RESUMO
BACKGROUND: No definitive, antemortem diagnostic test for canine degenerative myelopathy (DM) is available. Phosphorylated neurofilament heavy (pNF-H) is a promising biomarker for nervous system diseases. HYPOTHESIS/OBJECTIVE: Cerebrospinal fluid (CSF) and serum pNF-H is a detectable biological marker for diagnosis of canine DM. ANIMALS: Fifty-three DM-affected, 27 neurologically normal, 7 asymptomatic at-risk, and 12 DM mimic dogs. METHODS: Archived CSF and serum pNF-H concentrations were determined by a commercially available ELISA. A receiver-operating characteristic (ROC) curve was generated with CSF values. RESULTS: Compared with old control dogs, median CSF pNF-H concentration was increased in all stages of DM; old dogs 5.1 ng/mL (interquartile range [IQR] 1.4-9.3) versus DM stage 1 23.9 ng/mL (IQR 20.8-29.6; P < .05) versus DM stage 2 36.8 ng/mL (IQR 22.9-51.2; P < .0001) versus DM stage 3 25.2 ng/mL (IQR 20.2-61.8; P < .001) versus DM stage 4 38.0 ng/mL (IQR 11.6-59.9; P < .01). Degenerative myelopathy stage 1 dogs had increased median CSF pNF-H concentrations compared with asymptomatic, at-risk dogs (3.4 ng/mL [IQR 1.5-10.9; P < .01]) and DM mimics (6.6 ng/mL [IQR 3.0-12.3; P < .01]). CSF pNF-H concentration >20.25 ng/mL was 80.4% sensitive (confidence interval [CI] 66.09-90.64%) and 93.6% specific (CI 78.58-99.21%) for DM. Area under the ROC curve was 0.9467 (CI 0.92-0.9974). No differences in serum pNF-H concentration were found between control and DM-affected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: pNF-H concentration in CSF is a sensitive biomarker for diagnosis of DM. Although there was high specificity for DM in this cohort, further study should focus on a larger cohort of DM mimics, particularly other central and peripheral axonopathies.
Assuntos
Doenças do Cão/líquido cefalorraquidiano , Doenças Neurodegenerativas/veterinária , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Doenças da Medula Espinal/veterinária , Animais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Doenças do Cão/sangue , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/líquido cefalorraquidiano , Fosforilação , Curva ROC , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/líquido cefalorraquidianoRESUMO
CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system.
Assuntos
Aminopeptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Terapia Genética , Doenças por Armazenamento dos Lisossomos/terapia , Lipofuscinoses Ceroides Neuronais/terapia , Serina Proteases/genética , Aminopeptidases/uso terapêutico , Animais , Dependovirus , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêutico , Modelos Animais de Doenças , Cães , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Vetores Genéticos/uso terapêutico , Humanos , Infusões Intraventriculares , Doenças por Armazenamento dos Lisossomos/genética , Lipofuscinoses Ceroides Neuronais/genética , Neurônios/metabolismo , Neurônios/patologia , Serina Proteases/uso terapêutico , Tripeptidil-Peptidase 1RESUMO
BACKGROUND: Neurodegenerative diseases are a heterogeneous group of disorders characterized by loss of neurons and are commonly associated with a genetic mutation. HYPOTHESIS/OBJECTIVES: To characterize the clinical and histopathological features of a novel degenerative neurological disease affecting the brain of young adult Nova Scotia Duck Tolling Retrievers (NSDTRs). ANIMALS: Nine, young adult, related NSDTRs were evaluated for neurological dysfunction and rapid eye movement sleep behavior disorder. METHODS: Case series review. RESULTS: Clinical signs of neurological dysfunction began between 2 months and 5 years of age and were progressive in nature. They were characterized by episodes of marked movements during sleep, increased anxiety, noise phobia, and gait abnormalities. Magnetic resonance imaging documented symmetrical, progressively increasing, T2-weighted image intensity, predominantly within the caudate nuclei, consistent with necrosis secondary to gray matter degeneration. Abnormalities were not detected on clinicopathological analysis of blood and cerebrospinal fluid, infectious disease screening or urine metabolite screening in most cases. Postmortem examination of brain tissue identified symmetrical malacia of the caudate nuclei and axonal dystrophy within the brainstem and spinal cord. Genealogical analysis supports an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: A degenerative encephalopathy was identified in young adult NSDTRs consistent with a hereditary disease. The prognosis is guarded due to the progressive nature of the disease, which is minimally responsive to empirical treatment.
