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Development of the ovine model of NCL has been pivotal to our present understanding of the ceroid lipofuscinoses. Analyses of isolated storage product have shown it to be composed of identifiable chemical species of which subunit c of mitochondrial ATP synthase is dominant (ca 50 %). It is an extremely hydrophobic protein and failure to catabolise it may be associated with a propensity to form paracrystalline structures with lipids that cannot be degraded by the normal complement of lysosomal enzymes. However, the putative biochemical defect must be related to it and may reside within the mitochondria. Multiple copies of subunit c help form the transmembrane Fo complex which, with partially immobilised lipids, forms an FO COMPLEX DOMAIN. This may need to be disassembled in an orderly fashion before proteolysis of subunit c can occur. It is postulated that the primary defect may involve disassembly of the FO COMPLEX DOMAIN which may involve more than one step.

The lipopigments are a heterogenous group of pigments whose pathogenesis and terminology is confused. Whereas there is epidemiological and observational evidence that ceroid is derived from degeneration and peroxidation of unsaturated lipid, the assumption that all so-called lipopigments are similarly formed, is questioned. In particular, recent studies have distanced the pathogenesis of the pigment found in the ceroid-lipofuscinoses from that perceived for ceroid. The importance of protein rather than lipid in the pathogenesis of the pigment of ceroid-lipofuscinosis and of age pigment from the equine thyroid is noted. In the former the essential feature is storage of the DCCD binding protein subunit c of mitochondrial ATP synthase. There is a need for more analytical studies on isolated pigments which are generally more soluble than anticipated by the literature. It is proposed that the term ceroid be limited to a family of pathological pigments where lipid degeneration and peroxidation is implied from observational and/or epidemiological factors. The term age pigment is unequivocal and preferred for age related pigment not obviously complicated by other factors. The terms lipofuscin and lipopigment retain a usefulness as generic terms, particularly where the nature of the pigment is uncertain. The term ceroid-lipofuscinosis for the inherited storage diseases of children and animals is misleading. The term "proteolipid proteinosis" has been suggested to define this group of diseases but this is perhaps premature until their full pathogenesis is known.

Extract Mannosidosis is an inherited neurological disease of Angus calves associated with a deficiency of lysosomal α-mannosidase (Hocking et al., 1972). The disease can now be controlled through the ability to recognize heterozygous individuals that have less than half the normal levels of plasma α-mannosidase activity (Jolly et al., 1973; 1974a). As a consequence a test and control program, has been developed within the Angus bult-breeding herds of New Zealand, to be run by the Ministry of Agriculture and Fisheries in conjunction with the New Zealand Angus Association (Jolly et al., 1974b,c). Because various factors may influence plasma α-mannosidase activity, it is necessary to analyse results within relatively homogeneous age, sex and mob groups on the one property (Jolly et al., 1974a and unpublished data). In most groups there will be a small overlap area which, includes animals with high heterozygous and low normal values. Designation of the genotype of individuals in this area may be faci...

Extract Recent research has shown that the gene frequency for mannosidosis (pseudolipidosis) may approximate 0.05 in pedigree Angus herds (Jolly, unpublished data). As epidemiological studies suggest an equal frequency in commercial non-pedigree herds, the disease is elf economic importance to the national beef industry. Mannosidosis is an inherited lysosomal storage disease associated with a defect in catabolism, of the heterosaccharide fractioln of glycoproteins (Whittem and Walker, 1957; Jolly 1971; Hocking et al., 1972; Phillips et al., 1974). Whereas animals with mannosidosis have negligible tissue sand plasma levels of α-mannosidase, heterozygotes having one normal gene and one defective gene have approximately half the normal level of enzyme in their tissues and plasma. This observation forms the basis for a control programme in which heterozygotes are identified by their plasma α-mannosidase 1evels (Jolly et al., 1973, 1974a, b).

Extract Eperythrozoon ovis is an epi-erythrocytic sheep parasite of uncertain classification with a world-wide distribution (Sutton, 1970), but whether eperythrozoonosis is a disease of economic importance remains unresolved. In Scotland, Foggie and Nisbet (1964), found that experimentally E. ovis caused a clinical anaemia, occasionally with jaundice, but there was no significant difference in weight gain between infected and control sheep. Similar observations in naturally infected sheep were recorded in Norway by Overas (1969), and in Australia by Harbutt (1969b), Other Australian authors have found infection by this parasite; associated with outbreaks of ill-thrift in lambs (Sheriff et al., 1966) and severe anaemia with some mortality (Littlejohns, 1960; Maxwell, 1969; Campbell et al., 1971). Although the presence of strains of different pathogenicity has been suggested (Foggie and Nisbet, 1964, 1966; Harbutt, 1969a), other factors influencing the disease should also be considered (Littlejohns...

