GM2 gangliosidosis in British Jacob sheep.

GM2 gangliosidosis (Tay-Sachs disease) was diagnosed in 6- to 8-month-old pedigree Jacob lambs from two unrelated flocks presenting clinically with progressive neurological dysfunction of 10 day's to 8 week's duration. Clinical signs included hindlimb ataxia and weakness, recumbency and proprioceptive defects. Histopathological examination of the nervous system identified extensive neuronal cytoplasmic accumulation of material that stained with periodic acid--Schiff and Luxol fast blue. Electron microscopy identified membranous cytoplasmic bodies within the nervous system. Serum biochemistry detected a marked decrease in hexosaminidase A activity in the one lamb tested, when compared with the concentration in age matched controls and genetic analysis identified a mutation in the sheep hexa allele G444R consistent with Tay-Sachs disease in Jacob sheep in North America. The identification of Tay-Sachs disease in British Jacob sheep supports previous evidence that the mutation in North American Jacob sheep originated from imported UK stock.

Identification of congenital muscular dystonia 2 associated with an inherited GlyT2 defect in Belgian Blue cattle from the United Kingdom.

Two newborn Belgian Blue calves from a farm in the United Kingdom exhibited lateral recumbency, low head carriage and transient muscle spasms following tactile or auditory stimulation. DNA sequence analysis indicated that both calves were homozygous for the recessive congenital muscular dystonia type 2 (CMD2) mutation (c.809T>C, p.Leu270Pro) in SLC6A5, encoding the neuronal glycine transporter GlyT2. Further testing of animals from the index farm and a sample of Belgian Blue sires revealed an unexpectedly high frequency of CMD2 carriers. This implies that linked quantitative trait loci may be influencing the prevalence of CMD2 in the estimated 55,000 Belgian Blue cattle in the United Kingdom. We have therefore developed new inexpensive tests for the CMD2 allele that can be used to confirm diagnosis, identify carriers and guide future breeding strategy, thus avoiding animal distress/premature death and minimizing the future economic impact of this disorder.

Increased immunohistochemical labelling for prion protein occurs in diverse neurological disorders of sheep: relevance for normal cellular PrP function.

The classical prion diseases (e.g. scrapie of sheep and goats and bovine spongiform encephalopathy of cattle) are characterized by the accumulation of abnormal forms of the prion protein (PrP), usually recognized by their relative resistance to proteolysis compared with the physiological cellular forms of PrP. However, novel prion diseases have been detected in sheep, cattle and man, in which the abnormal PrP has less resistance to proteolysis than identified previously. These more subtle differences between abnormal and normal forms of PrP can be problematic in routine diagnostic tests and raise questions in respect of the range of PrP disorders. Abnormal accumulations of PrP in atypical and classical prion diseases can be recognized by immunohistochemistry. To determine whether altered PrP expression or trafficking might occur in nosological entities not previously connected with prion disease, the brains of sheep affected with diverse neurological conditions were examined for evidence of altered PrP labelling. Such altered immunolabelling was detected in association with either basic lesions or specific diseases. Some reactive glial cells and degenerate neurons found in several different recognized disorders and non-specific inflammatory processes were associated with abnormal PrP labelling, which was absent from brains of healthy, age-matched sheep. The results agree with previous indications that normal PrP function may be linked with the oxidative stress response, but the data also suggest that PrP functions are more extensive than simple protective responses against stress insults.

Clinical, ultrasonographic and pathological findings in a bull with segmental aplasia of the mesonephric duct.

