RESUMEN
To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule with an activating mutation. Embryonic fibroblasts proliferate normally in the absence of Cdk4 but have a delayed S phase on re-entry into the cell cycle. Moreover, mice devoid of Cdk4 are viable, but small in size and infertile. These mice also develop insulin-deficient diabetes due to a reduction in beta-islet pancreatic cells. In contrast, mice expressing a mutant Cdk4 that cannot bind the cell-cycle inhibitor P16INK4a display pancreatic hyperplasia due to abnormal proliferation of beta-islet cells. These results establish Cdk4 as an essential regulator of specific cell types.
Asunto(s)
Quinasas Ciclina-Dependientes/genética , Diabetes Mellitus/genética , Insulina/deficiencia , Islotes Pancreáticos/patología , Proteínas Proto-Oncogénicas , Animales , Línea Celular , Quinasa 4 Dependiente de la Ciclina , Quinasas Ciclina-Dependientes/metabolismo , Diabetes Mellitus/enzimología , Diabetes Mellitus/metabolismo , Activación Enzimática , Femenino , Regulación de la Expresión Génica , Hiperplasia , Infertilidad Femenina/genética , Infertilidad Masculina/genética , Islotes Pancreáticos/citología , Islotes Pancreáticos/enzimología , Masculino , Ratones , Ratones Endogámicos , Mutagénesis Sitio-Dirigida , Espermatogénesis/genéticaRESUMEN
A 4-year-old female, spayed Border Collie Dog was brought to the Veterinary Medical Teaching Hospital for evaluation of a progressive head tilt and ataxia that were unresponsive to therapy. Neurologic examination localized a right-sided lesion. The owner refused additional diagnostic tests, and necropsy was performed after euthanasia. Gross findings included atrophy of the temporal muscles and a moderately well delineated, 2.5- x 1.5- x 1.0-cm, gray soft-tissue mass compressing the right cerebellar hemisphere and dorsal hindbrain, resulting in massive dilatation of the lateral, third, and fourth ventricles and hydrocephalus. Histologic examination revealed two distinct features: undifferentiated, primitive, polygonal to fusiform cells with typical morphologic characteristics of medulloblastoma and interspersed areas containing myelinated axons and cells with glial and neuronal differentiation. Immunohistochemical examination confirmed the presence of primitive neuroepithelium and cells with glial and neuronal differentiation.
Asunto(s)
Neoplasias Cerebelosas/veterinaria , Enfermedades de los Perros/patología , Meduloblastoma/veterinaria , Animales , Astrocitos/química , Astrocitos/patología , Biomarcadores de Tumor/análisis , Transformación Celular Neoplásica , Neoplasias Cerebelosas/química , Neoplasias Cerebelosas/patología , Perros , Resultado Fatal , Femenino , Técnicas para Inmunoenzimas/veterinaria , Meduloblastoma/química , Meduloblastoma/patología , Neuronas/química , Neuronas/patologíaRESUMEN
OBJECTIVE: To examine the role of apoptosis in retinal photoreceptor degeneration in dogs with sudden acquired retinal degeneration syndrome (SARDS). SAMPLE POPULATION: Retinas from 3 dogs with SARDS and from 2 clinically normal adult dogs. PROCEDURE: Apoptosis was identified by in situ end-labeling and observation of characteristic morphologic changes by light microscopy. RESULTS: The degree of photoreceptor degeneration varied with duration of vision loss in SARDS-affected eyes. The retina of all 3 SARDS-affected eyes had numerous (34, 61, and 70) apoptotic nuclei per section that were overwhelmingly located in the outer nuclear layer. Apoptotic nuclei were not detected, or were rare in similarly sized retinal sections from normal dogs. Inflammation was not an important feature of SARDS. CONCLUSIONS: Apoptosis appears to be at least 1 mechanism of photoreceptor cell death in dogs with SARDS. CLINICAL RELEVANCE: Because apoptosis appears to be a final common pathway in many retinal degeneration syndromes, future treatment strategies that control apoptosis in other diseases may be applicable to dogs with SARDS. Halting this pathway may allow some photoreceptors to survive and, perhaps, preserve vision.