Assuntos
Encefalopatias/veterinária , Doenças do Cão/diagnóstico , Transtornos Heredodegenerativos do Sistema Nervoso/veterinária , Transtorno do Comportamento do Sono REM/veterinária , Animais , Encefalopatias/genética , Encefalopatias/patologia , Doenças do Cão/genética , Doenças do Cão/patologia , Cães , Feminino , Predisposição Genética para Doença , Transtornos Heredodegenerativos do Sistema Nervoso/diagnóstico , Transtornos Heredodegenerativos do Sistema Nervoso/patologia , Masculino , Linhagem , Transtorno do Comportamento do Sono REM/genética , Transtorno do Comportamento do Sono REM/patologiaRESUMO
BACKGROUND: A variety of presumed hereditary, neurologic diseases have been reported in young Rottweilers. Overlapping ages of onset and clinical signs have made antemortem diagnosis difficult. One of these diseases, neuronal vacuolation and spinocerebellar degeneration (NVSD) shares clinical and histological features with polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV), a recently described hereditary disease in Black Russian Terriers (BRTs). Dogs with POANV harbor mutations in RAB3GAP1 which codes for a protein involved in membrane trafficking. HYPOTHESIS: Rottweilers with NVSD will be homozygous for the RAB3GAP1:c.743delC allele associated with POANV in BRTs. ANIMALS: Eight Rottweilers with NVSD confirmed at necropsy, 128 Rottweilers without early onset neurologic signs, and 468 randomly selected dogs from 169 other breeds. METHODS: Retrospective case-control study. Dogs were genotyped for the RAB3GAP1:c.743delC allele with an allelic discrimination assay. RESULTS: All 8 NVSD-affected dogs were homozygous for the RAB3GAP1:c.743delC allele while the 128 NVSD-free Rottweilers were either homozygous for the reference allele (n = 105) or heterozygous (n = 23) and the 468 genotyped dogs from other breeds were all homozygous for the reference allele. CONCLUSIONS AND CLINICAL IMPORTANCE: The RAB3GAP1:c.743delC mutation is associated with a similar phenotype in Rottweilers and BRTs. Identification of the mutation permits a DNA test that can aid in the diagnosis of NVSD and identify carriers of the trait so that breeders can avoid producing affected dogs. Disruption of membrane trafficking could explain the neuronal vacuolation seen in NVSD and other spongiform encephalopathies.
Assuntos
Doenças do Cão/genética , Degenerações Espinocerebelares/veterinária , Proteínas rab3 de Ligação ao GTP/genética , Animais , Doenças do Cão/patologia , Cães , Genótipo , Mutação , Neurônios/patologia , Polineuropatias/genética , Polineuropatias/patologia , Polineuropatias/veterinária , Estudos Retrospectivos , Degenerações Espinocerebelares/genética , Degenerações Espinocerebelares/patologiaRESUMO
Global ship-based programs, with highly accurate, full water column physical and biogeochemical observations repeated decadally since the 1970s, provide a crucial resource for documenting ocean change. The ocean, a central component of Earth's climate system, is taking up most of Earth's excess anthropogenic heat, with about 19% of this excess in the abyssal ocean beneath 2,000 m, dominated by Southern Ocean warming. The ocean also has taken up about 27% of anthropogenic carbon, resulting in acidification of the upper ocean. Increased stratification has resulted in a decline in oxygen and increase in nutrients in the Northern Hemisphere thermocline and an expansion of tropical oxygen minimum zones. Southern Hemisphere thermocline oxygen increased in the 2000s owing to stronger wind forcing and ventilation. The most recent decade of global hydrography has mapped dissolved organic carbon, a large, bioactive reservoir, for the first time and quantified its contribution to export production (â¼20%) and deep-ocean oxygen utilization. Ship-based measurements also show that vertical diffusivity increases from a minimum in the thermocline to a maximum within the bottom 1,500 m, shifting our physical paradigm of the ocean's overturning circulation.
