RESUMEN

Blood parasites are generally uncommon in seabirds, and knowledge on their epidemiology is further limited by the fact that they often inhabit remote locations that are logistically difficult or expensive to study. We present a long term data set of blood smear examinations of 1909 seabirds belonging to 27 species that were admitted to a rehabilitation centre in Cape Town (Western Cape, South Africa) between 2001 and 2013. Blood parasites were detected in 59% of species (16/27) and 29% of individuals examined (551/1909). The following blood parasites were recorded: Babesia ugwidiensis, Babesia peircei, Babesia sp., Plasmodium sp., Leucocytozoon ugwidi, Hepatozoon albatrossi, Haemoproteus skuae and Spirochaetales. Several of the records are novel host-parasite associations, demonstrating the potential of rehabilitation centres for parasite and disease surveillance, particularly for species infrequently sampled from which no host-specific parasites have been described.

Asunto(s)

Enfermedades de las Aves/epidemiología , Enfermedades de las Aves/parasitología , Infecciones Protozoarias en Animales/parasitología , Infecciones por Spirochaetales/veterinaria , Animales , Enfermedades de las Aves/sangre , Enfermedades de las Aves/microbiología , Aves/sangre , Aves/parasitología , Interacciones Huésped-Parásitos , Infecciones Protozoarias en Animales/sangre , Infecciones Protozoarias en Animales/microbiología , Sudáfrica , Spirochaetales/fisiología , Infecciones por Spirochaetales/sangre , Infecciones por Spirochaetales/epidemiología

RESUMEN

Blood profiling is a helpful tool in detecting the health status, metabolic diseases, nutritional deficiencies, and welfare of animals. Body weights, body temperatures, hematological and serum biochemical parameters, enzymes, and electrolytes in both sexes of farm emus at the beginning of their breeding season (November in Canada), were determined. The reference interval for each analyte was also calculated. Emus have lower body temperatures (37.2 ± 0.2) than other poultry species. There was no significant between-sex difference in BW, body temperature, and all the hematological and enzyme parameters measured. However, females had significantly (P < 0.001) higher serum calcium, phosphorus, albumin, total protein, globulin, and triglyceride levels than males, probably in preparation for egg laying. We also examined our findings in light of their sex-role reversal in incubation and brooding. Contrary to other avian species in which only females incubate and brood, there was no sex difference in the hematological and enzyme parameters measured in emus. We found that emus are similar to other ratite species with respect to the changes in protein, globulin, triglyceride, and calcium levels. The findings from our study contribute to the database for reference emu hematological and serum enzyme, metabolite, and electrolyte values.

Asunto(s)

Dromaiidae/fisiología , Crianza de Animales Domésticos , Animales , Análisis Químico de la Sangre/veterinaria , Dromaiidae/sangre , Femenino , Pruebas Hematológicas/veterinaria , Masculino , Valores de Referencia , Reproducción , Saskatchewan

Asunto(s)

Proteínas de Ciclo Celular/genética , ADN Mitocondrial/genética , Eliminación de Gen , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Oftalmoplejía Externa Progresiva Crónica/genética , Ribonucleótido Reductasas/deficiencia , Ribonucleótido Reductasas/genética , Adulto , Factores de Edad , Estudios de Cohortes , Femenino , Humanos , Masculino , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/metabolismo , Oftalmoplejía Externa Progresiva Crónica/diagnóstico , Oftalmoplejía Externa Progresiva Crónica/metabolismo

Asunto(s)

ADN Mitocondrial/genética , ADN Polimerasa Dirigida por ADN/genética , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/patología , alfa-Sinucleína/metabolismo , Southern Blotting , Encéfalo/metabolismo , Encéfalo/patología , Análisis Mutacional de ADN , ADN Polimerasa gamma , Complejo IV de Transporte de Electrones/metabolismo , Humanos , Inmunohistoquímica , Cuerpos de Lewy/patología , Masculino , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Mutación , Vaina de Mielina/patología , Reacción en Cadena de la Polimerasa , Médula Espinal/patología , Canales Aniónicos Dependientes del Voltaje/metabolismo

