Kinematic analysis of Labrador Retrievers and Rottweilers trotting on a treadmill

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A mutation in the SUV39H2 gene in Labrador Retrievers with hereditary nasal parakeratosis (HNPK) provides insights into the epigenetics of keratinocyte differentiation.

Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4×10⁻¹⁴). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38× coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.

A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

Two Loci on Chromosome 5 Are Associated with Serum IgE Levels in Labrador Retrievers

Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.

Correlation of urinary nitric oxide concentrations with the development of hip dysplasia in Labrador retrievers

Urinary nitric oxide was determined in terms of the ratio of the concentrations of total urinary nitrite and nitrate:creatinine in 40 juvenile labrador retrievers, and radiographic signs of hip dysplasia and distraction indices were investigated in the same dogs in later life. The ratio was correlated significantly with the Norberg angle and with subchondral sclerosis in both hips, and with the grade of dysplasia in each hip and the dogs' overall grade of hip dysplasia. No correlations were observed between the ratio and the distraction indices or other radiographic criteria for hip dysplasia.

Gait analysis of the hind limb in Labrador Retrievers with and without cranial cruciate ligament disease

Cranial cruciate ligament (CCL) deficiency is the leading cause of lameness affecting the stifle joints of large breed dogs, especially Labrador Retrievers. Although CCL disease has been studied extensively, its exact pathogenesis and the primary cause leading to CCL rupture remain controversial. However, weakening secondary to repetitive microtrauma is currently believed to cause the majority of CCL instabilities diagnosed in dogs. Techniques of gait analysis have become the most productive tools to investigate normal and pathological gait in human and veterinary subjects. The inverse dynamics analysis approach models the limb as a series of connected linkages and integrates morphometric data to yield information about the net joint moment, patterns of muscle power and joint reaction forces. The results of these studies have greatly advanced our understanding of the pathogenesis of joint diseases in humans. A muscular imbalance between the hamstring and quadriceps muscles has been suggested as a cause for anterior cruciate ligament rupture in female athletes. Based on these findings, neuromuscular training programs leading to a relative risk reduction of up to 80% has been designed. In spite of the cost and morbidity associated with CCL disease and its management, very few studies have focused on the inverse dynamics gait analysis of this condition in dogs. The general goals of this research were (1) to further define gait mechanism in Labrador Retrievers with and without CCL-deficiency, (2) to identify individual dogs that are susceptible to CCL disease, and (3) to characterize their gait. The mass, location of the center of mass (COM), and mass moment of inertia of hind limb segments were calculated using a noninvasive method based on computerized tomography of normal and CCL-deficient Labrador Retrievers. Regression models were developed to determine predictive equations to estimate body segment parameters on the basis of simple morphometric measurements, providing a basis for nonterminal studies of inverse dynamics of the hind limbs in Labrador Retrievers. Kinematic, ground reaction forces (GRF) and morphometric data were combined in an inverse dynamics approach to compute hock, stifle and hip net moments, powers and joint reaction forces (JRF) while trotting in normal, CCL-deficient or sound contralateral limbs. Reductions in joint moment, power, and loads observed in CCL-deficient limbs were interpreted as modifications adopted to reduce or avoid painful mobilization of the injured stifle joint. Lameness resulting from CCL disease affected predominantly reaction forces during the braking phase and the extension during push-off. Kinetics also identified a greater joint moment and power of the contralateral limbs compared with normal, particularly of the stifle extensor muscles group, which may correlate with the lameness observed, but also with the predisposition of contralateral limbs to CCL deficiency in dogs. For the first time, surface EMG patterns of major hind limb muscles during trotting gait of healthy Labrador Retrievers were characterized and compared with kinetic and kinematic data of the stifle joint. The use of surface EMG highlighted the co-contraction patterns of the muscles around the stifle joint, which were documented during transition periods between flexion and extension of the joint, but also during the flexion observed in the weight bearing phase. Identification of possible differences in EMG activation characteristics between healthy patients and dogs with or predisposed to orthopedic and neurological disease may help understanding the neuromuscular abnormality and gait mechanics of such disorders in the future. Conformation parameters, obtained from femoral and tibial radiographs, hind limb CT images, and dual-energy X-ray absorptiometry, of hind limbs predisposed to CCL deficiency were compared with the conformation parameters from hind limbs at low risk. A combination of tibial plateau angle and femoral anteversion angle measured on radiographs was determined optimal for discriminating predisposed and non-predisposed limbs for CCL disease in Labrador Retrievers using a receiver operating characteristic curve analysis method. In the future, the tibial plateau angle (TPA) and femoral anteversion angle (FAA) may be used to screen dogs suspected of being susceptible to CCL disease. Last, kinematics and kinetics across the hock, stifle and hip joints in Labrador Retrievers presumed to be at low risk based on their radiographic TPA and FAA were compared to gait data from dogs presumed to be predisposed to CCL disease for overground and treadmill trotting gait. For overground trials, extensor moment at the hock and energy generated around the hock and stifle joints were increased in predisposed limbs compared to non predisposed limbs. For treadmill trials, dogs qualified as predisposed to CCL disease held their stifle at a greater degree of flexion, extended their hock less, and generated more energy around the stifle joints while trotting on a treadmill compared with dogs at low risk. This characterization of the gait mechanics of Labrador Retrievers at low risk or predisposed to CCL disease may help developing and monitoring preventive exercise programs to decrease gastrocnemius dominance and strengthened the hamstring muscle group.

