown Swiss cattle is a monogenic autosomal recessive inherited congenital disorder of the skeletal system giving affected calves a spidery look (OMIA ID 000059). Over a period of 20years 15 cases were sampled in the Swiss and Italian Brown cattle population. Pedigree data revealed that all affected individuals trace back to a single acknowledged carrier founder sire. A genome scan using 240 microsatellites spanning the 29 bovine autosomes showed homozygosity at three adjacent microsatellite markers on bovine Chr 5 in all cases. Linkage analysis confirmed the localization of the arachnomelia mutation in the region of the marker ETH10. Fine-mapping and haplotype analysis using a total of 34 markers in this region refined the critical region of the arachnomelia locus to a 7.19-Mb interval on bovine Chr 5. The disease-associated IBD haplotype was shared by 36 proven carrier animals and allows marker-assisted selection. As the corresponding human and mouse chromosome segments do not contain any clear functional candidate genes for this disorder, the mutation causing arachnomelia in the Brown Swiss cattle might help to identify an unknown gene in bone developmen