Asunto(s)

ADN Mitocondrial/genética , Enfermedades Gastrointestinales/genética , Enfermedades Gastrointestinales/fisiopatología , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/fisiopatología , Mutación Puntual/genética , Adenina/metabolismo , Adulto , Secuencia de Bases/genética , Análisis Mutacional de ADN , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Metabolismo Energético/genética , Resultado Fatal , Femenino , Enfermedades Gastrointestinales/metabolismo , Motilidad Gastrointestinal/genética , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/fisiopatología , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Guanina/metabolismo , Humanos , Síndrome MELAS/genética , Síndrome MELAS/fisiopatología , Persona de Mediana Edad , Mitocondrias/genética , Mitocondrias/metabolismo , Enfermedades Mitocondriales/metabolismo , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología

RESUMEN

BACKGROUND: In clinical practice, mitochondrial disease is seldom considered until a variable combination of seizures, alteration in tone, muscle weakness, and developmental problems is evident. However, it is not uncommon for one symptom to occur in isolation and dominate the clinical phenotype. We report six patients from two families where dystonia was the principal clinical manifestation. A mitochondrial etiology was considered in each case because of the association of dystonia with other less prominent clinical features such as epilepsy. METHODS: Histochemical and biochemical analyses were undertaken in skeletal muscle biopsies from individuals in both families. Sequencing of skeletal muscle mtDNA was also performed and suspected mutations were quantified by hot last cycle PCR-RFLP or primer extension assay. Functional consequences of one of the mutations were investigated by measurement of steady state levels of mitochondrial tRNA. RESULTS: Two distinct mitochondrial pathologies were identified: a novel, homoplasmic mitochondrial tRNA(Cys) (MTTC) mutation and the primary, m.11778G>A Leber hereditary optic neuropathy (LHON) mutation. The mild nature of both mutations has permitted very high levels of mutated mtDNA to accumulate. Patients with the mutation in the MTTC gene have no wild type mtDNA detectable and although the LHON mutation is heteroplasmic in the patients we report, it is commonly observed to be homoplasmic. CONCLUSIONS: The mitochondrial etiology identified in these patients emphasizes the pathologic potential of homoplasmic mutations and has important implications for the investigation and genetic counseling of families where dystonia is the principal clinical feature. We advocate that mitochondrial disease should be given serious consideration in patients with familial, progressive dystonia, particularly when additional neurologic features such as epilepsy are present.

Asunto(s)

ADN Mitocondrial/genética , Distonía/genética , Predisposición Genética a la Enfermedad/genética , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/genética , Mutación/genética , Adulto , Ganglios Basales/patología , Ganglios Basales/fisiopatología , Enfermedades de los Ganglios Basales/genética , Enfermedades de los Ganglios Basales/patología , Enfermedades de los Ganglios Basales/fisiopatología , Análisis Mutacional de ADN , Diagnóstico Diferencial , Distonía/fisiopatología , Epilepsia/genética , Epilepsia/fisiopatología , Femenino , Pruebas Genéticas , Genotipo , Humanos , Patrón de Herencia/genética , Masculino , Persona de Mediana Edad , Enfermedades Mitocondriales/fisiopatología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Atrofia Óptica Hereditaria de Leber/genética , Linaje , ARN de Transferencia/genética

