Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Modelos Animales de Enfermedad , Perros , Animales , Enfermedad de Charcot-Marie-Tooth/veterinaria , Enfermedades de los Perros/genética , Neuropatía Hereditaria Motora y Sensorial/genética , Neuropatía Hereditaria Motora y Sensorial/veterinaria , Humanos , MutaciónRESUMEN
Canine inherited neuropathies form a group of degenerative diseases affecting motor and/or sensory and autonomic peripheral nerves. There is now a large number of inherited motor and sensory neuropathies (IMSN) reported in the veterinary literature, for which clinical, electrophysiological, histopathological and mode of inheritance data are available. Their resemblance with Charcot-Marie-Tooth disease in humans is suggested, although direct comparison is difficult due to the small number of cases described in each breed and the lack of genetic knowledge in dogs. Charcot-Marie-Tooth disease forms a wide group of hereditary neuropathies for which a genetic mutation is recognised in more than 70% of patients. In dogs, no genetic mutation has so far been identified and the knowledge available for human hereditary neuropathies may be useful to identify genetic mutations in dogs. This review provides an update on data available on inherited neuropathy in Leonberger dogs and three new degenerative neuropathies are briefly described in two Russian Black terriers, two Cocker Spaniels and a Podhale Shepherd dog.
Asunto(s)
Enfermedades de los Perros/genética , Neuropatía Hereditaria Motora y Sensorial/veterinaria , Animales , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/veterinaria , Perros , Neuropatía Hereditaria Motora y Sensorial/genética , Humanos , MutaciónRESUMEN
A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation.
Asunto(s)
Enfermedades de los Perros/diagnóstico , Neuropatía Hereditaria Motora y Sensorial/veterinaria , Animales , Ataxia/etiología , Ataxia/veterinaria , Enfermedades de los Perros/genética , Enfermedades de los Perros/patología , Perros , Resultado Fatal , Femenino , Predisposición Genética a la Enfermedad , Neuropatía Hereditaria Motora y Sensorial/complicaciones , Neuropatía Hereditaria Motora y Sensorial/diagnóstico , Neuropatía Hereditaria Motora y Sensorial/patologíaAsunto(s)
Anomalías Múltiples/genética , Axones/patología , Cromosomas Humanos Par 16/genética , Proteínas del Citoesqueleto/genética , Cabello/patología , Neuropatía Hereditaria Motora y Sensorial/genética , Proteínas del Tejido Nervioso/genética , Enfermedades Neurodegenerativas/genética , Animales , Enfermedad de Charcot-Marie-Tooth/clasificación , Enfermedad de Charcot-Marie-Tooth/genética , Proteínas del Citoesqueleto/química , Proteínas del Citoesqueleto/deficiencia , Enfermedades de los Perros/genética , Perros , Heterogeneidad Genética , Genotipo , Neuropatía Hereditaria Motora y Sensorial/patología , Neuropatía Hereditaria Motora y Sensorial/veterinaria , Humanos , Familia de Multigenes , Proteínas del Tejido Nervioso/deficiencia , Enfermedades Neurodegenerativas/patología , Proteínas de Neurofilamentos/deficiencia , Proteínas de Neurofilamentos/genética , Secuencias Repetitivas de Aminoácido , Relación Estructura-ActividadRESUMEN
Disorganization of the neurofilament network is a prominent feature of several neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy and axonal Charcot-Marie-Tooth disease. Giant axonal neuropathy (GAN, MIM 256850), a severe, autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system, is characterized by neurofilament accumulation, leading to segmental distension of the axons. GAN corresponds to a generalized disorganization of the cytoskeletal intermediate filaments (IFs), to which neurofilaments belong, as abnormal aggregation of multiple tissue-specific IFs has been reported: vimentin in endothelial cells, Schwann cells and cultured skin fibroblasts, and glial fibrillary acidic protein (GFAP) in astrocytes. Keratin IFs also seem to be alterated, as most patients present characteristic curly or kinky hairs. We report here identification of the gene GAN, which encodes a novel, ubiquitously expressed protein we have named gigaxonin. We found one frameshift, four nonsense and nine missense mutations in GAN of GAN patients. Gigaxonin is composed of an amino-terminal BTB (for Broad-Complex, Tramtrack and Bric a brac) domain followed by a six kelch repeats, which are predicted to adopt a beta-propeller shape. Distantly related proteins sharing a similar domain organization have various functions associated with the cytoskeleton, predicting that gigaxonin is a novel and distinct cytoskeletal protein that may represent a general pathological target for other neurodegenerative disorders with alterations in the neurofilament network.
