Transmission of Norwegian reindeer CWD to sheep by intracerebral inoculation results in an unusual phenotype and prion distribution.

Chronic wasting disease (CWD), a prion disease affecting cervids, has been known in North America (NA) since the 1960s and emerged in Norway in 2016. Surveillance and studies have revealed that there are different forms of CWD in Fennoscandia: contagious CWD in Norwegian reindeer and sporadic CWD in moose and red deer. Experimental studies have demonstrated that NA CWD prions can infect various species, but thus far, there have been no reports of natural transmission to non-cervid species.

Intestinal strangulation in farmed Atlantic cod (Gadus morhua): Pathological changes and possible predisposing anatomical features.

During recent years, there has been a renewed interest in establishing farming of Atlantic cod (Gadus morhua) in Norway. However, a fatal abdominal disorder compromises animal welfare and causes economic losses. A similar problem was present during a previous attempt to establish Atlantic cod farming more than a decade ago.

Femoral Nailing in a Porcine Model Causes Bone Marrow Emboli in the Lungs and Systemic Emboli in the Heart and Brain.

Background: Shaft fractures of the femur are commonly treated with intramedullary nailing, which can release bone marrow emboli into the bloodstream. Emboli can travel to the lungs, impairing gas exchange and causing inflammation. Occasionally, emboli traverse from the pulmonary to the systemic circulation, hindering perfusion and resulting in injuries such as heart and brain infarctions, known as .

CO Stunning in Pigs: Physiological Deviations at Onset of Excitatory Behaviour.

Stunning by carbon dioxide (CO) inhalation is controversial because it is associated with vigorous movements and behaviours which may or may not be conscious reactions. Furthermore, it is unknown whether some behaviours might indicate the transition into unconsciousness. Our study objective was to investigate the loss of consciousness during CO stunning by linking physiological variables (in particular pH, PaO and PaCO) to the onset of observed behaviours.

No evidence of uptake or propagation of reindeer CWD prions in environmentally exposed sheep.

Background: Chronic wasting disease (CWD) is a prion disease of cervids first reported in North America in the 1960s. In Europe, CWD was first diagnosed in 2016 in a wild reindeer in Norway. Detection of two more cases in the same mountain area led to the complete culling of this partially confined reindeer population of about 2400 animals.

A 1 bp deletion in HACE1 causes ataxia in Norwegian elkhound, black.

A number of inherited ataxias is known in humans, with more than 250 loci implicated, most of which are included in human ataxia screening panels. Anecdotally, cases of ataxia in the Norwegian elkhound black have been known for the last 40 years. Affected puppies from three litters were clinically and neurologically examined, and postmortem samples were collected for morphological studies, including ultrastructural analyses.

Tongue atrophy as a neurological finding in hereditary polyneuropathy in Alaskan malamutes.

Background: Tongue atrophy with wrinkling as a clinical sign of inherited polyneuropathies has not been reported in dogs.

Objectives: Clinically describe tongue atrophy as well as morphology of the tongue and hypoglossal nerve in Alaskan malamute polyneuropathy (AMPN).

Animals: Six client-owned Alaskan malamute dogs diagnosed with AMPN, all homozygous for the causative mutation in the N-myc downstream-regulated gene 1 (NDRG1) and 1 neurologically normal control Alaskan malamute.

Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D.

Mutations in the N-myc downstream-regulated gene 1 (NDRG1) cause degenerative polyneuropathy in ways that are poorly understood. We have investigated Alaskan Malamute dogs with neuropathy caused by a missense mutation in NDRG1. In affected animals, nerve levels of NDRG1 protein were reduced by more than 70% (p< 0.

Goats naturally devoid of PrP are resistant to scrapie.

Prion diseases are progressive and fatal, neurodegenerative disorders described in humans and animals. According to the "protein-only" hypothesis, the normal host-encoded prion protein (PrP) is converted into a pathological and infectious form (PrP) in these diseases. Transgenic knockout models have shown that PrP is a prerequisite for the development of prion disease.

Demyelinating polyneuropathy in goats lacking prion protein.

Studies in mice with ablation of Prnp, the gene that encodes the cellular prion protein (PrP ), have led to the hypothesis that PrP is important for peripheral nerve myelin maintenance. Here, we have used a nontransgenic animal model to put this idea to the test; namely, goats that, due to a naturally occurring nonsense mutation, lack PrP . Teased nerve fiber preparation revealed a demyelinating pathology in goats without PrP .

Cell and context-dependent sorting of neuropathy-associated protein NDRG1 - insights from canine tissues and primary Schwann cell cultures.

Background: Mutations in the N-myc downstream-regulated gene 1 (NDRG1) can cause degenerative polyneuropathy in humans, dogs, and rodents. In humans, this motor and sensory neuropathy is known as Charcot-Marie-Tooth disease type 4D, and it is assumed that analogous canine diseases can be used as models for this disease. NDRG1 is also regarded as a metastasis-suppressor in several malignancies.

Neuronal ceroid lipofuscinosis in Salukis is caused by a single base pair insertion in CLN8.

Neuronal ceroid lipofuscinoses (NCLs) are heterogenic inherited lysosomal storage diseases that have been described in a number of species including humans, sheep, cattle, cats and a number of different dog breeds, including Salukis. Here we present a novel genetic variant associated with the disease in this particular breed of dog. In a clinical case, a Saluki developed progressive neurological signs, including disorientation, anxiety, difficulties in eating, seizures and loss of vision, and for welfare reasons, was euthanized at 22 months of age.

Stress Resilience of Spermatozoa and Blood Mononuclear Cells without Prion Protein.