RESUMEN

AIMS/HYPOTHESIS: The aims of this study were (1) to determine the prevalence and rate of progression in diabetes secondary to mitochondrial DNA (mtDNA) mutations; and (2) to determine whether percentage heteroplasmy predicts clinical outcome in patients carrying the m.3243A>G mutation. METHODS: We prospectively assessed 242 patients attending a specialist neuromuscular clinic using a validated mitochondrial disease rating scale. Retrospective clinical data on these patients from up to 25 years of follow-up were also included. Percentage heteroplasmy in blood, urine and muscle was determined for the m.3243A>G group and correlated against clinical features. RESULTS: Patients carrying the m.3243A>G mutation formed the largest group of patients with diabetes (31/81 patients). The highest prevalence of diabetes was in the m.12258C>A group (2/2 patients), the lowest in the multiple mtDNA deletions group (3/43 patients). The earliest age of onset was in the m.3243A>G group (37.9 years) with the highest age of presentation in the multiple deletion group (56.3 years). Of patients presenting with m.3243A>G, 12.9% required insulin; an additional 32.3% progressed to insulin requirement over a mean of 4.2 years after presentation. Percentage heteroplasmy in blood, urine or muscle did not predict progression of diabetes or risk of developing complications. Early age of presentation with diabetes did predict poor clinical outcome. CONCLUSIONS/INTERPRETATION: Although patients carrying the m.3243A>G mutation account for the majority of cases of diabetes secondary to mtDNA mutations, several other genotypes are also associated with the development of diabetes, some with high penetrance. All show a gradual progression to insulin requirement. Percentage heteroplasmy is a poor predictor of severity of diabetes in the m.3243A>G group.

Asunto(s)

ADN Mitocondrial/genética , Complicaciones de la Diabetes/epidemiología , Enfermedades Mitocondriales/epidemiología , Complicaciones de la Diabetes/genética , Progresión de la Enfermedad , Humanos , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/fisiopatología , Mutación , Polimorfismo de Nucleótido Simple , Prevalencia

RESUMEN

Mitochondrial diseases affect all age groups, but those with childhood onset often seem to experience the greatest burden of disability. In some paediatric patients this can be explained by a cumulative disability acquired over many years. In others, additional factors, including the nature and severity of the molecular defect, must be considered. To date, no large-scale studies have attempted to document the natural history of paediatric mitochondrial disease. This is in part at least, because no assessment tool has been available to plot the temporal course of a disease with such a diverse clinical spectrum. This paper describes how a practical and semi-quantitative rating scale has been devised for children with mitochondrial disease, the Newcastle paediatric mitochondrial disease scale (NPMDS). The scale is multi-dimensional and reproducible, offering a tool through which mitochondrial disease progression can be objectively monitored. We anticipate that use of this tool will facilitate both longitudinal natural history studies and the assessment of future therapeutic interventions.

Asunto(s)

Evaluación de la Discapacidad , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/terapia , Encefalomiopatías Mitocondriales/diagnóstico , Encefalomiopatías Mitocondriales/terapia , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Neurología/métodos , Variaciones Dependientes del Observador , Pediatría/métodos , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Reino Unido

RESUMEN

Mitochondrial DNA (mtDNA) disease is an important genetic cause of neurological disability. A variety of different clinical features are observed and one of the most common phenotypes is MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes). The majority of patients with MELAS have the 3243A>G mtDNA mutation. The neuropathology is dominated by multifocal infarct-like lesions in the posterior cortex, thought to underlie the stroke-like episodes seen in patients. To investigate the relationship between mtDNA mutation load, mitochondrial dysfunction and neuropathological features in MELAS, we studied individual neurones from several brain regions of two individuals with the 3243A>G mutation using dual cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) histochemistry, and Polymerase Chain Reaction Restriction Fragment Lenght Polymorphism (PCR-RFLP) analysis. We found a low number of COX-deficient neurones in all brain regions. There appeared to be no correlation between the threshold level for the 3243A>G mutation to cause COX deficiency within single neurones and the degree of pathology in affected brain regions. The most severe COX deficiency associated with the highest proportion of mutated mtDNA was present in the walls of the leptomeningeal and cortical blood vessels in all brain regions. We conclude that vascular mitochondrial dysfunction is important in the pathogenesis of the stroke-like episodes in MELAS patients. As migraine is a commonly encountered feature in MELAS, we propose that coupling of the vascular mitochondrial dysfunction with cortical spreading depression (CSD) might underlie the selective distribution of ischaemic lesions in the posterior cortex in these patients.

