Hereditary myopathy in Labrador retrievers: a morphologic study

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.     

Isoelectric focusing under dissociating conditions for analysis of muscle protein from clinically normal dogs and Labrador retrievers with hereditary myopathy

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.     

Azoospermia in two Labrador retrievers

Azoospermia is described in two sibling Labrador Retriever dogs. Clinical investigations following failure to sire pups after normal matings revealed testicular hypoplasia and degeneration. Sperm were absent on repeated ejaculate examination in both dogs. Histopathological examination of testicular needle aspirate biopsy and whole testicle of the first dog displayed an absence of spermatids and spermatocytes. Seminiferous tubules containing Sertoli cells with or without primary spermatogonia were present in the second dog. Peritubular lymphocyte accumulation was also present in both dogs. The dogs had been conceived using frozen-thawed semen.     

Genetic aspects of idiopathic epilepsy in Labrador retrievers

A study was undertaken to define the mode of inheritance of idiopathic epilepsy in Labrador retrievers in Switzerland. Seven hundred and ninety-two pedigree certificates from a population of healthy and epileptic dogs from 11 generations were evaluated. Forty-four different families (giving a total of 55 epileptic dogs) were included. Most patients showed generalised grand mal seizures and the onset was within one to three years in 41 per cent. Males were no more affected than females and the gender ratio between epileptic and control animals was not significantly different (P>0·05). Additionally, there was no difference in average total inbreeding coefficient between both sexes, or with respect to age of onset of seizures. The increased manifestation of seizures in some subpopulations and the repeated occurrence in different families of the same sires suggested that there was a genetic basis for the condition in the breed. Results of pedigree analyses and from use of the binomial test support the hypothesis of a polygenic, recessive mode of inheritance. However, only an objective test-mating programme is likely to define the exact mode of inheritance.     

Canine hip and elbow dysplasia in UK Labrador retrievers

This paper examines the outcomes from recent genetic analyses of hip and elbow scores from British Veterinary Association (BVA)/UK Kennel Club (KC) screening programmes targeted at reducing the prevalence of hip dysplasia (HD) and elbow dysplasia in UK Labrador retrievers. The analyses made use of 25,243 hip scores and 3613 elbow scores. Heritabilities (± standard error) for hip score, analysed on a log scale, and for elbow score were 0.35±0.02 and 0.19±0.04, respectively, with a genetic correlation of 0.41±0.09. For both hip and elbow scores, there was a near perfect genetic correlation between the left and right joint; analysis of hip score showed a predictive benefit of using the total of left and right scores rather than worst score and the benefit of using all component scores rather than their aggregate score. Downward genetic trends were observed in both hip and elbow scores, although the latter was consistent with it being correlated to response to genetic change in hip score. Estimated breeding values (EBVs) offered substantial benefits in accuracy and hence genetic progress when compared to the use of phenotypes for both hip and elbow scores. There are major opportunities for improving selection against elbow dysplasia through the use of bivariate evaluations, although progress against dysplasia would be improved by more widespread elbow scoring. The studies highlighted a number of ways in which data recording for addressing complex traits may be improved in the future. Ongoing advances in genomic technology may be utilised for increasing the rate of genetic progress in selection against HD and for complex diseases in general, through the use of genomic evaluations.     

Incomplete ossification of the humeral condyle in two Labrador retrievers

Incomplete ossification of the humeral condyle (IOHC) was identified in two Labrador retrievers using computed tomography. Both dogs were non-weightbearing on the affected forelimbs. The dogs were treated by means of a bone screw placed across the humeral condyle. IOHC was originally reported in spaniel and chondrodystrophic breeds. The pathogenesis of the condition remains unknown, but may be related to impaired antebrachial bone growth, similarly to the pathogeneses of elbow dysplasia and radius curvus.     

Phenotyping of lumbosacral stenosis in Labrador retrievers using computed tomography

Deep phenotyping tools for characterizing preclinical morphological conditions are important for supporting genetic research studies. Objectives of this retrospective, cross‐sectional, methods comparison study were to describe and compare qualitative and quantitative deep phenotypic characteristics of lumbosacral stenosis in Labrador retrievers using computed tomography (CT). Lumbosacral CT scans and medical records were retrieved from data archives at three veterinary hospitals. Using previously published qualitative CT diagnostic criteria, a board‐certified veterinary radiologist assigned dogs as either lumbosacral stenosis positive or lumbosacral stenosis negative at six vertebral locations. A second observer independently measured vertebral canal area, vertebral fat area, and vertebral body area; and calculated ratios of vertebral canal area/vertebral body area and vertebral fat area/vertebral body area (fat area ratio) at all six locations. Twenty‐five dogs were sampled (lumbosacral stenosis negative, 11 dogs; lumbosacral stenosis positive, 14 dogs). Of the six locations, cranial L6 was the most affected by lumbosacral stenosis (33%). Five of six dogs (83%) with clinical signs of lumbosacral pain were lumbosacral stenosis positive at two or more levels. All four quantitative variables were significantly smaller at the cranial aspects of the L6 and L7 vertebral foramina than at the caudal aspects (P < 0.0001). Fat area ratio was a significant predictor of lumbosacral stenosis positive status at all six locations with cranial L6 having the greatest predictive value (R² = 0.43) and range of predictive probability (25–90%). Findings from the current study supported the use of CT as a deep phenotyping tool for future research studies of lumbosacral stenosis in Labrador retrievers.     

