Chondrodysplasia of Texel sheep : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand
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Date
2008
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Massey University
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Abstract
Chondrodysplasia of Texel sheep is a newly described recessively inherited disorder
distinct from other chondrodysplasias described in sheep. Phenotypically normal
at birth, affected lambs develop microscopic lesions as early as 9 days of age, and
usually demonstrate gross deformities and markedly reduced rates of bone growth
by 2 to 3 weeks. Individual bone growth rates are most severely affected in the
proximal bones of the forelimbs. Chondrodysplastic lambs typically have short
stature, angular limb deformities, a barrel-shaped chest and a wide-based stance.
Gross lesions include tracheal narrowing and contortion, enlarged costochondral
junctions, and erosion of articular cartilage in major limb joints. Microscopic
lesions are confined to hyaline cartilage, and are characterised by degeneration of
the interterritorial matrix and dense perichondrocytic rings consisting
predominantly of type VI collagen. These lesions are identical in appearance to
those in achondrogenesis 1b and diastrophic dysplasia, two diseases caused by
defects of the diastrophic dysplasia sulphate transporter (DTDST) in human beings.
An investigation to measure the uptake of radiolabelled sulphate by dermal
fibroblasts in vitro did not provide evidence of a defect in the DTDST in
chondrodysplastic Texel sheep. A linkage disequilibrium study of ovine
chromosomes 1, 5, 6, 13 and 22 using microsatellite DNA markers was unable to
identify evidence of a mutation causing this form of chondrodysplasia. Capillary
electrophoresis of unsaturated chondroitin sulphate disaccharides demonstrated a
relative reduction in the ratio of chondroitin 4-sulphate to chondroitin 6-sulphate
in affected animals of all ages. This biochemical feature enables the potential
determination of the phenotype of newborn lambs prior to the emergence of gross
or microscopic lesions.
The pathology of the disease, combined with the findings of the genetic,
biochemical and in vitro studies, suggest that a mutation may be present in the
CHST11 gene. This gene is a good candidate for future studies aimed at discovering
the genetic defect in chondrodysplasia of Texel sheep and developing a test to
identify heterozygous animals.
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Keywords
Chondrodysplasia, Texel sheep, Genetic defects, Inherited diseases