Mutations in the MTM1 gene encoding myotubularin cause X-linked myotubular myopathy (XLMTM), a well-defined subtype of human centronuclear myopathy. Seven male Labrador Retrievers, age 14-26 wk, were clinically evaluated for generalized weakness and muscle atrophy. Muscle biopsies showed variability in fiber size, centrally placed nuclei resembling fetal myotubes, and subsarcolemmal ringed and central dense areas highlighted with mitochondrial specific reactions. Ultrastructural studies confirmed the centrally located nuclei, abnormal perinuclear structure, and mitochondrial accumulations. Wild-type triads were infrequent, with most exhibiting an abnormal orientation of T tubules. MTM1 gene sequencing revealed a unique exon 7 variant in all seven affected males, causing a nonconservative missense change, p.N155K, which haplotype data suggest derives from a recent founder in the local population. Analysis of a worldwide panel of 237 unaffected Labrador Retrievers and 59 additional control dogs from 25 other breeds failed to identify this variant, supporting it as the pathogenic mutation. Myotubularin protein levels and localization were abnormal in muscles from affected dogs, and expression of GFP-MTM1 p.N155K in COS-1 cells showed that the mutant protein was sequestered in proteasomes, where it was presumably misfolded and prematurely degraded. These data demonstrate that XLMTM in Labrador Retrievers is a faithful genetic model of the human condition.congenital myopathy | myotubularin | necklace fibers | canine myopathy | animal model X -linked myotubular myopathy (XLMTM) is a well-defined subgroup of the centronuclear myopathies (CNMs) characterized by early onset and the presence of uniformly small muscle fibers with centrally placed nuclei resembling fetal myotubes (1, 2). Although centrally located nuclei can be found in many myopathies, clinical, genetic, and pathological factors can help distinguish these myopathies from XLMTM. Onset of clinical signs is typically at or near birth, and affected males have profound hypotonia and weakness accompanied by respiratory difficulties that usually require ventilatory support. The defective gene, MTM1, was identified in 1996 by positional cloning (3). Myotubularin, the protein encoded by the MTM1 gene, is a ubiquitously expressed phosphoinositide phosphatase implicated in intracellular vesicle trafficking and autophagy (4, 5). In skeletal muscle, myotubularin localizes to the triadic regions, where it likely plays a role in lipid biogenesis or metabolism (6).Animal models have played an important role in understanding the pathogenesis of how loss of MTM1 function leads to clinically evident myotubular myopathy. A classical knockout (KO) for the murine Mtm1 gene showed that myotubularin-deficient mice developed a progressive CNM during postnatal life that severely reduced life expectancy (7). Studies in this model, as well as in a related muscle-specific KO line, have demonstrated that myotubularin plays a role in muscle maintenance rather than maturation, and have c...

Dogs with a lactate concentration higher than the reference interval at 6 hours were more likely not to survive. These results indicate an association between lactate concentration and outcome and emphasize the importance of serial lactate concentrations in evaluating prognosis.

Although precision was good with fixed sample volumes, blood lactate concentrations obtained on the Accutrend were significantly different than those on the Rapidlab 865, with systematic and random errors resulting in a positive bias. Further evaluation of the Accutrend is required before its use in dogs can be recommended.

BackgroundThe clinicopathologic aspects of pyelonephritis have not been reported in companion animals.Hypothesis/ObjectivesTo evaluate the prevalence of pyelonephritis diagnosed in dogs in a academic referral population, describe the clinical signs and the diagnostic test results in dogs with pyelonephritis, and identify concurrent disorders in order to determine potential risk factors for pyelonephritis.AnimalsForty‐seven dogs with a histopathologic diagnosis of pyelonephritis from the teaching hospitals of three Canadian veterinary colleges.MethodsRetrospective case series. Review of medical records and renal histologic sections.ResultsPyelonephritis was diagnosed in 0.4–1.3% of the cases at necropsy. Clinical signs included anorexia or inappetence (n = 27, 57%), lethargy (n = 24, 51%), vomiting (n = 17, 36%), and dehydration (n = 12, 25%). Thirty‐five dogs (75%) had concomitant disease(s). Escherichia coli was the most common pathogen isolated (37%). Pyelonephritis was classified as acute (n = 12, 26%), subacute (n = 9, 19%), and chronic (n = 26, 55%) disease; and mild (n = 7, 15%), moderate (n = 11, 24%), and severe (n = 28, 61%). Fever was significantly associated with histopathologically subacute pyelonephritis (P = 0.01).ConclusionsIn referral hospitals, pyelonephritis has a very low prevalence at necropsy. Nonspecific clinical presentation, concomitant diseases, and high variability in the diagnostic tests results make the antemortem diagnosis of pyelonephritis challenging. Neither the histopathologic stage nor the severity of the pyelonephritis was associated with fever, lumbar pain, or signs of a urinary tract infection (ie, lower urinary tract infection, upper urinary tract infection, or both) except for subacute pyelonephritis which was associated with fever.

