Retinal pigment epithelial dystrophy (RPED) is a progressive retinal degeneration which occurs in a number of breeds of dog. It is characterised primarily by the accumulation of abnormal lipofuscin-like pigment granules within retinal pigment epithelial (RPE) cells of the tapetal fundus. Similar lipopigments accumulate in the RPE in man in a range of diseases and during normal ageing. It is believed that they may result from the incomplete degradation of phagocytosed photoreceptor outer segment membranes and that autoxidative processes and abnormalities in lipid metabolism may be important in their formation. The purpose of this study was to examine these hypotheses, primarily through a study of the Briard dog, a breed in which RPED is particularly prevalent. The RPE lipopigment from affected dogs was analysed and compared with similar pigments from RPE diseases in other species. Lipid and lipoprotein metabolism and plasma antioxidants were studied in normal Briard dogs and in RPED affected dogs of several breeds. The influence of a number of factors on canine RPE in vitro were investigated. Breed and species variation in RPE lipopigments were demonstrated and the pigments that accumulate in RPED were partially characterised. A primary hypercholesterolaemia was demonstrated in Briard dogs and this was further characterised by plasma lipoprotein electrophoresis and precipitation, and apolipoprotein analysis. The results of these lipoprotein and apolipoprotein studies were consistent with the findings of studies of hyperlipidaemia in human retinitis pigmentosa. Abnormalities were also demonstrated in the plasma antioxidants of RPED affected dogs. The studies of canine RPE in vitro demonstrated the effects of a number of factors on the behaviour of these cells in culture. The use of such culture techniques may represent a useful method for further investigation of the initial hypotheses in the light of the findings of this project

The canine oral microbiota is poorly understood compared to that of humans. The aim of this work was to improve understanding of the canine oral microbiota. This was achieved by surveying the canine oral microbiota, determining coaggregation interactions between its members, and developing a laboratory microcosm. Bacteria were isolated from the dental plaque and saliva of dogs, and isolates were identified by comparative 16S rRNA gene sequencing. From 339 isolates, 84 phylotypes belonging to 37 genera were identified. Approximately half were identified to species level, and 28 % of these were also members of the human oral microbiota. Thirty eight phylotypes were tentatively identified as candidate new species. The genera most frequently isolated from saliva were Actinomyces, Streptococcus, and Granulicatella. Porphyromonas, Actinomyces, and Neisseria were most frequently isolated from plaque. On average, sequences from this study differed by almost 7 % in the 16S rRNA gene compared to similar organisms from humans. Targeted PCR was used to detect culture resistant bacteria from canine plaque. Successful amplification indicated that Spirochaetes and candidate division TM7 bacteria were present, however the identities of the originating organisms were not determined. The entire cultivable plaque microbiota from a single dog was assessed for coaggregation reactions. Eight (6.7 %) unique interactions were detected from 120 crosses, indicating that the prevalence of coaggregation is similar in the canine and human oral microbiotas. Genera common to both hosts generally exhibited similar coaggregation reactions, however autoaggregation was more common among bacteria isolated from dogs. The constant depth film fermenter was used to grow microcosms from canine plaque and saliva using a mucin containing artificial saliva supplemented with horse serum as the growth medium. The model produced biofilms similar to natural dental plaque, which could be used to investigate the canine oral microbiota further.

There has been a strong public interest recently in the interrogation of canine ancestries using direct-toconsumer (DTC) genetic ancestry inference tools. Our goal is to improve the accuracy of the associated computational tools, by developing superior algorithms for identifying the breed composition of mixedbreed dogs. Genetic test data has been provided by Mars Veterinary, using SNP markers. We approach this ancestry inference problem from two main directions. The first approach is optimized for datasets composed of a small number of ancestry informative markers (AIM). Firstly, we compute haplotype frequencies from purebred ancestral panels which characterize genetic variation within breeds and are utilized to predict breed compositions. Due to a large number of possible breed combinations in admixed dogs we approximately sample this search space with a Metropolis-Hastings algorithm. As proposal density we either uniformly sample new breeds for the lineage, or we bias the Markov Chain so that breeds in the lineage are more likely to be replaced by similar breeds. The second direction we explore is dominated by HMM approaches which view genotypes as realizations of latent variable sequences corresponding to breeds. In this approach an admixed canine sample is viewed as a linear combination of segments from dogs in the ancestral panel. Results were evaluated using two different performance measures. Firstly, we looked at a generalization of binary ROC-curves to multi-class classification problems. Secondly, to more accurately judge breed contribution approximations we computed the difference between expected and predicted breed contributions. Experimental results on a synthetic, admixed test dataset using AIMs showed that the MCMC approach successfully predicts breed proportions for a variety of lineage complexities. Furthermore, due to exploration in the MCMC algorithm true breed contributions are underestimated. The HMM approach performed less well which is presumably due to using less information of the dataset.