Assuntos
Carbono/análise , Água do Mar/química , Clima , Oceanografia/instrumentação , Navios , Temperatura , Movimentos da ÁguaRESUMO
BACKGROUND: Juvenile-onset spinocerebellar ataxia has been recognized in Jack Russell Terriers and related Russell group terriers (RGTs) for over 40 years. Ataxia occurs with varying combinations of myokymia, seizures, and other signs of neurologic disease. More than 1 form of the disease has been suspected. HYPOTHESIS/OBJECTIVES: The objective was to identify the mutation causing the spinocerebellar ataxia associated with myokymia, seizures, or both and distinguish the phenotype from other ataxias in the RGTs. ANIMALS: DNA samples from 16 RGTs with spinocerebellar ataxia beginning from 2 to 12 months of age, 640 control RGTs, and 383 dogs from 144 other breeds along with the medical records of affected dogs were studied. METHODS: This case-control study compared the frequencies of a KCNJ10 allele in RGTs with spinocerebellar ataxia versus control RGTs. This allele was identified in a whole-genome sequence of a single RGT with spinocerebellar ataxia and myokymia by comparison to whole-genome sequences from 81 other canids that were normal or had other diseases. RESULTS: A missense mutation in the gene coding for the inwardly rectifying potassium channel Kir4.1 (KCNJ10:c.627C>G) was significantly (P < .001) associated with the disease. Dogs homozygous for the mutant allele all had spinocerebellar ataxia with varying combinations of myokymia and seizures. CONCLUSIONS AND CLINICAL IMPORTANCE: Identification of the KCNJ10 mutation in dogs with spinocerebellar ataxia with myokymia, seizures, or both clarifies the multiple forms of ataxia seen in these breeds and provides a DNA test to identify carriers.
Assuntos
Doenças do Cão/genética , Mutação de Sentido Incorreto/genética , Mioquimia/veterinária , Canais de Potássio Corretores do Fluxo de Internalização/genética , Convulsões/veterinária , Ataxias Espinocerebelares/veterinária , Alelos , Animais , Estudos de Casos e Controles , Cães , Feminino , Predisposição Genética para Doença/genética , Homozigoto , Masculino , Mioquimia/genética , Convulsões/genética , Ataxias Espinocerebelares/genéticaRESUMO
BACKGROUND: Previous reports associated 2 mutant SOD1 alleles (SOD1:c.118A and SOD1:c.52T) with degenerative myelopathy in 6 canine breeds. The distribution of these alleles in other breeds has not been reported. OBJECTIVE: To describe the distribution of SOD1:c.118A and SOD1:c.52T in 222 breeds. ANIMALS: DNA from 33,747 dogs was genotyped at SOD1:c.118, SOD1:c.52, or both. Spinal cord sections from 249 of these dogs were examined. METHODS: Retrospective analysis of 35,359 previously determined genotypes at SOD1:c.118G>A or SOD1:c.52A>T and prospective survey to update the clinical status of a subset of dogs from which samples were obtained with a relatively low ascertainment bias. RESULTS: The SOD1:c.118A allele was found in cross-bred dogs and in 124 different canine breeds whereas the SOD1:c.52T allele was only found in Bernese Mountain Dogs. Most of the dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A homozygotes, but 8 dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A/G heterozygotes and had no other sequence variants in their SOD1 amino acid coding regions. The updated clinical conditions of dogs from which samples were obtained with a relatively low ascertainment bias suggest that SOD1:c.118A homozygotes are at a much higher risk of developing degenerative myelopathy than are SOD1:c.118A/G heterozygotes. CONCLUSIONS AND CLINICAL IMPORTANCE: We conclude that the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs. We also conclude that breeding to avoid the production of SOD1:c.118A homozygotes is a rational strategy.