BackgroundSeven male Labrador Retriever puppies from 3 different litters, born to clinically normal dams and sires, were evaluated for progressive weakness and muscle atrophy. Muscle biopsies identified a congenital myopathy with pathologic features consistent with myotubular myopathy. Further investigations identified a pathogenic mutation in the myotubularin gene, confirming that these puppies had X‐linked myotubular myopathy (XLMTM).ObjectiveTo review the clinical phenotype, electrodiagnostic and laboratory features of XLMTM in this cohort of Labrador Retrievers.ResultsMale puppies with XLMTM were small and thin compared with their normal littermates. Generalized weakness and muscle atrophy were present by 7 weeks of age in some puppies and evident to most owners by 14 weeks of age. Affected puppies stood with an arched spine and low head carriage, and walked with a short, choppy stride. Muscle atrophy was severe and progressive. Patellar reflexes were absent. Laryngeal and esophageal dysfunction, and weakness of the masticatory muscles occurred in puppies surviving beyond 4 months of age. Serum creatine kinase activity was normal or only mildly increased. EMG findings were nonspecific and included positive sharp waves and fibrillation potentials. Clinical signs progressed rapidly, with most affected puppies unable to walk within 3–4 weeks after clinical signs were first noticed.Conclusions and Clinical ImportanceAlthough initial clinical signs of XLMTM are similar to the phenotypically milder centronuclear myopathy in Labrador Retrievers, XLMTM is a rapidly progressive and fatal myopathy. Clinicians should be aware of these 2 distinct myopathies with similar clinical presentations in the Labrador retriever breed.

Abstract. The objective of the present study was to measure serum C-reactive protein (CRP) concentrations in 32 dogs with acute abdomen syndrome at presentation and after 48-72 hr. Data were evaluated to determine if there was an association between CRP concentration and outcome, and if CRP concentration correlated with the white blood cell (WBC) count at both time points. An immunoturbidimetric assay for human CRP, previously validated for use in dogs, was used for serum CRP analysis. Increased serum CRP concentrations were found in 21 dogs at presentation. Fifteen of these dogs had declining serum CRP concentrations by 48-72 hr, but 3 of the 15 dogs were later euthanized. Serum CRP concentrations increased by 48-72 hr in 4 dogs. Of the 32 dogs, 4 were dead or were euthanized prior to the 48-72 hr time point. No significant difference between initial CRP concentration and outcome was found (P 5 0.054). Initial and 48-72 hr CRP values taken together were significantly different between outcome groups (P , 0.001). Serum CRP concentrations that were elevated at both time points were associated with a poor prognosis. No correlation was found between CRP concentrations and WBC counts at presentation (P 5 0.83); however, a significant correlation was noted at 48-72 hr (P 5 0.03). Evaluation of sequential CRP concentrations in dogs with acute abdomen syndrome may be helpful in assessing clinical response to treatment and predicting outcome. Also, serum CRP may be better in detecting tissue injury and/or inflammation at presentation than WBC counts in select cases.

BackgroundDyslipidemia, dysregulated adipokine secretion and alteration in glucagon and adropin concentrations are important obesity-related factors in the pathophysiology of human Type 2 diabetes; however, their roles in the pathophysiology of feline diabetes mellitus are relatively unknown. Here, we determined the concentrations of circulating leptin, adiponectin, pro-inflammatory cytokines, glucagon, adropin, triglycerides, and cholesterol, in non-diabetic lean and overweight cats and newly diagnosed diabetic cats. Client-owned cats were recruited and assigned into 3 study groups: lean, overweight and diabetic. Fasting blood samples were analyzed in lean, overweight and diabetic cats at baseline and 4 weeks after consumption of high protein/low carbohydrate standardized diet.ResultsSerum concentrations of triglycerides were greater in diabetics at baseline and were increased in both diabetic and overweight cats at 4 weeks. Plasma leptin concentrations were greater in diabetic and overweight at baseline and 4 weeks, whereas adiponectin was lower in diabetics compared to lean and overweight cats at baseline and 4 weeks. Diabetics had greater baseline plasma glucagon concentrations compared to lean, lower adropin than overweight at 4 weeks, and lower IL-12 concentrations at 4 weeks than baseline.ConclusionsOur results suggest that feline obesity and diabetes mellitus are characterized by hypertriglyceridemia and hyperleptinemia; however, diabetic cats have significantly lower adiponectin and adropin compared to overweight cats. Thus, despite having similar body condition, overweight and diabetic cats have differential circulating concentrations of adiponectin and adropin.

Primary renal lymphosarcoma in dogs has rarely been reported. Controversy exists whether it is a primary neoplasm of the kidney or a metastatic neoplasm. The case described is the first reported case of treatment with chemotherapy for a dog with renal lymphosarcoma.