Sensory Ataxic Neuropathy in Golden Retriever Dogs Is Caused by a Deletion in the Mitochondrial tRNATyr Gene

Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNATyr gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0–11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNATyr had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNATyr gene is the causative mutation for SAN

Genome-Wide Association Analysis Identifies a Mutation in the Thiamine Transporter 2 (SLC19A3) Gene Associated with Alaskan Husky Encephalopathy

Alaskan Husky Encephalopathy (AHE) has been previously proposed as a mitochondrial encephalopathy based on neuropathological similarities with human Leigh Syndrome (LS). We studied 11 Alaskan Husky dogs with AHE, but found no abnormalities in respiratory chain enzyme activities in muscle and liver, or mutations in mitochondrial or nuclear genes that cause LS in people. A genome wide association study was performed using eight of the affected dogs and 20 related but unaffected control AHs using the Illumina canine HD array. SLC19A3 was identified as a positional candidate gene. This gene controls the uptake of thiamine in the CNS via expression of the thiamine transporter protein THTR2. Dogs have two copies of this gene located within the candidate interval (SLC19A3.2 – 43.36–43.38 Mb and SLC19A3.1 – 43.411–43.419 Mb) on chromosome 25. Expression analysis in a normal dog revealed that one of the paralogs, SLC19A3.1, was expressed in the brain and spinal cord while the other was not. Subsequent exon sequencing of SLC19A3.1 revealed a 4bp insertion and SNP in the second exon that is predicted to result in a functional protein truncation of 279 amino acids (c.624 insTTGC, c.625 C>A). All dogs with AHE were homozygous for this mutation, 15/41 healthy AH control dogs were heterozygous carriers while 26/41 normal healthy AH dogs were wild type. Furthermore, this mutation was not detected in another 187 dogs of different breeds. These results suggest that this mutation in SLC19A3.1, encoding a thiamine transporter protein, plays a critical role in the pathogenesis of AHE.University of California, Davis. School of Veterinary Medicine. Center for Companion Animal Healt

Age and Diet Affect Gene Expression Profile in Canine Skeletal Muscle

We evaluated gene transcription in canine skeletal muscle (biceps femoris) using microarray analysis to identify effects of age and diet on gene expression. Twelve female beagles were used (six 1-year olds and six 12-year olds) and they were fed one of two experimental diets for 12 months. One diet contained primarily plant-based protein sources (PPB), whereas the second diet contained primarily animal-based protein sources (APB). Affymetrix GeneChip Canine Genome Arrays were used to hybridize extracted RNA. Age had the greatest effect on gene transcription (262 differentially expressed genes), whereas the effect of diet was relatively small (22 differentially expressed genes). Effects of age (regardless of diet) were most notable on genes related to metabolism, cell cycle and cell development, and transcription function. All these genes were predominantly down-regulated in geriatric dogs. Age-affected genes that were differentially expressed on only one of two diets were primarily noted in the PPB diet group (144/165 genes). Again, genes related to cell cycle (22/35) and metabolism (15/19) had predominantly decreased transcription in geriatric dogs, but 6/8 genes related to muscle development had increased expression. Effects of diet on muscle gene expression were mostly noted in geriatric dogs, but no consistent patterns in transcription were observed. The insight these data provide into gene expression profiles of canine skeletal muscle as affected by age, could serve as a foundation for future research pertaining to age-related muscle diseases

Canine and feline obesity: a review of pathophysiology, epidemiology, and clinical management

John P Loftus, Joseph J Wakshlag Cornell University College of Veterinary Medicine, Veterinary Medical Center, Ithaca, NY, USAAbstract: Canine and feline obesity rates have reached pandemic proportions and are similar to those in humans, with approximately 30%–40% of dogs and cats being overweight to obese. Obesity has been associated with other health problems, including osteoarthritis, renal disease, skin disease, insulin resistance, and neoplasia in dogs, while in cats obesity is associated with dermatological issues, diabetes mellitus, neoplasia, and urolithiasis. The health issues appear to be slightly different across the two species, which may be due to some inherent differences in the hormonal milieu involved in obesity that differs between the dog and the cat. In this review, we discuss the complicated nature of the pathogenesis of obesity, the hormonal stimulus for orexigenic and anorexigenic behavior, adipose tissue as an endocrine organ, and most importantly, clinical management of the number one disease in canine and feline medicine.Keywords: obesity, canine, feline, veterinar