Assuntos
Doenças do Cão/genética , Atrofia Muscular Espinal/veterinária , Superóxido Dismutase/genética , Alelos , Animais , Cães/genética , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Homozigoto , Atrofia Muscular Espinal/genética , Mutação de Sentido Incorreto , Especificidade da EspécieRESUMO
The focus of immunohistochemistry as applied to nervous system tumors is in identifying the neoplasm present and evaluating margins between normal and neoplastic tissue. Although not always utilized by specialists in neuropathology, immunohistochemistry remains useful to resolve concerns about the differentiation and rate of tumor growth. The aims of this review are to discuss the utility of immunohistochemical reagents currently used in diagnosis of canine and feline intracalvarial tumors, to indicate the applicability of some tests currently used in human nervous system tumors for domestic species, and to evaluate a few less commonly used reagents. A panel of biomarkers is usually needed to confirm a diagnosis, with groups of reagents for leptomeningeal, intraparenchymal, and ventricular neoplasms. In the future, signature genetic alterations found among feline and canine brain tumors--as correlated prospectively with diagnosis, rate of enlargement, or response to treatment--may result in new immunohistochemical reagents to simplify the task of diagnosis. Prospective studies determining the type and proportion of stem cell marker expression on patient longevity are likely to be fruitful and suggest new therapies. Due to increased frequency of biopsy or partial resection of tumors from the living patient, biomarkers are needed to serve as accurate prognostic indicators and assist in determining the efficacy of developing therapeutic options in nervous system tumors of dogs and cats.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Encéfalo/patologia , Doenças do Gato/diagnóstico , Doenças do Cão/diagnóstico , Imuno-Histoquímica/veterinária , Animais , Anticorpos , Biópsia , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Doenças do Gato/metabolismo , Gatos , Doenças do Cão/metabolismo , Cães , Imuno-Histoquímica/métodos , PrognósticoRESUMO
A study was conducted to evaluate the potential association between Ca status at calving and postpartum energy balance, liver lipid infiltration, disease occurrence, milk yield and quality parameters, and fertility in Holstein cows. One hundred cows were assigned to 1 of 2 groups based on whole-blood ionized Ca concentration ([iCa]) on the day of calving [d 0; hypocalcemic [iCa] <1.0 mmol/L (n=51); normocalcemic [iCa] ≥ 1.0 mmol/L (n=49)]. Cows were blocked based on calving date and parity. Blood samples were collected approximately 14 d from expected calving date (d -14), the day of calving (d 0), and on d 3, 7, 14, 21, and 35 postpartum for measurement of plasma nonesterified fatty acid, iCa, total Ca, glucose, and total and direct bilirubin concentrations, and plasma aspartate aminotransferase and gamma glutamyl transferase activities. Liver biopsies were obtained from a subset of cows on d 0, 7, and 35 for quantification of lipid content. Milk samples were collected on d 3, 7, 14, 21, and 35 postpartum for measurement of somatic cell count and percentages of protein, fat, and solids-not-fat. Data for peak test-day milk yield, services per conception, and days open were obtained from Dairy Herd Improvement Association herd records. Disease occurrence was determined based on herd treatment records. Hypocalcemic cows had significantly higher nonesterified fatty acids on d 0. Hypocalcemic cows also had significantly more lipid in hepatocytes on d 7 and 35 postpartum. However, no statistically significant differences were observed between groups for plasma aspartate aminotransferase and gamma glutamyl transferase activities or total and direct bilirubin concentrations. Milk protein percentage was lower in hypocalcemic cows on d 21 and 35. However other milk quality variables (somatic cell count, milk fat percentage, and solids-not-fat) and milk yield variables (peak test-day milk yield and 305-d mature-equivalent 4% fat-corrected milk yield) did not differ between groups. No differences were observed between groups in the occurrence of clinical mastitis, ketosis, displaced abomasum, dystocia, retained placenta, metritis, or fertility measures (percentage cycling at 50-60 d postpartum, services per conception, or days open). These data suggest that early lactation fatty acid metabolism differs between cows with subclinical hypocalcemia and their normocalcemic counterparts.
Assuntos
Doenças dos Bovinos/fisiopatologia , Fertilidade , Hipocalcemia/veterinária , Metabolismo dos Lipídeos/fisiologia , Transtornos Puerperais/veterinária , Animais , Bilirrubina/sangue , Cálcio/sangue , Bovinos , Doenças dos Bovinos/sangue , Contagem de Células , Ácidos Graxos não Esterificados/sangue , Feminino , Glucose/metabolismo , Hipocalcemia/metabolismo , Lactação/fisiologia , Lipídeos/análise , Fígado/química , Fígado/metabolismo , Leite/química , Leite/citologia , Proteínas do Leite/análise , Gravidez , Transtornos Puerperais/sangue , Transtornos Puerperais/fisiopatologiaRESUMO
Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l small hairpin RNA (shRNA), (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA+KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). Mothers were injected with 5-bromo-2-deoxyuridine (BrdU) at either E13.5, E15.5, or E17.5. Disruption of Kiaa0319l function (by knockdown, overexpression, or rescue) resulted in the formation of large nodular periventricular heterotopia in approximately 25% of the rats, which can be seen as early as postnatal day 1. Only a small subset of heterotopic neurons had been transfected, indicating non-cell autonomous effects of the transfection. Most heterotopic neurons were generated in mid- to late-gestation, and laminar markers suggest that they were destined for upper cortical laminae. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminae. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia.
