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The clinical features of a newly recognised inherited disease, primary hyperoxaluria in the cat, are reported. Affected cats developed acute renal failure between five and nine months old owing to the deposition of oxalate crystals in the tubules of the kidney. In addition to the signs attributable to kidney failure the affected animals became profoundly weak; there was evidence of denervation atrophy in skeletal muscle, and accumulations of neurofilaments were found in the proximal axons of the ventral horn cells and dorsal root ganglion cells of the spinal cord. Examination of urine from affected cats revealed L-glyceric aciduria and intermittent hyperoxaluria suggesting that the disease is a feline analogue of the human disorder, primary hyperoxaluria type 2. This supposition was confirmed by liver enzyme studies.

Skeletal muscles from healthy dogs and Labrador Retrievers with hereditary muscular dystrophy were examined morphologically and histochemically and were analyzed biochemically for Na+, K+, Ca2+, Mg2+, Zn2+, Cu2+, Cl-, total muscle water, and total neutral lipid content. Flame atomic absorption spectrophotometer was used for elemental quantitation of hydrochloric acid tissue extracts. Muscle samples from dystrophic dogs contained substantially increased concentrations of Na+, Ca2+, Zn2+, Cu2+, and Cl-, and a considerable reduction in the content of K+ and Mg2+ compared with samples from healthy dogs. Total muscle water and total fat content was higher in muscles from dystrophic dogs. Most muscle samples from dystrophic dogs had a type-2 fiber deficiency and an increase in number of fibers with internalized nuclei.

Skeletal muscle and peripheral nerve were obtained over several years from 12 Labrador retrievers with signs of hereditary myopathy. Biopsy and necropsy samples were examined by histology and histochemistry. Despite normal findings in peripheral nerves, a wide range of morphologic changes were observed in muscle including features generally considered characteristic of neurogenic disease. These included small and large muscle fiber group atrophy, presence of small angular fibers, and occasional fiber type grouping. Other prominent changes in muscle were increased numbers of internal nuclei, architectural disturbances, type II fiber deficiency, necrosis, regeneration, and fibrosis--all of which are more usually associated with destructive myopathies or muscular dystrophies. The pathology of this condition, therefore, includes features of both neurogenic and myopathic disease, while the underlying pathophysiology remains unclear.

Protein profiles of whole homogenates of anconeus (slow twitch) and biceps femoris (fast twitch) muscles of clinically normal dogs and of Labrador Retrievers with hereditary myopathy (HM) were resolved on flat bed polyacrylamide isoelectric-focusing gels. Three methods of sample solubilization were performed. The solubilization buffer, with high concentrations of urea, precipitated the zwitterionic detergent, but use of the buffer containing 3% NP-40, 9.2M urea, and 0.1M arginine resulted in better resolution and stability of pH gradient. Gels of anconeus muscle from clinically normal dogs contained 2 protein bands specific to anconeus muscle, whereas gels of biceps femoris muscle from clinically normal dogs contained 3 protein bands amplified in biceps femoris muscle that were barely detectable in anconeus muscle. The staining intensity of protein bands in biceps femoris muscles from Labrador Retrievers with HM was decreased, relative to controls. The quantitative analysis of peak height ratios of biceps femoris muscle revealed significant (P less than 0.05) differences between profiles of clinically normal dogs and Labrador Retrievers with HM.

This paper concerns an enzymological investigation into a putative feline analogue of the human autosomal recessive disease primary hyperoxaluria type 2. The hepatic activities of D-glycerate dehydrogenase, using both D-glycerate and hydroxypyruvate as substrates, and glyoxylate reductase, which are the deficient enzyme activities in human primary hyperoxaluria type 2, were markedly depleted in four affected cats (0-6% of controls). The activities of a number of other enzymes, lactate dehydrogenase, glutamate dehydrogenase, D-amino acid oxidase, aspartate:2-oxoglutarate amino-transferase, glutamate:glyoxylate aminotransferase and alanine:glyoxylate aminotransferase (the deficient enzyme in primary hyperoxaluria type 1) were unaltered. The intracellular distribution of D-glycerate dehydrogenase and glyoxylate reductase in cat liver was shown to be cytosolic, as they are in human liver. The activities of D-glycerate dehydrogenase and glyoxylate reductase were determined in unaffected related cats and putative heterozygotes were identified. The correlation between D-glycerate dehydrogenase and glyoxylate reductase activities in the related cats and their combined deficiency in the affected cats confirmed previous suggestions that they are identical gene products.

Skeletal muscles from normal dogs and labrador retrievers with a hereditary muscular dystrophy were examined morphologically and histochemically and were analysed for sodium (Na+), potassium (K+) and chloride (Cl-) ions and total muscle water. The partition of total muscle water and electrolytes between intracellular and extracellular phases was calculated on the basis of the chloride space method as the estimate of extracellular fluid volume. Muscle samples from dystrophic dogs contained significantly increased concentrations of Na+, Cl-, total muscle water, and a significant reduction in the level of K+ compared with normal values. There was a significant increase in the intracellular water and Na+ levels with a concomitant reduction of intracellular K+ content. Most dystrophic muscle samples had a pronounced type 2 fibre deficiency and a marked increase in numbers of fibres with internalised nuclei.

Morphometric analysis was carried out on electron micrographs of motor endplates from three Jack Russell terriers affected with congenital myasthenia gravis (CMG) aged 10 weeks, 12 weeks and 22 weeks, respectively. Control endplates from age-matched pups and an adult Jack Russell were also examined. The results showed that postsynaptic membrane density was significantly increased in affected animals and secondary fold length was decreased. The ratio of postsynaptic to presynaptic membrane length was normal in the 10 and 12-week-old pups, but reduced in the 22-week-old CMG animal. These changes were unrelated to muscle fibre diameter and there was no evidence of a destructive process. It is suggested that the alteration in membrane folding pattern in this condition may be related to abnormal trophic influences during synaptogenesis.