Asunto(s)

Vasos Sanguíneos/patología , Encéfalo/patología , Síndrome MELAS/patología , Neurobiología , Neuronas/patología , Adulto , Vasos Sanguíneos/metabolismo , ADN Mitocondrial/genética , Complejo IV de Transporte de Electrones/metabolismo , Femenino , Humanos , Inmunohistoquímica , Síndrome MELAS/complicaciones , Persona de Mediana Edad , Trastornos Migrañosos/etiología , Trastornos Migrañosos/fisiopatología , Mutación , Polimorfismo de Longitud del Fragmento de Restricción , Succinato Deshidrogenasa/metabolismo

RESUMEN

The natural history of mitochondrial diseases is poorly understood, limiting our ability to offer prognostic advice to patients or to evaluate therapy. One major obstacle to improving our understanding is the lack of a clinical rating scale to monitor the extensive clinical spectrum of mitochondrial disease. In this article, the authors describe the development and validation of a practical and semiquantitative rating scale, the Newcastle Mitochondrial Disease Adult Scale.

Asunto(s)

Indicadores de Salud , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/terapia , Evaluación de Resultado en la Atención de Salud/métodos , Calidad de Vida , Encuestas y Cuestionarios , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del Tratamiento

RESUMEN

The authors sequenced POLG1, C10ORF2, and ANT1 in 38 sporadic progressive external ophthalmoplegia patients with multiple mitochondrial DNA (mtDNA) deletions. Causative mutations were identified in approximately 10% of cases, with two unrelated individuals harboring a novel premature stop codon mutation (1356T>G). None had a mutation in C10ORF2 or ANT1. In the majority of patients, the primary nuclear genetic defect is likely to affect other unknown genes important for mtDNA maintenance.

Asunto(s)

Translocador 1 del Nucleótido Adenina/genética , ADN Primasa/genética , ADN Mitocondrial/genética , ADN Polimerasa Dirigida por ADN/genética , Oftalmoplejía Externa Progresiva Crónica/genética , Eliminación de Secuencia , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Southern Blotting , Estudios de Cohortes , Sistemas de Computación , ADN Helicasas , Análisis Mutacional de ADN , ADN Polimerasa gamma , Reacciones Falso Negativas , Femenino , Predisposición Genética a la Enfermedad , Alemania , Humanos , Masculino , Miopatías Mitocondriales/genética , Proteínas Mitocondriales , Datos de Secuencia Molecular , Fenotipo , Mutación Puntual , Reacción en Cadena de la Polimerasa/métodos , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Reino Unido

RESUMEN

Mitochondrial DNA (mtDNA) disease is a common cause of myopathy and the presence of histochemically demonstrated cytochrome c oxidase (COX) deficiency is an extremely useful diagnostic feature. However, there is currently no quantitative information regarding the variability of COX deficiency within or between muscles. This study addresses this issue by studying a number of skeletal muscle samples obtained at post-mortem from three patients with mitochondrial disease due to established mitochondrial DNA defects. COX deficient muscle fibres were enumerated in sections of these muscles and analysed according to patient, individual muscle, position within a particular muscle and sample size. Descriptive statistics were generated followed by an analysis of variance (ANOVA) to assess the effect of these parameters on the mean percentage of COX deficient fibres. We observed statistically significant variation in the percentage of COX deficient fibres within individual muscles from each patient for samples sizes of between 100 and 400 fibres. Our results have implications for the way in which biopsies of skeletal muscle are used for the assessment of disease severity, progression and response to treatment.

Asunto(s)

Deficiencia de Citocromo-c Oxidasa/complicaciones , Complejo IV de Transporte de Electrones/metabolismo , Miopatías Mitocondriales/enzimología , Miopatías Mitocondriales/etiología , Músculo Esquelético/enzimología , Adulto , Análisis de Varianza , Southern Blotting/métodos , Deficiencia de Citocromo-c Oxidasa/patología , Complejo IV de Transporte de Electrones/genética , Femenino , Histocitoquímica/métodos , Humanos , Masculino , Persona de Mediana Edad , Miopatías Mitocondriales/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos

Asunto(s)

ADN Mitocondrial/genética , Polimorfismo Genético , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/genética , Análisis Mutacional de ADN , Genotipo , Humanos , Reacción en Cadena de la Polimerasa , Factores de Riesgo

RESUMEN

The authors describe a patient who presented with headache, seizures, and severe cerebral edema in whom they identified a novel mutation in the mitochondrial (mt-) tRNA(His) gene. This G12147A transition is heteroplasmic, predicted to disrupt a highly conserved base pair, and segregates with the cytochrome c oxidase deficiency in single muscle fibers.