One-year study evaluating efficacy of an iodine-restricted diet for the treatment of moderate-to-severe hyperthyroidism in cats

John P Loftus, Sage DeRosa, Angela M Struble, John F Randolph, Joseph J Wakshlag Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA Purpose: This study sought to determine the efficacy of a therapeutic iodine-restricted diet during a 12 -month interval in cats with moderately to severely increased total thyroxine (TT4) concentrations. Patients and methods: Eight hyperthyroid cats with serum creatinine 6.0 µg/dL (reference interval 1.5–4.0 µg/dL) were enrolled. Each cat underwent an initial physical examination, complete blood count, serum chemistry panel, thyroid profile, thyroid scintigraphy, and echocardiogram. Physical examination and all blood samplings were repeated at 1, 2, 3, 6, and 12 months after enrollment. Clients were instructed to feed only the therapeutic iodine-restricted diet throughout the entire study. Results: Median TT4 was 8.4 (range 6.2–24.0) µg/dL at study onset. Thyroid scintigraphy was abnormal in all cats, confirming hyperthyroidism. Six out of eight cats had normal serum TT4 after 4 weeks of feeding the therapeutic diet. The two cats that did not achieve normalization of TT4 at 4 weeks had the highest initial TT4 concentrations. Three cats were withdrawn from the study due to emergence of chronic kidney disease. Conclusion: An iodine-restricted diet was able to control moderate-to-severe hyperthyroidism in most (six out of eight) of the cats by 4 weeks. Cats with highest baseline TT4 took substantially longer before TT4 concentrations normalized, if at all. Keywords: feline, thyroxine, free T4, nuclear scintigraphy, iodin

Evaluation of selected ultra-trace minerals in commercially available dry dog foods

Hyun-tae Kim,1 John P Loftus,1 Jason W Gagné,1 Michael A Rutzke,2 Raymond P Glahn,3 Joseph J Wakshlag1 1Cornell University College of Veterinary Medicine, Department of Clinical Sciences, Ithaca, NY, USA; 2Cornell University, College of Agriculture and Life Sciences, School of Integrative Plant Sciences, Ithaca, NY, USA; 3Robert W. Holley Center for Agriculture and Health, Agricultural Research Service, USDA, Ithaca, NY, USA Purpose: To evaluate the concentrations of chromium, nickel, molybdenum, silica, and aluminum in several commercially available dry dog foods and compare these with current World Health Organization’s (WHO) mean human daily dietary intake. Conversion of dietary intake per megacalorie (Mcal) for both dog foods and human average intake was performed based on the National Research Council recommendation of a 2,900 kcal diet for comparative purposes to average intake and potential toxic exposure.Materials and methods: Forty-nine over-the-counter dry foods formulated for maintenance of healthy dogs yet listed as all life stage foods were analyzed. Concentrations of the ultra-trace minerals were measured via inductively coupled plasma atomic emission and represented per Mcal for comparative purposes as it relates to common intake in dogs in comparison with humans.Results: Chromium, molybdenum, and aluminum concentrations in all of the dog foods were at levels that would be considered above average human daily consumption on a caloric basis. Nickel and silica calculated intakes per Mcal were comparable with human intake patterns, while both trace minerals displayed outliers exceeding at least twofold of the upper range of human daily intake.Conclusion: Overall, ultra-trace minerals found in dog foods were above the expected average daily intake for humans on a caloric basis. There was no evidence of potential chronic toxic exposure based on presumptive intake extrapolated from WHO published toxic intake concentrations for humans or domestic animals. The large range of silica intake from various foods (2.96–83.67 mg/1,000 kcal) may have health implications in dogs prone to silica urolithiasis. Further studies investigating the bioavailability of these ultra-trace minerals and establishing dietary ultra-trace mineral allowance would be ideal; however, based on these findings, consumption of these ultra-trace minerals in over-the-counter dry dog foods appears safe. Keywords: dog food, ultra-trace minerals, food safety, ICP-AE

