Inheritance, Biochemical Abnormalities, and Clinical Features of Feline Mucolipidosis II: The First Animal Model of Human I-Cell Disease

Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage diseas

Sensor data classification for the indication of lameness in sheep

Lameness is a vital welfare issue in most sheep farming countries, including the UK. The pre-detection at the farm level could prevent the disease from becoming chronic. The development of wearable sensor technologies enables the idea of remotely monitoring the changes in animal movements which relate to lameness. In this study, 3D-acceleration, 3D-orientation, and 3D-linear acceleration sensor data were recorded at ten samples per second via the sensor attached to sheep neck collar. This research aimed to determine the best accuracy among various supervised machine learning techniques which can predict the early signs of lameness while the sheep are walking on a flat field. The most influencing predictors for lameness indication were also addressed here. The experimental results revealed that the Decision Tree classifier has the highest accuracy of 75.46%, and the orientation sensor data (angles) around the neck are the strongest predictors to differentiate among severely lame, mildly lame and sound classes of sheep

Therapeutic Neonatal Hepatic Gene Therapy in Mucopolysaccharidosis VII Dogs

Dogs with mucopolysaccharidosis VII (MPS VII) were injected intravenously at 2–3 days of age with a retroviral vector (RV) expressing canine β-glucuronidase (cGUSB). Five animals received RV alone, and two dogs received hepatocyte growth factor (HGF) before RV in an attempt to increase transduction efficiency. Transduced hepatocytes expanded clonally during normal liver growth and secreted enzyme with mannose 6-phosphate. Serum GUSB activity was stable for up to 14 months at normal levels for the RV-treated dogs, and for 17 months at 67-fold normal for the HGF/RV-treated dog. GUSB activity in other organs was 1.5–60% of normal at 6 months for two RV-treated dogs, which was likely because of uptake of enzyme from blood by the mannose 6-phosphate receptor. The body weights of untreated MPS VII dogs are 50% of normal at 6 months. MPS VII dogs cannot walk or stand after 6 months, and progressively develop eye and heart disease. RV- and HGF/RV-treated MPS VII dogs achieved 87% and 84% of normal body weight, respectively. Treated animals could run at all times of evaluation for 6–17 months because of improvements in bone and joint abnormalities, and had little or no corneal clouding and no mitral valve thickening. Despite higher GUSB expression, the clinical improvements in the HGF/RV-treated dog were similar to those in the RV-treated animals. This is the first successful application of gene therapy in preventing the clinical manifestations of a lysosomal storage disease in a large animal

West Highland White Terriers under primary veterinary care in the UK in 2016: demography, mortality and disorders

The West Highland White Terrier (WHWT) is a relatively common breed in the UK, although Kennel Club registrations have declined in recent years. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass clinical data, this study aimed to characterise the demography, longevity and common disorders of WHWTs under primary veterinary care in the UK

Sensor data classification for the indication of lameness in sheep

Lameness is a vital welfare issue in most sheep farming countries, including the UK. The pre-detection at the farm level could prevent the disease from becoming chronic. The development of wearable sensor technologies enables the idea of remotely monitoring the changes in animal movements which relate to lameness. In this study, 3D-acceleration, 3D-orientation, and 3D-linear acceleration sensor data were recorded at ten samples per second via the sensor attached to sheep neck collar. This research aimed to determine the best accuracy among various supervised machine learning techniques which can predict the early signs of lameness while the sheep are walking on a flat field. The most influencing predictors for lameness indication were also addressed here. The experimental results revealed that the Decision Tree classifier has the highest accuracy of 75.46%, and the orientation sensor data (angles) around the neck are the strongest predictors to differentiate among severely lame, mildly lame and sound classes of sheep

Skin and ear health in a group of English bulldogs in Finland - a descriptive study with special reference to owner perceptions

Background - Dermatological conditions are common in English bulldogs (EBs). Hypothesis/Objectives - This cross-sectional study describes the dermatological health status of a group of EBs and compares the results with owner perceptions and its possible impact on quality of life (QoL). Computed tomographic (CT) findings of the ear canals were compared between EBs and mesaticephalic dogs. Animals - Twenty-seven EBs participating in a health study in Finland. Methods and materials - A QoL questionnaire was completed for EBs with owner-reported clinical signs referable to the skin or ear. Clinical evaluation included recording the Canine Atopic Dermatitis Extent and Severity Index, the Otitis Index Score, false paw pad grading and the presence of interdigital furunculosis. These were summed to form a total clinical score (TCS). The cross-sectional surface areas of the horizontal ear canals were measured from CT images and compared with respective images of 14 mesaticephalic dogs collected from a patient database. Results - All 27 EBs had abnormal findings on dermatological examination, but 37% of the owners had not recognized skin or ear signs. The median QoL score was 5.0 (range 0-12) and correlated with TCS (correlation coefficient = 0.507, P <0.05). English bulldogs had narrower horizontal ear canals than mesaticephalic dogs (P <0.001). Conclusions and clinical importance - All EBs had abnormal dermatological findings that were unnoticed or considered to be of minor significance to the QoL by most owners. Narrow ear canals were common, possibly related to the brachycephalic conformation of the breed.Peer reviewe

Inheritance, Biochemical Abnormalities, and Clinical Features of Feline Mucolipidosis II: The First Animal Model of Human I-Cell Disease

Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage diseas