Assuntos
Córtex Cerebral/crescimento & desenvolvimento , Dislexia/genética , Regulação da Expressão Gênica no Desenvolvimento , Malformações do Desenvolvimento Cortical do Grupo II/genética , Células-Tronco Neurais/metabolismo , Proteínas Nucleares/metabolismo , Animais , Animais Recém-Nascidos , Suscetibilidade a Doenças , Eletroporação , Humanos , Neurogênese/genética , Proteínas Nucleares/genética , RNA Interferente Pequeno , Ratos , Ratos Transgênicos , Receptores de Superfície Celular , TransfecçãoRESUMO
Inherited osteopetrosis was identified in cattle herds in Wyoming, Nebraska, and Missouri in 2008 to 2010. Ten affected Red Angus calves were examined to characterize lesions in brain, teeth, and skull. Six affected aborted or stillborn calves were homozygous for the recently characterized deletion mutation in SLC4A2. Four affected calves were heterozygous for the SLC4A2 mutation and survived 1 to 7 days after birth. Gross lesions were similar in all 10 calves. Brains were rectangular and dorsoventrally compressed, with concave depressions in the parietal cortex owing to thickened parietal bone. Cerebellar hemispheres were compressed with herniation of the cerebellar vermis into the foramen magnum. Moderate bilateral chromatolysis affected multiple cranial nerve nuclei and, in some calves, the red nucleus. There was loss of retinal ganglion cells with severe atrophy of optic nerves. Periventricular corpora amylacea were in the thalamus, caudate nucleus, and midbrain. Vessels and neuropil in the dorsomedial aspect of the thalamus were mineralized. Dysplastic change in premolar and molar teeth comprised intra-alveolar intermingling of dentin, enamel, cementum, and bone, contributing to dental ankylosis. Changes in the heads of osteopetrotic calves are similar to those in children with malignant forms of homozygous recessive osteopetrosis.
Assuntos
Doenças dos Bovinos/genética , Antiportadores de Cloreto-Bicarbonato/genética , Osteopetrose/veterinária , Aborto Animal , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Bovinos , Doenças dos Bovinos/patologia , Feminino , Heterozigoto , Homozigoto , Masculino , Missouri , Nebraska , Atrofia Óptica/patologia , Atrofia Óptica/veterinária , Osteopetrose/genética , Osteopetrose/patologia , Deleção de Sequência , Crânio/patologia , Dente/patologia , WyomingRESUMO
A 4-year-old dog was presented for acute, progressive tetraparesis and cervical hyperesthesia. Symmetrical tubular structures coursing along the lateroventral aspects of the spinal cord at the fourth and fifth cervical vertebrae were identified in magnetic resonance images. At necropsy, vertebral arteries and their spinal branches were severely ectatic bilaterally, and the cervical spinal cord was compressed. Histologically, the ectatic branches of the vertebral and ventral spinal arteries were surrounded by fibrosis with scant mononuclear cell infiltrates and hemorrhage. Spinal branches of the vertebral arteries had focally severe reduction in the tunica media. A thrombus was in an arterial branch. Smaller vessels in adjacent tissue had fibrinoid degeneration. Axonal degeneration was detected in the affected spinal cord and nerve roots. The segmental degenerative radiculomyelopathy in this dog was attributed to anomalous ectasia of the vertebral and ventral spinal arteries.