A survey on orthopedic injuries during a marathon sled dog race

Dirsko JF von Pfeil,1,2 William D Liska,3 Stuart Nelson, Jr,4 Sabine Mann,5 Joseph J Wakshlag61Friendship Surgical Services of the Friendship Hospital for Animals, Washington, DC, 2Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 3Global Veterinary Specialists, Sugar Land, TX, 4The Iditarod Headquarters, Wasilla, AK, 5Department of Population Medicine, 6Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USAPurpose: This prospective observational study aimed to describe and quantify orthopedic injuries (OI) during a marathon sled dog race that led to discontinuation of racing (dropped dogs [DDs]) and to suggest potential associations with risk factors during the event.Study design: Prospective observational study.Animals: A total of 989 Nordic breed endurance sled dogs that participated in the 2011 Iditarod Sled Dog Race. Data were collected via an extensive questionnaire, medical records, and speed calculations based on Global Positioning System equipment on each dog sled. OI risk factors and DD incidence were statistically analyzed on dogs and teams completing at least half the race distance, including Student’s t-test, Pearson’s chi-squared test, Poisson regression, and various frailty analysis models as indicated. Significance was set at P<0.10 for inclusion in the models with trends established at P≤0.10 and significance declared at P<0.05.Results: Questionnaire response was 40.3%. DD incidence was 38.3%, most often due to OI (50.6%). OI occurred most frequently in the thoracic limb (43.3%) compared with pelvic limb injuries (7.3%). Increased speed was associated with fewer shoulder injuries (Ratio=0.65, P=0.03). Carpal injuries were positively related with increased conditioning distance (defined as training miles; Hazard ratio =1.61, P=0.02). The risk to become a DD decreased with every year of increased age of the dogs (Hazard ratio =0.92, P=0.03).Conclusion: OI, specifically of the shoulder and carpus, are common in marathon sled dogs. Injury risk may be speed-related and decreases with increasing age of the dog. Further study of environmental, dietary, and trail conditions in sled dog racing orthopedic research is needed.Keywords: veterinary sports medicine, endurance, canine, athlete, Iditarod, arcti

The associations between serum adiponectin, leptin, C-reactive protein, insulin, and serum long-chain omega-3 fatty acids in Labrador Retrievers

Renee M Streeter,1 Angela M Struble,1 Sabine Mann,2 Daryl V Nydam,2 John E Bauer,3 Marta G Castelhano,1 Rory J Todhunter,1 Bethany P Cummings,4 Joseph J Wakshlag11Department of Clinical Sciences, 2Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA; 3Department of Clinical Sciences, Texas A&M University, College Station, TX, USA; 4Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USAAbstract: Obesity has been associated with an increased inflammatory response and insulin resistance due to adipose tissue–derived adipokines and increases in C-reactive protein (CRP). Dogs appear to be similar to other species with the exception of adiponectin, which might not be affected by obesity status. Serum long-chain polyunsaturated fatty acid concentrations have been positively and negatively associated with serum adipokines. The aim of the study was to examine the relationship between leptin, CRP, adiponectin, and insulin to body condition score (BCS) and to the long-chain omega-3 fatty acids in serum lipoproteins, including alpha-linolenic acid, eicosapentaenoic acid (EPA), docosapentanenoic acid (DPA), and docosahexaenoic acid (DHA) as a reflection of dietary omega-3 status in the Labrador Retriever. Seventy-seven Labrador Retrievers were evaluated for BCS, percent fasting serum lipoprotein fatty acid concentrations, as well as serum leptin, adiponectin, insulin, and CRP. A multivariable general linear regression model was constructed to examine the association between the dependent variables leptin, CRP, adiponectin, and insulin and the predictor variables of BCS, age, and sex, as well as concentrations of alpha-linolenic acid, EPA, DHA, and DPA. Adiponectin concentration was positively associated with age (P<0.0008), EPA (P=0.027) and negatively associated with DHA (P=0.008). Leptin concentration was positively associated with an increased DHA (P=0.009), BCS (P<0.0001), age (P=0.02), and decreased DPA (P=0.06). Insulin concentration was only associated with BCS (P<0.0001), and no meaningful associations were found for CRP. Longer chain omega-3 fatty acids may play a role in regulating adiponectin concentrations in dogs. However, because insulin concentrations were associated only with BCSs, further examination of the role of adiponectin in canine obesity is warranted. EPA and DPA may reduce the overall inflammatory state in dogs as these omega-3 fatty acids reflect increased adiponectin (increased EPA and decreased DHA) and decreased leptin (decreased DHA and increased DPA).Keywords: dog, obesity, adiponectin, omega-3 fatty acid, insulin, lepti