Asunto(s)

ADN Mitocondrial/genética , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/genética , Mutación , ARN de Transferencia de Histidina/genética , Adulto , Biopsia , Edema Encefálico/etiología , Análisis Mutacional de ADN , Progresión de la Enfermedad , Complejo IV de Transporte de Electrones/metabolismo , Cefalea/etiología , Humanos , Masculino , Enfermedades Mitocondriales/complicaciones , Datos de Secuencia Molecular , Fibras Musculares de Contracción Rápida/química , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares de Contracción Rápida/patología , Músculo Esquelético/enzimología , Músculo Esquelético/patología , Conformación de Ácido Nucleico , Atrofia Óptica/etiología , Fenotipo , Síndrome de Reye/complicaciones , Convulsiones/etiología , Homología de Secuencia de Ácido Nucleico

Asunto(s)

ADN Mitocondrial/genética , Oftalmoplejía Externa Progresiva Crónica/genética , Eliminación de Secuencia/genética , Gemelos Monocigóticos/genética , Enfermedades en Gemelos/genética , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Oftalmoplejía Externa Progresiva Crónica/diagnóstico

RESUMEN

To verify the impact of mutations in ANT1, Twinkle, and POLG1 genes in sporadic progressive external ophthalmoplegia associated with multiple mitochondrial DNA (mtDNA) deletions, DNA samples from 15 Italian and 12 British patients were screened. Mutations in ANT1 were found in one patient, in Twinkle in two patients, and in POLG1 in seven patients. Irrespective of the inheritance mode, screening of these genes should be performed in all patients with progressive external ophthalmoplegia with multiple mtDNA deletions.

Asunto(s)

Translocador 1 del Nucleótido Adenina/genética , ADN Primasa/genética , ADN Mitocondrial/genética , ADN Polimerasa Dirigida por ADN/genética , Oftalmoplejía Externa Progresiva Crónica/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Sustitución de Aminoácidos , ADN Helicasas , Análisis Mutacional de ADN , ADN Polimerasa gamma , Inglaterra/epidemiología , Femenino , Genes Recesivos , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Proteínas Mitocondriales , Datos de Secuencia Molecular , Mutación Missense , Oftalmoplejía Externa Progresiva Crónica/epidemiología , Mutación Puntual , Estudios Retrospectivos , Alineación de Secuencia , Eliminación de Secuencia , Homología de Secuencia de Aminoácido

RESUMEN

Mitochondrial disorders represent a multitude of clinically heterogeneous diseases in which the genetic abnormality can involve either a mitochondrial or nuclear gene. In addition to inherited defects, somatic mitochondrial DNA mutations have been implicated in the pathogenesis of neurodegenerative disease, cancer and the ageing process. The recent emergence of the first mouse models of mitochondrial disease will provide valuable insights into disease mechanisms and aid the development of realistic therapeutic strategies.

Asunto(s)

Mitocondrias Musculares/genética , Miopatías Mitocondriales/genética , Envejecimiento/genética , Envejecimiento/fisiología , Animales , ADN Mitocondrial/genética , Genoma Humano , Humanos , Mitocondrias Musculares/fisiología , Miopatías Mitocondriales/fisiopatología , Miopatías Mitocondriales/terapia , Enfermedades Neurodegenerativas/genética

RESUMEN

Little is known about the development of presynaptic specializations. Recent studies that visualize tagged synaptic components in cultured cells and in vivo have identified molecular participants and reveal common features in cellular processes of presynaptic assembly.