Assuntos
Vértebras Cervicais/patologia , Dilatação Patológica/veterinária , Doenças do Cão/etiologia , Compressão da Medula Espinal/veterinária , Artéria Vertebral/patologia , Animais , Vértebras Cervicais/irrigação sanguínea , Dilatação Patológica/complicações , Dilatação Patológica/patologia , Doenças do Cão/patologia , Cães , Fibrose/patologia , Hiperestesia/etiologia , Hiperestesia/patologia , Hiperestesia/veterinária , Imageamento por Ressonância Magnética/veterinária , Masculino , Pescoço/patologia , Radiculopatia/etiologia , Radiculopatia/patologia , Radiculopatia/veterinária , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/patologiaAssuntos
Doenças do Cão/genética , Mutação de Sentido Incorreto/genética , Doenças da Medula Espinal/veterinária , Superóxido Dismutase/genética , Animais , Doenças do Cão/patologia , Cães , Feminino , Medula Espinal/patologia , Doenças da Medula Espinal/genética , Doenças da Medula Espinal/patologia , Superóxido Dismutase-1RESUMO
BACKGROUND: Bandera's neonatal ataxia (BNAt) is an autosomal recessive cerebellar ataxia that affects members of the Coton de Tulear dog breed. OBJECTIVE: To identify the mutation that causes BNAt. ANIMALS: The study involved DNA from 112 Cotons de Tulear (including 15 puppies with signs of BNAt) and 87 DNA samples from dogs of 12 other breeds. METHODS: The BNAt locus was mapped with a genome-wide association study (GWAS). The coding exons of positional candidate gene GRM1, which encodes metabotropic glutamate receptor 1, were polymerase chain reaction (PCR)-amplified and resequenced. A 3-primer PCR assay was used to genotype individual dogs for a truncated retrotransposon inserted into exon 8 of GRM1. RESULTS: The GWAS indicated that the BNAt locus was in a canine chromosome 1 region that contained candidate gene GRM1. Resequencing this gene from BNAt-affected puppies indicated that exon 8 was interrupted by the insertion of a 5'-truncated retrotransposon. All 15 BNAt-affected puppies were homozygous for the insert, whereas all other Cotons de Tulear were heterozygotes (n = 43) or homozygous (n = 54) for the ancestral allele. None of the 87 dogs from 12 other breeds had the insertion allele. CONCLUSIONS AND CLINICAL IMPORTANCE: BNAt is caused by a retrotransposon inserted into exon 8 of GRM1. A DNA test for the GRM1 retrotransposon insert can be used for genetic counseling and to confirm the diagnosis of BNAt.
Assuntos
Ataxia Cerebelar/veterinária , Doenças do Cão/genética , Mutação , Receptores de Glutamato Metabotrópico/genética , Idade de Início , Animais , Ataxia Cerebelar/genética , Análise Mutacional de DNA/veterinária , Primers do DNA/genética , Cães , Éxons , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Heterozigoto , Homozigoto , Masculino , Mutagênese Insercional , Fases de Leitura Aberta , Linhagem , RetroelementosRESUMO
An adult dog with ataxia and a lingual mass, previously diagnosed as protothecosis, was euthanized. At the postmortem examination, the lingual mass, regions of the lungs and hilar lymph nodes, liver, mesenteric and sublumbar lymph nodes, and spinal meninges had pronounced green discoloration. Histologically, pyogranulomatous inflammation and algal organisms were found in the tongue, spinal meninges, hilar and mesenteric lymph nodes, liver, and lung. The algae had cell walls positive for periodic acid-Schiff and cytoplasmic granules. Ultrastructurally, the algae had a well-defined cell wall, stacks of grana and thylakoid membrane, and dense bodies, typical of starch granules. The organisms were identified as Chlorella, a green alga, based on the results of histochemistical and electron microscopic examination. To the author's knowledge this is the first report of disseminated Chlorella infection and the first report in a companion animal.
Assuntos
Chlorella/isolamento & purificação , Doenças do Cão/microbiologia , Infecções/veterinária , Animais , Doenças do Cão/patologia , Cães , Feminino , Infecções/microbiologia , Meninges/microbiologia , Medula Espinal/microbiologia , Medula Espinal/patologia , Língua/microbiologia , Língua/patologiaRESUMO
In a previous study, we characterized the reactivity of monoclonal antibody (MoAb) 8G7G3/1 to thyroid transcription factor-1 (TTF-1) in canine thyroid tumors. In this study, we have examined the reactivity of this antibody in 120 canine pulmonary tumors, including 78 primary epithelial tumors. Tissues had been fixed in formalin and routinely processed for histopathology. Nuclear staining for TTF-1 was detected in 64.2% of primary pulmonary epithelial tumors. The most common TTF-1-reactive tumor types were bronchioloalveolar carcinomas and bronchogenic carcinomas. Staining was diffuse, heterogeneous, or patchy. Nonpulmonary, metastatic epithelial tumors, except two of two thyroid carcinomas, did not react with antibody 8G7G3/1. Mesotheliomas and other mesenchymal tumors were also negative for this marker. A reduction or loss of reactivity was apparent in pulmonary epithelial tumors archived in paraffin blocks for 7-8 years. There was slight reduction in the number of positive cells or the intensity of the reaction in control tissues fixed longer than 1 week. On the basis of our limited studies and the human literature, it appears that MoAb 8G7G3/1 to TTF-1 is a highly specific (with the exception of thyroid tumors) and moderately sensitive marker for canine pulmonary epithelial tumors.