Total IgE and allergen-specific IgE and IgG antibody levels in sera of atopic dermatitis affected and non-affected Labrador- and Golden retrievers.

Canine atopic dermatitis (CAD) is an allergic skin disease associated with IgE and IgG antibodies (Ab) to environmental allergens. The aim of this study was to determine which other factors influence serum Ab levels in CAD-affected and non-affected dogs as this has only been poorly investigated in dogs so far. Total and allergen-specific IgE levels and Dermatophagoides farinae (DF)-specific IgG1 and IgG4 were measured by ELISA in sera of 145 CAD-affected and 271 non-affected Labrador- and Golden retrievers. A multivariable logistic regression analysis including the factors age, breed, gender, castration, clinical CAD status and allergen-specific immunotherapy (ASIT) was performed. Golden retrievers had more frequently total (OR=1.87, 95% CI=1.26-2.87, p<0.01) and specific IgE levels above the threshold value than Labrador retrievers, suggesting that genetic factors influence IgE levels in dogs. Castration was generally associated with low Ab levels (OR=0.43-0.65, p<0.05). Surprisingly, dogs with CAD did not have increased odds for high IgE against any of the allergens tested. ASIT with DF was associated with high DF-specific IgG1 (OR=4.32, 95% CI 1.46-12.8, p<0.01) but was not associated with DF-specific IgG4 or decreased IgE levels. Further studies are needed to understand the role of allergen-specific IgE in CAD and of IgG1 in ASIT.

Tibial plato leveling osteotomy

The tibial plateau leveling osteotomy (TPLO) is a relatively new and innovative surgical treatment for the cranial cruciate ligament rupture in the canine species. The real intent of the procedure is to provide functional stability to the stifle joint by eliminating or neutralizing the cranial tibial thrust during weight bearing instead to restore the cranial cruciate ligament function. The proposal of this study is to report a review of the TPLO procedure, emphasizing procedure, surgical technique, post operative care and complications. The TPLO procedure consists in a radial osteotomy in the tibial plato and rotation of the caudal plateau in order to obtain a desired angle, After the leveling of the tibial plateau, a bone plate and screws are used to stabilize the osteotomy until bone is healed up. The complications that have been associated with the procedure include tibial tuberosity fracture and patellar tendon tendinosis. This procedure has become increasingly more popular for surgical treatment of cranial cruciate ligament injuries in large breed dog. The long term clinical results have not been completely elucidated yet. It has been showed that this technique doesn`t halt the degenerative joint disease.