Asunto(s)

Sistema Nervioso/crecimiento & desarrollo , Transducción de Señal/fisiología , Sinapsis/fisiología , Animales , Citoesqueleto/genética , Citoesqueleto/fisiología , Humanos , Sistema Nervioso/metabolismo , Transducción de Señal/genética

RESUMEN

The cryptocephal (crc) mutation causes pleiotropic defects in ecdysone-regulated events during Drosophila molting and metamorphosis. Here we report that crc encodes a Drosophila homolog of vertebrate ATF4, a member of the CREB/ATF family of basic-leucine zipper (bZIP) transcription factors. We identified three putative protein isoforms. CRC-A and CRC-B contain the bZIP domain, and CRC-D is a C-terminally truncated form. We have generated seven new crc alleles. Consistent with the molecular diversity of crc, these alleles show that crc is a complex genetic locus with two overlapping lethal complementation groups. Alleles representing both groups were rescued by a cDNA encoding CRC-B. One lethal group (crc(1), crc(R6), and crc(Rev8)) consists of strong hypomorphic or null alleles that are associated with mutations of both CRC-A and CRC-B. These mutants display defects associated with larval molting and pupariation. In addition, they fail to evert the head and fail to elongate the imaginal discs during pupation, and they display variable defects in the subsequent differentiation of the adult abdomen. The other group (crc(R1), crc(R2), crc(E85), crc(E98), and crc(929)) is associated with disruptions of CRC-A and CRC-D; except for a failure to properly elongate the leg discs, these mutants initiate metamorphosis normally. Subsequently, they display a novel metamorphic phenotype, involving collapse of the head and abdomen toward the thorax. The crc gene is expressed throughout development and in many tissues. In third instar larvae, crc expression is high in targets of ecdysone signaling, such as the leg and wing imaginal discs, and in the ring gland, the source of ecdysone. Together, these findings implicate CREB/ATF proteins in essential functions during molting and metamorphosis. In addition, the similarities between the mutant phenotypes of crc and the ecdysone-responsive genes indicate that these genes are likely to be involved in common signaling pathways.

Asunto(s)

Drosophila/genética , Leucina Zippers/genética , Metamorfosis Biológica/genética , Muda/genética , Mutación , Factores de Transcripción/genética , Factores de Transcripción/fisiología , Factor de Transcripción Activador 4 , Alelos , Secuencia de Aminoácidos , Animales , Mapeo Cromosómico , Clonación Molecular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Drosophila/anatomía & histología , Drosophila/fisiología , Ecdisona/metabolismo , Eliminación de Gen , Prueba de Complementación Genética , Modelos Genéticos , Datos de Secuencia Molecular , Mutagénesis , Fenotipo , Filogenia , Isoformas de Proteínas , ARN Mensajero/metabolismo , Homología de Secuencia de Aminoácido , Transducción de Señal , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Transformación Genética

RESUMEN

Little is known of mechanisms regulating presynaptic differentiation. We identified rpm-1 in a screen for mutants with defects in patterning of a presynaptic marker at certain interneuronal synapses. The predicted RPM-1 protein contains zinc binding, RCC1, and other conserved motifs. In rpm-1 mutants, mechanosensory neurons fail to accumulate tagged vesicles, retract synaptic branches, and ectopically extend axons. Some motor neurons branch and overgrow; others show altered synaptic organization. Expression of RPM-1 in the presynaptic mechanosensory neurons is sufficient to rescue phenotypes in these cells. Certain rpm-1 phenotypes are temperature sensitive, revealing that RPM-1 function can be bypassed by maintaining mutants at the permissive temperature at stages commensurate with synapse formation in wild-type animals. These results indicate that RPM-1 functions cell autonomously during synaptogenesis to regulate neuronal morphology.

Asunto(s)

Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiología , Marcación de Gen , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/fisiología , Neuronas/fisiología , Sinapsis/fisiología , Animales , Caenorhabditis elegans/anatomía & histología , Secuencia Conservada/genética , Factores de Intercambio de Guanina Nucleótido/metabolismo , Mecanorreceptores/fisiología , Datos de Secuencia Molecular , Neuronas Motoras/ultraestructura , Mutación/fisiología , Neuronas/metabolismo , Sinapsis/ultraestructura , Vesículas Sinápticas/ultraestructura , Temperatura