Assuntos
Anticorpos Monoclonais , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Neoplasias Pulmonares/veterinária , Proteínas Nucleares , Fatores de Transcrição , Animais , Diagnóstico Diferencial , Cães , Imuno-Histoquímica/métodos , Imuno-Histoquímica/veterinária , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Sensibilidade e Especificidade , Fator Nuclear 1 de TireoideRESUMO
Immunohistochemistry for uroplakin III (UP III), cytokeratin 7 (CK 7), and cytokeratin 20 (CK 20) using commercially available antibodies was done in normal canine urinary bladder and 72 canine urinary bladder tumors that had been fixed in formalin and embedded in paraffin. Prolonged fixation (3-28 days) did not significantly alter the immunostaining for UP III. There was moderate reduction in the intensity for CK 7 and CK 20 after 1 week of fixation. UP III was detected in superficial (umbrella) cells and some intermediate cells of the normal urinary bladder, 7 of 7 transitional cell papillomas (TCPs), 50 of 55 transitional cell carcinomas (TCCs), and 4 of 5 metastatic TCCs. Staining was typically outlined in the plasma membrane, but diffuse or focal cytoplasmic staining was also observed. Intracytoplasmic lumina were usually positive for UP III. One squamous cell carcinoma of the bladder, 4 nonepithelial bladder tumors, and 285 nonurothelial tumors from different nonurinary locations were negative for UP III. CK 7 was detected in 7 of 7 TCPs, 53 of 54 TCCs, and 5 of 5 metastatic TCCs. The staining for CK 7 was diffuse cytoplasmic. CK 20 was detected in 1 of 7 TCPs, 37 of 54 TCCs, and 1 of 5 metastatic TCCs. The staining with CK 20 was cytoplasmic and weaker than with antibodies to UP III or CK 7. There was concurrent expression of UP III, CK 7, and CK 20 in 36 of 54 TCCs. UP III is a specific and sensitive marker for canine transitional epithelial (urothelial) neoplasms, detecting 91% of TCCs. Negative results may be observed with anaplastic tumors.
Assuntos
Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/veterinária , Doenças do Cão/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Queratinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/veterinária , Animais , Carcinoma de Células de Transição/patologia , Doenças do Cão/patologia , Cães , Imuno-Histoquímica/veterinária , Queratina-20 , Queratina-7 , Papiloma/metabolismo , Papiloma/patologia , Papiloma/veterinária , Fixação de Tecidos/veterinária , Neoplasias da Bexiga Urinária/patologia , Uroplaquina III , Urotélio/metabolismo , Urotélio/patologiaRESUMO
Immunohistochemistry, using a monoclonal antibody to Melan A and a polyclonal antibody to S100 protein, was applied to 48 formalin-fixed, paraffin-embedded specimens of feline melanoma. Forty-two cutaneous, three oral, one mucocutaneous, and two metastatic melanomas comprised the tumors. Thirty-two tumors (67%) were positive for Melan A and 42 (87.5%) were positive for S100. All but one of the tumors that were positive for Melan A were also positive for S100. S100 was detected in 11 of 16 tumors that were negative for Melan A. Seventy-five percent (9 of 12) of amelanotic melanomas were negative for Melan A. Normal adrenal cortex, the cerebellum, and the skin had cells that were positive for Melan A. Sebaceous adenoma was the only nonmelanocytic tumor examined that reacted with antibody to Melan A. Although less sensitive than S100 protein, Melan A is more specific for melanoma and is useful in differentiating feline cutaneous melanoma from the more common pigmented basal cell tumor.