On assessment for use in an AI stud, a 12-month-old bull was found to produce low volume ejaculates with 41% of the sperm having morphological abnormalities. No left epididymal tail was palpable and the head of the epididymis on the left was twice the size compared with the right. Ultrasound examination showed the left testis to contain a large central area of decreased echogenicity, which could be followed proximally to a 15-mm echolucent lesion at the site of the epididymal head. Postmortem examination revealed a 15-mm diameter cyst in the region of the left epididymal head, and absence of the body and tail of the epididymis. The mediastinum testis of the left testis was dilated, corresponding to the area of decreased echogenicity observed on ultrasonography. No left seminal vesicle was present and the ampulla was significantly smaller than the same structure on the right. Histological examination revealed incomplete or absent spermatogenesis involving the majority of seminiferous tubules in the left testis, and a small proportion of those of the right testis. The cystic structure at the site of the left epididymal head was lined by irregular, sometimes attenuated, epithelium and contained sparse spermatozoa. This case demonstrates the adverse impact, which segmental aplasia of the mesonephric duct had on the testicular and epididymal function of a bull, and highlights the importance of careful clinical assessment in its diagnosis.

Congenital tremor and hypomyelination associated with bovine viral diarrhoea virus in 23 British cattle herds.

This paper presents data from 23 British herds investigated between 1991 and 2007 where neurological disease in calves was caused by bovine viral diarrhoea virus (BVDV) infection. A variety of clinical signs, most commonly tremor or trembling, were apparent in the calves from birth, and most were recumbent or unable to stand unsupported. Severe diffuse neuraxial hypomyelination was present in all of the calves, and immunohistochemistry revealed cerebral neuronal labelling consistent with congenital persistent pestivirus infection in each brain. BVDV was detected in peripheral blood samples from eight of 15 calves tested using an antigen ELISA, and was isolated in culture from samples of viscera, brain or blood collected from 17 of 24 affected calves. TaqMan RT-PCR for pestivirus RNA was positive for BVDV-1 in all six calves tested. Six of the virus isolates on which molecular classification was carried out, obtained from calves in four of the herds, were identified as BVDV-1a, while three isolates from one affected and two unaffected calves on a fifth farm were confirmed as BVDV-1b.

Critical assessment of an in vitro bovine respiratory organ culture system: a model of bovine herpesvirus-1 infection.

A bovine in vitro organ culture (BIVOC) system was evaluated as a model to study host and pathogen events during the course of bovine herpesvirus-1 infection. Upper respiratory tract epithelium, from slaughtered animals, was cultured in an air-liquid interface system and integrity, viability, and TNF-alpha gene expression of tissue explants were monitored over 72h in the presence or absence of infection by bovine herpesvirus type 1 (BHV-1). Uninfected explants maintained viability and integrity over the 72h time course although histological signs of degeneration were first visible from 24h of culture. Explants were productively infected with BHV-1 and typical, dose dependent, cytopathic changes were observed in response to infection. Regulation of TNF-alpha gene expression in uninfected explants varied over time and was region-specific but there was significant down-regulation of TNF-alpha gene expression at 2h post-infection when compared to uninfected controls at the same time point. Taking caveats into consideration the BIVOC system shows promise as a tool for analysis of immediate or early events in host-pathogen interaction.

Cerebral segmental polyarteritis of unknown aetiology in sheep.

Vasculitis affecting the meningeal elastic arteries was identified in six sheep of various breeds during routine diagnostic investigation. The lesions consisted of multifocal intimal proliferation, thickening of the tunica media, multifocal infiltration of the media by inflammatory cells and more extensive perivascular accumulation of lymphocytes and plasma cells within the tunica adventitia. Fibrinoid necrosis affected an intergyral artery in one sheep. Immunohistochemistry failed to demonstrate pestivirus antigen associated with the lesions and no alternative aetiology was defined. Possible causes of meningeal segmental polyarteritis in sheep are discussed.

Ulcerative vulvitis and balanitis in sheep flocks.

Outbreaks of ulcerative vulvitis and balanitis occurred in three commercial sheep flocks in England and Wales. Between 29 and 44 per cent of the ewes were affected; most of the lesions resolved in three weeks. Pathogens such as mycoplasmas, which have previously been associated with these conditions, were not detected despite using improved laboratory techniques. In one of the flocks, ovine herpesvirus type 2 was detected by pcr in the blood of two acutely affected ewes, from the vulval ulcers of one of them, and from the penis of an affected ram.