Inherited chondrodysplasia in Texel sheep

CASE HISTORY: A skeletal disease characterised by dwarfism, limb deformity and sometimes sudden death occurred over a period of 5 years in lambs born on a commercial sheep farm in Southland. The disease showed variable expression and occurred in crossbred sheep. A genetic aetiology was supported by the birth of affected lambs over two seasons in a flock of putative carrier and affected sheep transported to Massey University.

CLINICAL FINDINGS: Affected lambs appeared normal at birth but showed evidence of dwarfism, wide-based stance and exercise intolerance as early as 1 week of age. Most died within the first 3 months of life, often after developing bilateral varus deformity of the forelimbs. Some severely-affected lambs died suddenly of respiratory embarrassment, probably due to tracheal collapse. Mildly-affected individuals had a short, blocky stature and some survived to breeding age.

PATHOLOGICAL FINDINGS: Gross and microscopic lesions of variable severity were present in the tracheal, articular, epiphyseal and physeal cartilages. In severe cases, articular cartilage in major joints was eroded from weight-bearing surfaces. The trachea was flaccid, abnormally kinked, and had thickened cartilaginous rings and a narrow lumen. Affected sheep that survived to breeding age eventually developed severe degenerative joint disease. Histologically, chondrocytes were disorganised, surrounded by concentric rings of abnormal fibrillar material, and the matrix often contained focal to coalescing areas of chondrolysis.

DIAGNOSIS: Inherited chondrodysplasia of Texel sheep.

CLINICAL RELEVANCE AND CONCLUSIONS: This chondrodysplasia differs from those previously described in sheep and is considered to be a newly-recognised, recessively-inherited genetic disease of the Texel breed. A defect in the synthesis of glycosaminoglycans in cartilage matrix is suspected. This disease of sheep may provide a suitable model for studying various forms of therapy for human chondrodysplasias.     

Finding the mutation responsible for inherited rickets in Corriedale sheep

Inherited rickets of Corriedale sheep is of simple autosomal recessive inheritance. The gross and histological lesions include segmental thickening of physes, persistence of hypertrophic chondrocytes at sites of endochondral ossification, excessive osteoclastic resorption, microfractures and wide unmineralised osteoid seams lining trabeculae and filling secondary osteons. Initial testing revealed concentrations of 25-hydroxyvitamin D₃ were normal, but those of 1,25-dihydroxyvitamin D₃ were increased in serum of affected sheep, suggesting a defect in the vitamin D receptor. However, in vitro studies on cultured skin fibroblasts revealed normal binding and function of the vitamin D receptor.

A genome-wide association study was conducted using the Illumina OvineSNP50 BeadChip. A homozygous region of 199 consecutive single-nucleotide polymorphism loci was identified in affected sheep, covering a region of 10 megabase pairs on ovine chromosome 6. Of the 91 candidate genes in this region, dentin matrix protein 1 gene (dmp1) was considered the most likely as it is known to play critical roles in osteocyte maturation and mineral metabolism. Sequencing of DNA from carriers showed a nonsense mutation 253T/C in dmp1. This T/C transition introduced a stop codon (R145X) that could truncate C-terminal amino acids. Using PCR restriction fragment length polymorphism for this mutation, genotyping showed that all affected sheep were “TT” genotypes, and phenotypically normal sheep were either “CT” or “CC”. These findings suggest that a mutation in dmp1 is responsible for inherited rickets of Corriedale sheep. A simple diagnostic test is currently being designed to identify carriers with the defective “T” alleles.     

Extreme neutrophilic leucocytosis and intrathoracic mass in a Fox Terrier

Extract

An 8-year-old female Fox Terrier was presented for acute anorexia and depression. A haemogram revealed extreme neutrophilic leucocytosis (136×10⁹/L neutrophils). By Day 4, the neutrophilia was more marked (214×10⁹/L segmented; 23×10⁹/L band). Imaging revealed a cranial mediastinal mass, pleural effusion and small pneumothorax. Needle aspiration of the mass showed cells resembling malignant histiocytes against a background of mature neutrophils. On Day 7, the mass was surgically removed. Histologically, it revealed a malignancy suggestive of histiocytic sarcoma intensely infiltrated with neutrophils. Immunocyto-chemical investigations are pending. Post-operatively, the dog's appetite and demeanour improved but breathing was laboured, and neutrophilia persisted (300×10⁹/L on Day 14). The dog was humanely killed on Day 14; post mortem examination revealed no distant metastases. This dog's illness is strongly reminiscent of a rare human condition, inflammatory malignant fibrous his-tiocytoma with leukaemoid reaction (IMFH-LR). In IMFH-LR, neoplastic cells produce cytokines that attract neutrophils to the tumour. Other cytokines stimulate the bone marrow to produce extreme neutrophilia. Although paraneoplastic neutrophilia has previously been described in dogs, this is an extreme example and the condition has not previously been associated with histiocytic or intrathoracic malignancies.     