Obesity is now one of the most common medical disorders of companion animals (dogs, cats and horses) and is defined by the expansion of white adipose tissue mass. This tissue is now known to be major endocrine and secretory organ, releasing different protein hormones and signals termed adipokines. A number of these are linked to inflammation and immunity, and a role for inflammation-related adipokines in the development of obesity-associated diseases in humans is increasingly recognised. The specific aim of this project was to examine the extent to which canine adipose tissue produces various adipokines and to determine some of the factors which regulate their production.

An investigation was carried out to determine the tissue of origin of serum alkaline phosphatase in normal dogs and in dogs treated with the insecticide dieldrin. The work involved comparisons between tissue and serum alkaline phosphatases on the basis of immunological and electrophoretic properties. Alkaline phosphatases from dog liver, kidney, intestine and bone were separable by electrophoretic pattern on polyacrylamide gel, except for some overlapping between bone and renal bands. By electrophoretic analysis, liver appeared to be the major source of serum alkaline phosphatase in both normal and hyperphosphatasemic sera from dieldrin treated dogs. Rabbit antiserum to dog intestinal alkaline phosphatase was used to demonstrate phosphatase of intestinal origin in some dog sera. The presence of this additional serum enzyme was not related to administration of dieldrin. The work was extended to an investigation of the origin of alkaline phosphatase in dog urine. Urinary phosphatase differed electrophoretically and immunologically from that of the kidney and showed some similarity to bladder alkaline phosphatase. Alkaline phosphatase from dog intestinal mucosa was shown to differ from phosphatases extractable from the predominant bacterial flora of dog duodenum and faeces. Immunofluorescence was used to demonstrate alkaline phosphatase on the outer surface of intestinal villi.

No description available.

Cranial cruciate ligament disease and rupture (CCLD/ R) is a common orthopaedic condition in dogs. CCLD/ R can be due to trauma (least common) or to non-contact injury (most common). Once the cranial cruciate ligament (CCL) is damaged complications such as stifle osteoarthritis can occur. Different dog breeds are at an altered risk to CCLD/ R. Previous biochemical and ultrastructural studies have found that glycosaminoglycans (GAGs) were altered in high risk dog breeds when compared to CCLs from a dog breed at low risk of ligament rupture. We hypothesise that proteoglycans and GAGs may vary between different anatomical regions of the CCL, and between differentially predisposed dog breeds to CCLD/ R. Proteoglycans were determined by semi-quantitative Western blotting, quantitative RT-PCR (qRT-PCR), quantitative biochemistry, semi-objective histology scoring, and immunohistochemistry. Water and GAG content in the CCLs was also measured. Further qRT-PCR analysis was conducted to determine the expression of ECM proteases (ADAMTS -4 & -5) in the canine CCL. We showed with Western blot analysis that certain proteoglycans and GAGs were significantly different between anatomical regions of Staffordshire bull terrier CCLs. Data analysis between differentially predisposed dog breeds showed that the Staffordshire bull terrier CCLs (a moderate-high risk dog breed to CCLD/ R) had a significant increase in water content compared to greyhound CCLs (a low risk dog breed to CCLD/ R). Further, gene expression and Western blot analysis of fibromodulin, gene expression of aggrecan, and Western blot analysis of chondroitin-6 sulphate stubs were significantly increased in Staffordshire bull terrier CCLs compared to greyhounds. Decorin and ADAMTS-4 gene expression were significantly increased in greyhounds compared to Staffordshire bull terrier CCLs. Histology analysis showed that fibrocartilaginous regions were present in the CCL and were mainly observed in predisposed dog breeds to CCLD/ R. Furthermore, immunohistochemistry analysis showed that each proteoglycan had a different distribution throughout the CCL, which indicates that proteoglycans provide essential functionality to the CCL. The increase of certain proteoglycans and GAGs in CCLs of Staffordshire bull terriers might indicate increased fibrocartilage regions as a result of compressive loads. These changes in ECM content in the Staffordshire bull terrier indicate higher loading pressure on the CCL and could compromise the tissue, leading to increased incidence of disease and rupture. The increase of decorin in greyhounds could be essential for maintaining collagen fibril strength, whilst the increase of ADAMTS-4 could indicate a higher rate of turnover to regulate normal CCL homeostasis.

No description available.

No description available.

No description available.