Esplenopatias cirúrgicas em cães, estudo retrospetivo num hospital de referência na área da Grande Lisboa

As esplenopatias são doenças comuns em canídeos que tanto podem estar associadas com doenças benignas com excelente prognóstico, como doenças com alto grau de malignidade com elevada taxa de mortalidade. O objetivo do presente trabalho foi caracterizar a população de canídeos esplenectomizados num hospital de referência na área da grande Lisboa. A população foi constituída por 73 indivíduos da espécie Canis familiaris sujeitos a esplenectomia total ou parcial. A população foi analisada e distribuída segundo vários parâmetros, como o a raça, o sexo, a idade, o diagnóstico pré-cirúrgico, o diagnóstico histopatológico, o hematócrito pré cirúrgico e por fim a sobrevida. Da análise total de canídeos, observou-se que, a maioria dos canídeos esplenectomizados eram do género masculino, de raça indeterminada e com uma média de 10 anos de idade. Constatou-se que cerca de metade dos canídeos esplenectomizados sobreviveram após um ano da cirurgia e que o diagnóstico histopatológico mais comum foi o hemangiossarcoma, seguido do hematoma esplénico. Através dos testes estatísticos conclui-se que o hematócrito não apresenta qualquer relação com a sobrevida dos animais, embora possa estar relacionado com o diagnóstico histopatológico. Este estudo visou ainda uma caracterização detalhada dos canídeos diagnosticados com hemangiossarcoma. Os animais mais afectados nesta amostra, eram do género masculino com 9anos de idade e eram da raça Boxer e Labrador. Confirmou-se ainda que esta é uma doença com mau prognóstico, apresentando uma taxa de mortalidade de 80%.

Muscular Dystrophy in Dogs: Does the Crossing of Breeds Influence Disease Phenotype?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação fisiológica e comportamental de cães utilizados em terapia assistida por animais (TAA)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Clinical and Breed Characteristics of Idiopathic Head Tremor Syndrome in 291 Dogs: A Retrospective Study.

Objective. To establish signalment and phenomenology of canine idiopathic head tremor syndrome (IHTS), an episodic head movement disorder of undetermined pathogenesis. Design. Retrospective case series. Animals. 291 dogs with IHTS diagnosed between 1999 and 2013. Procedures. Clinical information was obtained from an online community of veterinary information aggregation and exchange (Veterinary Information Network, 777 W Covell Boulevard, Davis, CA 95616) and conducted with their approval. Information on breed, sex, age of onset, tremor description, mentation during the event, effect of distractions and drugs, diagnostics, presence of other problems, and outcome was analyzed. Results. IHTS was found in 24 pure breeds. Bulldogs, Labrador Retrievers, Boxers, and Doberman Pinschers comprised 69%; mixed breeds comprised 17%. Average onset age was 29 months (range: 3 months to 12 years). First episode occurred before 48 months of age in 88%. Vertical (35%), horizontal (50%), and rotational (15%) movements were documented. Possible trigger events were found in 21%. Mentation was normal in 93%. Distractions abated the tremor in 87%. Most dogs did not respond to antiepileptic drugs. Conclusions and Clinical Relevance. This retrospective study documents IHTS in many breeds including Labrador Retrievers, Boxers, and mixed breeds.

Role of the environment in the development of canine atopic dermatitis in Labrador and golden retrievers

Canine and human atopic dermatitis are multifaceted diseases whose clinical development may be influenced by several factors, such as genetic background, environment, secondary infections, food and psychological effects. The role of the environment has been extensively examined in humans but remains unclear in dogs. The aim of this study was to examine environmental factors in two genetically close breeds, Labrador and golden retrievers. Using standard criteria, atopic dogs in Switzerland and Germany were selected and compared with healthy individuals. Information on environmental factors was collected using a 46-question survey encompassing date and place of birth, way of life at the breeder's and owner's home, food and treatments. Univariate and multivariate logistic regression were used to assess the association between potential risk factors and disease status. The following parameters were associated with an increased risk of disease development: living in a shed during puppyhood, adoption at the age of 8-12 weeks and washing the dog regularly. In contrast, the following factors were associated with a lower risk: living in a rural environment, living in a household with other animals and walking in a forest. These associations do not prove causality but support the primary hypothesis that certain environmental factors may influence the development of canine atopic dermatitis. Further studies are warranted to confirm these results and conclusions.

Explorations in the interior of the Labrador peninsula, the country of the Montagnais and Nasquapee Indians. By Henry Youle Hind...

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Anthropometric observations on the Eskimos and Indians of Labrador / by T. Dale Stewart --. Material and data collected by William Duncan Strong --. Chicago, 1939.

v.31:no.1(1939)