Impact of dung from ivermectin-treated sheep on oogenesis and survival of adult Lucilia cuprina

Females of the Australian sheep blowfly, Lucilia cuprina, exploit sheep dung as a source of protein for egg development. Flies fed on dung collected from sheep 1 to 6 days after being drenched with the broad-spectrum antiparasitic drug ivermectin showed delayed reproductive development and reduced fecundity. Male and female survival was also reduced. Despite these effects, except where the recommended frequency of drenching (1 to 4 times per annum) is greatly exceeded, it is unlikely that ivermectin residues will affect any useful reduction in blowfly populations.     

A lymphoproliferative disease in Manx cats with similarities to autoimmune lymphoproliferative syndrome (ALPS) in people

In 2009–2010, an unusual lymphoproliferative disease was identified in multiple siblings from successive litters of Manx cats, suggesting a genetic predisposition to development of this disease. Presentation of disease in the cats had multiple similarities with the human disease ALPS, a rare inherited disorder that causes persistent lymphoproliferation, together with variable manifestations of autoimmunity and increased susceptibility to neoplasia. The majority of human ALPS patients have inherited Fas gene mutations, causing defective apoptosis of lymphocytes, although for a proportion of ALPS patients the underlying genetic mutations remain unknown. In order to identify the likely mode of inheritance of the disease, further matings of potential carrier cats are in progress. Studies to investigate the potential role of abnormalities in the Fas gene in the development of the disease in cats are also proposed. Identifying and further characterising the nature and mechanism of the disease in cats may allow better understanding of the development, progression, and treatment of ALPS in humans.     

Seasonal variation in the hip score of dogs as assessed by the New Zealand Veterinary Association Hip Dysplasia scheme

Abstract

AIM: To determine whether there is a seasonal variation in the phenotypic hip score of dogs born in New Zealand as assessed by the New Zealand Veterinary Association (NZVA) canine hip dysplasia (CHD) scheme.

METHODS: Data from dogs born in New Zealand between 1988 and 2009 that have been scored for CHD were retrospectively evaluated for the effect of month of birth on radiographic phenotype. Data included both the total score and the subtotal score, comprising Norberg's angle, the subluxation score and changes to the cranial acetabular edge, for each dog. Datasets were created for all breeds combined and for the four most populous breeds using the scheme (German Shepherd dog, Labrador Retriever, Golden Retriever and Rottweiler) and stratified according to month of birth and season. Due to the skewed nature of the data, a Kruskal–Wallis Rank Sum test was used to test for statistical significance. Additionally, χ² analysis was performed using the median of each dataset (proportion above/below the median). The null hypothesis was that there would be no effect of month of birth, and hence seasonality, on hip phenotype for dogs born and scored in New Zealand by the NZVA.

RESULTS: For all breeds combined, month of birth had an effect on total and subtotal NZVA CHD scores (p<0.001) with a lower total hip score in the autumn months of March and April than other months. When individual large breed data were analysed, there was an effect of month of birth on total and subtotal scores for the Labrador Retriever and the Rottweiler (p≤0.05), but not the German Shepherd dog or Golden Retriever breeds.

CONCLUSIONS: Being born in the autumn was associated with a protective effect on hip phenotype in some breeds. These results suggest that weather and/or another seasonal factor may have a significant environmental effect on the phenotype of the coxofemoral joint.

CLINICAL RELEVANCE: The protective effect of being born in autumn suggests that a decreased level of exercise during subsequent development over winter may positively impact on final coxofemoral joint conformation. Whilst statistically significant, the magnitude of the sparing effect is not likely to be clinically relevant. However, this study, in concert with other studies, may suggest that the effects of exercise can be manipulated to improve hip phenotype.     

Osseous lesions resembling vaccine-site sar comas in two cats

Extract

Lytic lesions with microscopic features similar to those of vaccine-site sarcomas were diagnosed in the distal femur of two young neutered male cats, one a 20-month-old Birman and the other an 18-month-old domestic short-hair (DSH). Radiographically, there was extensive destruction of trabecular and cortical bone in the metaphysis and/or epiphysis of the distal femur. The DSH cat also had angular deformity of the distal femur due to asymmetrical involvement of the physis. Histologically, the lesions in both cats consisted of dense, interwoven bundles of fibrous connective tissue, amongst which there were variable numbers of plump malignant mesenchymal cells, often with very large, hyperchromatic nuclei and irregularly shaped nucleoli. Several focal aggregates of small lymphocytes were present in both tumours. Although neither cat had apparently been vaccinated in the hindlimb it is possible that the tumours had been triggered by injection of some other irritant material.