Asunto(s)
Anomalías Múltiples/genética , Axones/patología , Cromosomas Humanos Par 16/genética , Proteínas del Citoesqueleto/genética , Cabello/patología , Neuropatía Hereditaria Motora y Sensorial/genética , Proteínas del Tejido Nervioso/genética , Enfermedades Neurodegenerativas/genética , Alelos , Secuencia de Aminoácidos , Enfermedad de Charcot-Marie-Tooth/clasificación , Enfermedad de Charcot-Marie-Tooth/genética , Proteínas del Citoesqueleto/química , Proteínas del Citoesqueleto/deficiencia , Proteínas del Citoesqueleto/fisiología , Análisis Mutacional de ADN , ADN Complementario/genética , Exones/genética , Mutación del Sistema de Lectura , Heterogeneidad Genética , Genotipo , Neuropatía Hereditaria Motora y Sensorial/patología , Neuropatía Hereditaria Motora y Sensorial/veterinaria , Humanos , Datos de Secuencia Molecular , Familia de Multigenes , Proteínas del Tejido Nervioso/deficiencia , Enfermedades Neurodegenerativas/patología , Proteínas de Neurofilamentos/deficiencia , Proteínas de Neurofilamentos/genética , Mutación Puntual , Estructura Terciaria de Proteína , Secuencias Repetitivas de Aminoácido , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Relación Estructura-ActividadRESUMEN
A polyneuropathy recognized in mature Rottweiler dogs is characterized by paraparesis that progresses to tetraparesis, spinal hyporeflexia and hypotonia, and appendicular muscle atrophy. Although signs may appear acutely, the course tends to be gradually progressive (up to 12 months or longer in some dogs) and may be relapsing. Nerve and muscle biopsies were examined from eight affected Rottweilers (six male and two female) between ages 1.5 and 4 years. Pronounced neurogenic atrophy was present in skeletal muscle samples. Changes in sensory and motor peripheral nerves included loss of myelinated nerve fibers, axonal necrosis, and variable numbers of fibers with inappropriately thin myelin sheaths. Ultrastructural findings included myelinated fibers showing myelinoaxonal necrosis, demyelinated fibers often associated with macrophage infiltration, many axons with myelin-like membranous profiles, increased endoneurial collagen, occasional axonal atrophy, and numerous Büngner bands. Lesions in unmyelinated fibers included increased numbers of Schwann cell profiles and loss of axons in Schwann cell subunits. Morphologic and morphometric studies indicated preferential loss of medium (5.5-8 microns) and large (8.5-12.5 microns) fibers, which was more severe in distal parts of nerves than in more proximal regions and nerve roots. The cause was not determined; however, histopathologic studies suggest this condition is a dying-back distal sensorimotor polyneuropathy that has morphologic and morphometric similarities to hereditary motor and sensory neuropathy (HMSN) type II in humans.
Asunto(s)
Enfermedades de los Perros/patología , Enfermedades Neuromusculares/veterinaria , Animales , Perros , Femenino , Neuropatía Hereditaria Motora y Sensorial/veterinaria , Masculino , Enfermedades Neuromusculares/patología , Paresia/patología , Paresia/veterinaria , Especificidad de la EspecieRESUMEN
Three aged (10-year-old) German Shepherd Dog litter mates, separately reared, were affected with familial and adult onset peripheral neuropathy. They developed clinical signs, unsteady gait of their hind legs with progressive muscular weakness at almost the same time. The main lesions were systemic neurogenic muscular atrophy, segmental demyelination and Wallerian degeneration of the peripheral nerve fibres. Histochemically, collateral ramification and multiple terminal arborization were observed in terminal axons of motor neurones in the muscles. These changes were attributed to a dying-back process.
Asunto(s)
Enfermedades de los Perros/genética , Neuropatía Hereditaria Motora y Sensorial/veterinaria , Animales , Atrofia , Axones/patología , Enfermedades de los Perros/sangre , Enfermedades de los Perros/patología , Perros , Enzimas/sangre , Femenino , Neuropatía Hereditaria Motora y Sensorial/sangre , Neuropatía Hereditaria Motora y Sensorial/genética , Neuropatía Hereditaria Motora y Sensorial/patología , Hipertrofia , Lípidos/sangre , Masculino , Músculos/patología , Vaina de Mielina/patología , Nervios Periféricos/patología , Degeneración WallerianaRESUMEN
Dystonia musculorum in mice is a hereditary autosomal recessive disorder, characterized by a progressive neuromuscular incoordination. This paper describes the ultrastructural changes in the spinal cord and compares and correlates the results with changes in the spinal ganglia in dystonic mice. Ganglion cells exhibited various stages of degeneration and pyknosis. The dorsal roots of the spinal nerves showed severe degeneration and loss of myelinated fibres accompanied by fibrosis, whilst the ventral roots appeared normal. Nerve cells within the dorsal and intermediate grey matter (laminae I to VII) of the spinal cord showed chromatolysis, atrophy, and necrosis. Boutons exhibited glycogen accumulation or an increase in their electron density. Axonal changes consisted of focal swellings, marked accumulation of neurofilaments, membranous and dense bodies, and disintegration of axoplasm. Myelin sheath degeneration of Wallerian type and degenerating axons were prominent in the dorsal, lateral and ventral white columns of the spinal cord. Glial reactions in the spinal cord were limited to mild hypertrophy and hyperplasia of astrocytic processes. The process of phagocytic activity was not intense in spite of the presence of an abundance of degenerating myelin and cell debris. This study showed that the ultrastructural changes in the spinal cord are more severe than those seen with routine light microscopy. The detection of definite neuronal degeneration of the dorsal root ganglia and spinal cord suggests that the defect apparently operates at the level of cell bodies, as well as axons, of the primary and second order sensory neurons.