The cellular prion protein PrP is highly expressed in neurons, but also present in non-neuronal tissues, including the testicles and spermatozoa. Most immune cells and their bone marrow precursors also express PrP. Clearly, this protein operates in highly diverse cellular contexts.

Goats without Prion Protein Display Enhanced Proinflammatory Pulmonary Signaling and Extracellular Matrix Remodeling upon Systemic Lipopolysaccharide Challenge.

A naturally occurring mutation in the gene of Norwegian dairy goats terminates synthesis of the cellular prion protein (PrP), rendering homozygous goats () devoid of the protein. Although PrP has been extensively studied, particularly in the central nervous system, the biological role of PrP remains incompletely understood. Here, we examined whether loss of PrP affects the initial stage of lipopolysaccharide (LPS)-induced acute lung injury (ALI).

Loss of prion protein induces a primed state of type I interferon-responsive genes.

The cellular prion protein (PrPC) has been extensively studied because of its pivotal role in prion diseases; however, its functions remain incompletely understood. A unique line of goats has been identified that carries a nonsense mutation that abolishes synthesis of PrPC. In these animals, the PrP-encoding mRNA is rapidly degraded.

LPS-induced systemic inflammation reveals an immunomodulatory role for the prion protein at the blood-brain interface.

Background: The cellular prion protein (PrP) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrP (PRNP ) provides a novel model for studying PrP physiology.

Methods: In order to explore putative roles for PrP in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP and 8 PRNP ) and included 10 saline-treated controls (5 of each PRNP genotype).

Re-emergence of hereditary polyneuropathy in Scandinavian Alaskan malamute dogs-old enemy or new entity? A case series.

A homozygous mutation has been identified in the N-myc downstream-regulated gene 1 (NDRG1) in recent cases of polyneuropathy in Alaskan malamute dogs from the Nordic countries and USA. The objective of the present study was to determine if cases diagnosed 30-40 years ago with polyneuropathy in the Alaskan malamute breed in Norway had the same hereditary disease as the recent cases. Fourteen historical cases and 12 recently diagnosed Alaskan malamute dogs with hereditary polyneuropathy, and their parents and littermates (n = 88) were included in this study (total n = 114).

Activation of innate immune genes in caprine blood leukocytes after systemic endotoxin challenge.

Background: Sepsis is a serious health problem associated with a range of infectious diseases in animals and humans. Early events of this syndrome can be mimicked by experimental administration of lipopolysaccharides (LPS). Compared with mice, small ruminants and humans are highly sensitive to LPS, making goats valuable in inflammatory models.

NCR1+ cells appear early in GALT development of the ovine foetus and acquire a c-kit+ phenotype towards the end of gestation.

The amount, distribution and phenotype of ovine NCR1+ cells were investigated during developing GALT from day 70 of gestation. Antibodies against CD3 and CD79 were used to identify the compartments of GALT, and the localization of NCR1+ cells were correlated within these structures. Markers CD34 and c-kit, in addition to Ki67, were used to investigate possible origin and the stage of development of the NCR1+ cells.

The Cellular Prion Protein: A Player in Immunological Quiescence.

Despite intensive studies since the 1990s, the physiological role of the cellular prion protein (PrP(C)) remains elusive. Here, we present a novel concept suggesting that PrP(C) contributes to immunological quiescence in addition to cell protection. PrP(C) is highly expressed in diverse organs that by multiple means are particularly protected from inflammation, such as the brain, eye, placenta, pregnant uterus, and testes, while at the same time it is expressed in most cells of the lymphoreticular system.

Hematological shift in goat kids naturally devoid of prion protein.

The physiological role of the cellular prion protein (PrP(C)) is incompletely understood. The expression of PrP(C) in hematopoietic stem cells and immune cells suggests a role in the development of these cells, and in PrP(C) knockout animals altered immune cell proliferation and phagocytic function have been observed. Recently, a spontaneous nonsense mutation at codon 32 in the PRNP gene in goats of the Norwegian Dairy breed was discovered, rendering homozygous animals devoid of PrP(C).

The early intestinal immune response in experimental neonatal ovine cryptosporidiosis is characterized by an increased frequency of perforin expressing NCR1(+) NK cells and by NCR1(-) CD8(+) cell recruitment.

Cryptosporidium parvum, a zoonotic protozoan parasite, causes important losses in neonatal ruminants. Innate immunity plays a key role in controlling the acute phase of this infection. The participation of NCR1+ Natural Killer (NK) cells in the early intestinal innate immune response to the parasite was investigated in neonatal lambs inoculated at birth.

Glomerular Collagen V Codeposition and Hepatic Perisinusoidal Collagen III Accumulation in Canine Collagen Type III Glomerulopathy.

Collagen type III glomerulopathy, also known as collagenofibrotic glomerulopathy, is a rare renal disease of unknown pathogenesis. The disease occurs in humans and animals and is characterized by massive glomerular accumulations of collagen type III. In the present study, we describe a Drever dog litter affected by an early onset variant of this glomerular disease, where 4 of 9 puppies developed renal failure within 50 days of age.

Yessotoxin triggers ribotoxic stress.

This work tests the hypothesis that the marine algal toxin yessotoxin (YTX) can trigger ribotoxic stress response in L6 and BC3H1 myoblast cells. YTX exposure at a concentration of 100 nM displays the characteristics of a ribotoxic stress response in such cells. The exposure leads to activation of the p38 mitogen-activated protein kinase, the stress-activated protein kinase c-jun, and the double-stranded RNA-activated protein kinase (PKR).