Extract The derivation of large populations of beef cattle from a smallgenetic pool has been a feature of the cattle industry in this country from the earliest days of settlement. In recent years the importation of small numbers of exotic beef cattle and the rapiddissemination of this genetic material, aided by artificial breeding techniques, has further emphasised the need to make a close study of the possible sequelae of this phenomenon in the context of genetic disease and the “founder effect”. Care should be taken not to give disproportionate emphasis to negative effects of some cattle breeding practices because these can sometimes be outweighed by the positive benefits that may accrue from the very same practices. However, it is proposed to show how, with forethought and organisation, the genetic disadvantages that have accompanied our attempts to improve beef production could have been minimised. The beef industry is a national resource and although we are reluctant to stifle entrepreneurs ...

Extract Diseases inherited as simple recessives frequently reflect simple anomalies of structural or enzymic proteins. Many such inherited diseases of humans have now been defined in biochemical terms (McKusick, 1971) but relatively few have been described adequately in domestic animals. When the biochemical anomaly is known, then it is frequently possible to develop screening programmes to detect diseased young before the disease is manifest clinically. Such programmes may involve families or small populations at risk, or be developed as mass screening programmes for the entire neonatal population of an area or country. In many biochemically defined diseases inherited as recessives, the heterozygous statecan also be recognized. This is either through detection of a mutant structural protein in the otherwise phenotypically normal individual — e.g., the “S” haemoglobin in carriers of sickle-cell anaemia (Lehmann and Huntsman, 1972) — or where an enzyme deficiency is known, by the gene dosage pheno...

Extract Caseous lymphadenitis is one of the most common specific infections of sheep in many sheep-raising countries of the world, yet comparatively little is known of its pathogenesis or the factors involved in acquired immunity, Corynebacteriwn ovis infection has been studied in guinea-pigs (Bull & Dickinson, 1931; Carne, 1934) which are highly susceptible to experimental infection and in which the disease is virtually always steadily progressive till fatal. Partly because of this extreme sensitivity to infection, this animal has not proved very satisfactory for experiments related to natural resistance or acquired immunity. With the obvious need for a more suitable experimental animal, attention was directed towards the mouse.

Extract Recently, attention has been drawn to nodular lesions in the spleens of approximately 0.75% of cast-for-age ewes at an abattoir (Webster, 1966). More than one lesion was occasionally found in a single spleen. In no case were lesions, suspected of being mestastases of a primary spleen lesion, found in other organs. These lesions were examined further with the intent of defining their nature.

Extract Mannosidosis of Angus cattle, previously known as pseudolipidosis, is an inherited lethal nervous disease (Whittem and Walker, 1957; Jolly, 1970, 1971). It has recently been shown that this condition is due to an inborn error of lysosomal catabolism of glycoproteins in which a deficiency of α-mannosidase results in storage of an oligosaccharide containing glucosamine and mannose (Hocking et al., 1972). As such it is biologically similar to other inherited lysosomal storage diseases of man and animals (Jolly and Blakemore, 1973). Whereas diseased calves have a near absolute deficiency of α-mannosidase, heterozygotes for this genotype have a partial deficiency of the enzyme. This observation could be exploited as a means of testing for heterozygous animals in the population at large. This paper augments earlier observations and describes some of the parameters that affect the level of α-mannosidase in normal individuals. The effects on enzyme activity of methods of collection and subsequent...

Extract An eaplier paper described disease caused by experimental infection of normal mice with Corynebacterium ovis (Jolly, 1965a). Local lesions developed at the site of infection while distribution of secondary lesions indicated a bacteraemic phase. Many organisms were filtered out in the liver and spleen, presumably by reticulo-endothelial cells. Organisms were able to multiply at these sites but in the spleen, and in a proportion of foci in the liver, were eventually controlled and eliminated. The earliest reaction to the organism was often histiocytic, these cells being apparently unable to kill the bacteria or inhibit their multiplication. An intense neutrophil reaction which often subsequently developed, particularly in the liver, tended to promote the development of an abscess that would have survival advantages for the organism. Lesions in the spleen and a proportion of lesions in the liver appeared to control infection about the sixth to eighth day post-infection about the sixth to eig...