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.     

Identification of mannosidosis heterozygotes — Factors affecting normal plasma α-mannosidase levels

Abstract

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Madam:— Thoracopagy, a condition in which equal and symmetrical twins are conjoined in or near their sternal regions ⁽³⁾ 1974. Dorland's Illustrated Medical Dictionary, 25th edition, 1604–1604. Philadelphia: W B Saunders Company.  [Google Scholar] and have hepatic and variable cardiac and gastrointestinal fusions, ⁽⁶⁾ Marin-Padilla, M., Chin, A.J., and Marin-Padilla, T.M. 1981. Cardiovascular abnormalities in thoracopagus twins. Teratology, 23: 101–113.  [Google Scholar] has been an uncommon cause of perinatal ovine mortalities. ⁽²⁾ Dennis, S.M. 1975. Embryonic duplications in sheep. Aust. vet. J., 51: 83–87.  [Google Scholar] ⁽⁴⁾ Hartley, W.J., and Kater, Joan. 1964. Perinatal disease conditions of sheep in New Zealand. N.Z. vet. J., 12: 49–57. [Taylor &; Francis Online] , [Google Scholar] ⁽⁸⁾ Roberts, S.J. 1971. Veterinary Obstetrics and genital diseases (Theriogenology), 73–80. Ithaca, New York: Published by the author.  [Google Scholar] Sheep are not mentioned in recent summaries of literature on detailed autopsy findings in thoracopagy. ⁽¹⁾ Czarnecki, C.M. and Schenk, M.P. 1977. A case of monster twinning (cephalothoracopagus) in the pig. Br. vet. J., 133: 530–534.  [Google Scholar] ⁽⁹⁾ Sekeles, E. 1985. Posterior duplication (cephalothoracopagus syncephalus) in the cat. Zbl. Vet. Med. A., 32: 793–799.  [Google Scholar] One other report ⁽¹⁰⁾ Sharma, M.M., and Mathur, D.B. 1980. A case report of ovine conjoined twins. Indian vet. J., 57: 88–89.  [Google Scholar] describes a pair of lambs with a common thorax and abdomen that contained disparate hearts and lungs and a single set of abdominal organs. We report autopsy findings in a pair of thoracopagus twin female lambs removed from a full-mouth Romney x Lincoln ewe which had been mated to a Lincoln ram.     

Enzootic bovine leukosis in New Zealand - A case report and update

Enzootic bovine leukosis was diagnosed in an year-old Friesian cow which had lost condition and was milking poorly. The cow had a severe nonregenerative anaemia, panhypoproteinaemia and lymphoid leukaemia. At necropsy there was widespread lymphoid infiltration of many organs, including the abomasal mucosa, myocardium, uterus, kidney, lymph nodes and bone marrow. Antibodies against bovine leukaemia virus were detected in the serum. Although clinical enzootic bovine leukosis is rare in New Zealand, having been confirmed on only five properties, infection with the causative agent, bovine leukaemia virus, is more widespread. The results of a recently completed survey of bulk milk samples using an enzyme-linked immunosorbent assay for bovine leukaemia virus antibodies suggest that there are about 300 dairy herds in the country with a bovine leukaemia virus infection level of at least 510%. The economic impact of enzootic bovine leukosis on the productivity of New Zealand's dairy cattle population is probably still negligible but the introduction of control or eradication schemes in Europe and North America could sooner or later lead to restrictions on the export of live cattle and genetic material from New Zealand.     

Osteochondrosis associated with copper deficiency in young farmed red deer and wapiti x red deer hybrids

Osteochondrosis is reported in association with copper deficiency in young red deer and wapiti x red deer hybrids on eight deer farms throughout New Zealand. On two farms, more than 30% of fawns were affected. Affected animals were lame, often had one or more swollen joints, and in some cases had an abnormal “bunny-hopping” gait or “cow-hocked” stance. Lesions were most common in the carpal, tarsal, stifle and hip joints, and were usually bilateral. Defects in articular cartilage ranged from loose flaps to complete separation with exposure of subchondral bone and the presence of cartilage fragments within the joint space. In advanced cases, the joints had features of degenerative arthropathy. Bilateral epiphyseolysis of the femoral head was observed in some severely lame deer. All deer with osteochondrosis had low serum and/or liver copper concentrations.     

Extreme neutrophilic leucocytosis and intrathoracic mass in a Fox Terrier

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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.     

Pathological changes in the lunS of a horse which had a history of intermittent nasal bleeding after exercise

A 4-year-old thoroughbred-cross gelding was presented with a history of intermittent nasal bleeding after exercise for the past 2 years.