Digital analysis of ulnar trochlear notch sclerosis in Labrador retrievers

OBJECTIVES: To compare ulnar trochlear notch bone radiopacity in Labrador retrievers with and without fragmented medial coronoid process using quantitative analysis of film density on digitised radiographs. METHODS: Mediolateral view elbow radiographs from Labrador retrievers (n=34) aged between six and 18 months were obtained and digitised. Images from dogs with an arthroscopic diagnosis of fragmentation of the medial coronoid process (n=17) were compared with that of a control population (n=17), and this data subject to statistical analysis. RESULTS: A statistically significant relationship between the presence of increased trochlear notch radiopacity and a fragmented medial coronoid process was identified. Fractional analysis of this area shows the region of greatest difference in radiopacity between normal and fragmented medial coronoid process cohorts to be in the trochlear region of the medial coronoid process of the ulna. A decrease in radiopacity values in the dysplastic group versus the normal cohort was observed for the region of the proximo-caudal ulnar trochlear notch. CLINICAL SIGNIFICANCE: An increase in ulnar trochlear notch radiopacity is a finding associated with fragmentation of the medial coronoid process in Labrador retrievers.     

Inheritance of associated ocular and skeletal dysplasia in Labrador retrievers

A breeding colony was established to investigate the inheritance of associated ocular and skeletal dysplasia in Labrador Retrievers; 124 pups were produced. These pups were evaluated for the presence of ocular lesions, including cataracts, vitreous strands, persistent hyaloid remnants, retinal folds, retinal dysplasia, peripapillary hyperreflectivity, and rhegmatogenous retinal detachments, and skeletal abnormality, which was recognized by shorter than normal forelimbs and an abnormal morphologic appearance of the radius and ulna. Analysis of the distribution of lesions in pups indicated that the syndrome is caused by one abnormal gene, which has recessive effects on the skeleton and incompletely dominant effects on the eye. This would suggest that suspect carrier dogs could be identified by test matings with a known homozygote.     

Genotyping of exercise-induced collapse in Labrador retrievers using an allele-specific PCR

Exercise-induced collapse (EIC) is an autosomal recessive disorder in Labrador retrievers. In this study, an allele-specific PCR was developed to detect the point mutation G767T in exon 6 of canine DNM1, previously shown to be responsible for canine EIC. Of 133 Labrador retrievers tested in Japan, 6 (4.5%) were homozygous (EIC) and 50 (37.6%) were heterozygous (carriers) for the G767T mutation.     

A longitudinal assessment of periodontal health status in 53 Labrador retrievers

Objectives

To determine the incidence and rates of progression of gingivitis and periodontitis in Labrador retrievers.

Materials and Methods

Fifty‐three dogs, aged 1·1 to 5·9 years, had their periodontal health assessed every 6 months for up to 2 years. The extent of gingivitis and periodontitis was measured around the whole gingival margin of every tooth under general anaesthesia.

Results

All dogs had gingivitis at the initial assessment. The majority (64·2%) of tooth aspects had very mild gingivitis. The palatal/lingual aspect of all tooth types was most likely to show bleeding when probed: 63·0% of these aspects had mild or moderate gingivitis. Over 2 years, 56·6% of dogs developed periodontitis and dogs as young as 1·9 years were affected. There was a significant positive correlation between the proportion of teeth with periodontitis and age. In total, 124 teeth (5·7%) developed periodontitis; 88 (71·0%) of these were incisors. The palatal/lingual aspect of the incisors developed the disease first (2·8% of incisor aspects).

Clinical Significance

Periodontitis developed in regions that are difficult to see in conscious dogs implying that detection and treatment of disease requires periodic sedation or anaesthesia.     

A two-dimensional analysis of limb symmetry in the trot of Labrador retrievers

Sixteen sound Labrador retriever and Labrador retriever cross-breed adult dogs were evaluated for symmetry while in a trot gait using a two-dimensional motion analysis system. Reflective markers were placed at selected joint centers. Each dog had the right side and then the left side videotaped while in the trot gait. The markers on the videotape were then digitized for analysis. There was no significant difference (p less than 0.05) between the movements of the two sides. It was concluded that the trot gait is symmetrical and that a two-dimensional system can be used to analyze gait in the dog.     

Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers

The effects of dirlotapide on body weight (BW) reduction were investigated in overweight Labradors in two parallel-design studies. Study A involved 42 dogs randomized to 0.0, 0.025, 0.05, 0.1, 0.2 or 0.4 mg dirlotapide/kg/day orally for 4 weeks. Study B involved 72 dogs randomized to nine treatments: placebo (24 weeks); dirlotapide (24 weeks) followed by placebo (28 weeks); or dirlotapide (52 weeks); on diets containing 5%, 10% or 15% fat. Dirlotapide dose (initially 0.1 mg/kg) was adjusted monthly during 24-week weight-loss and subsequent 28-week weight-stabilization phases. Food was offered above maintenance energy requirements (MER× 1.1–1.2) based on initial BW. Body composition (body fat, lean tissue and bone mineral content) was monitored using dual-energy X-ray absorptiometry. After treatment, dogs that had received dirlotapide for 52 weeks were fed 90% of quantity consumed at week 52. In study A, BW and food intake decreased asymptotically with dose: mean weekly weight loss exceeded 1% at 0.1–0.4 mg/kg. In study B, dirlotapide resulted in significant mean weekly weight loss (>0.8%) and decreased food intake over 24 weeks compared with placebo ( P  = 0.0001) for all diets. Food restriction minimized post-treatment weight rebound. Dirlotapide administered daily to dogs for up to 52 weeks was clinically safe and resulted in sustained weight reduction.     

Genetic aspects of Labrador Retriever myopathy

Labrador Retriever myopathy (LRM) has become a relatively common muscular disease. The objective of our prospective study was to determine by segregation analyses a plausible mode of inheritance within a Labrador Retriever population. Therefore we performed neurological examinations, as well as electromyographic and histopathological evaluations of 58 closely related dogs. Seven dogs with an average age of 27.8 months had clinical signs consistent with LRM including exercise intolerance or fatigue. The diagnosis was based on neurological deficits and confirmed by histopathological results of muscle biopsy. We found in all cases obvious differences in fiber calibre size associated with texture disturbances. In addition, we found 41 clinically normal dogs with histological findings consistent with LRM. Three genetic models, the major gene, the mixed inheritance as well as the environmental model, were evaluated by segregation analyses. They were applied to an extended pedigree including 164 non-randomly ascertained related Labradors. According to phenotype the clinically examined dogs were divided into two different data sets. One data set distinguished between clinically normal and abnormal dogs, the second data set between histopathologically normal and abnormal dogs. We concluded that the clinical form of LRM is transmitted by a major gene and controlled by an autosomal recessive mode of inheritance. Furthermore, for expression of the subclinical form an additional gene or an environmental factor is responsible. Our findings suggest that LRM is similar to limb-girdle muscular dystrophy in man and therefore, may be used in the future as an animal model.     

Telemetric measurement of body core temperature in exercising unconditioned Labrador retrievers

This project evaluated the use of an ingestible temperature sensor to measure body core temperature (Tc) in exercising dogs. Twenty-five healthy, unconditioned Labrador retrievers participated in an outdoor 3.5-km run, completed in 20 min on a level, 400-m grass track. Core temperature was measured continuously with a telemetric monitoring system before, during, and after the run. Data were successfully collected with no missing data points during the exercise. Core temperature elevated in the dogs from 38.7 ± 0.3°C at pre-exercise to 40.4 ± 0.6°C post-exercise. While rectal temperatures are still the standard of measurement, telemetric core temperature monitors may offer an easier and more comfortable means of sampling core temperature with minimal human and mechanical interference with the exercising dog.     

Analysis of muscle elements, water, and total lipids from healthy dogs and Labrador retrievers with hereditary muscular dystrophy

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.     

Canine leishmaniasis caused by Leishmania leishmania infantum in two Labrador retrievers.

Canine leishmaniasis, a generally fatal parasitic disease, was diagnosed in 2 dogs with a medical history of foreign travel, lymphadenopathy, emaciation, anorexia, intermittent fever, and cutaneous lesions. Clinically, hyperproteinemia, proteinuria, azotemia, and glomerulopathy were evident. Isolation of Leishmania species was done using Schneider's Drosophila medium. Syrian hamsters were used for infectivity studies. Clear taxonomic identification was done biochemically by isoenzyme analysis and comparison of zymogram banding patterns with 6 World Health Organization reference strains. Based on the geographic origin of affected dogs, clinicopathologic presentation, visceralization with hepatosplenomegaly in hamsters, and isoenzyme analysis, a diagnosis of Leishmania leishmania infantum was made. This study, representing the first taxonomic identification of an isolate from canine leishmaniasis, demonstrates the zoonotic and epidemiologic implications of this disease.