Asunto(s)
Enfermedades de los Perros , Células Fotorreceptoras/patología , Retina/patología , Degeneración Retiniana/veterinaria , Animales , Apoptosis , Perros , Femenino , Masculino , Ovariectomía , Degeneración Retiniana/patología , Degeneración Retiniana/fisiopatología , Factores de TiempoRESUMEN
Increased expression of glial fibrillary acidic protein (GFAP) is a hallmark of gliosis, the astrocytic hypertrophy that occurs during a wide variety of diseases of the central nervous system. To determine whether this increase in GFAP expression per se alters astrocyte function, we generated transgenic mice that carry copies of the human GFAP gene driven by its own promoter. Astrocytes of these mice are hypertrophic, up-regulate small heat-shock proteins, and contain inclusion bodies identical histologically and antigenically to the Rosenthal fibers of Alexander's disease. Mice in the highest expressing lines die by the second postnatal week. The results support the notion that Alexander's disease is a disorder of astrocytes, and provide an animal model for studying the causes and consequences of inclusion body disease.
Asunto(s)
Astrocitos/patología , Encefalopatías/patología , Proteína Ácida Fibrilar de la Glía/genética , Proteínas de Choque Térmico , Cuerpos de Inclusión/patología , Ratones Transgénicos/genética , Animales , Astrocitos/metabolismo , Cristalinas/genética , Cristalinas/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteínas de Choque Térmico HSP27 , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Hipertrofia , Ratones , Chaperonas Moleculares , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , ARN Mensajero/metabolismoRESUMEN
Primitive neuroectodermal tumors are composed of primitive neuroepithelial cells and include tumors of the central and peripheral nervous system. Neuroblastoma, medulloblastoma and retinoblastoma are examples of these rare malignant tumors that usually occur in young patients. This report describes a peripheral neuroblastoma in a 2 year old Boxer that presented with signs of renal disease and a palpable abdominal mass. The purpose of this paper is to describe the clinical presentation, imaging and immunohistological studies of this abdominal tumor in a young dog and to review the literature.
Asunto(s)
Neoplasias Abdominales/veterinaria , Enfermedades de los Perros/diagnóstico , Neuroblastoma/veterinaria , Neoplasias Abdominales/química , Neoplasias Abdominales/diagnóstico por imagen , Neoplasias Abdominales/patología , Animales , Biopsia , Cromogranina A , Cromograninas/análisis , Enfermedades de los Perros/diagnóstico por imagen , Perros , Inmunohistoquímica , Riñón/patología , Masculino , Neuroblastoma/química , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/patología , Sinaptofisina/análisis , Ultrasonografía , Vimentina/análisisRESUMEN
Glial fibrillary acidic protein (GFAP) is a member of the family of intermediate filament structural proteins and is found predominantly in astrocytes of the central nervous system (CNS). To assess the function of GFAP, we created GFAP-null mice using gene targeting in embryonic stem cells. The GFAP-null mice have normal development and fertility, and show no gross alterations in behavior or CNS morphology. Astrocytes are present in the CNS of the mutant mice, but contain a severely reduced number of intermediate filaments. Since astrocyte processes contact synapses and may modulate synaptic function, we examined whether the GFAP-null mice were altered in long-term potentiation in the CA1 region of the hippocampus. The GFAP-null mice displayed enhanced long-term potentiation of both population spike amplitude and excitatory post-synaptic potential slope compared to control mice. These data suggest that GFAP is important for astrocyte-neuronal interactions, and that astrocyte processes play a vital role in modulating synaptic efficacy in the CNS. These mice therefore represent a direct demonstration that a primary defect in astrocytes influences neuronal physiology.
Asunto(s)
Proteína Ácida Fibrilar de la Glía/genética , Hipocampo/fisiología , Neuronas/fisiología , Animales , Astrocitos/ultraestructura , Hipocampo/citología , Hipocampo/ultraestructura , Homocigoto , Potenciación a Largo Plazo , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica , Neuronas/ultraestructura , Células de Schwann/ultraestructura , Eliminación de Secuencia , Transmisión SinápticaRESUMEN
Transgenic pigs were created that harboured a phosphoenolpyruvate carboxykinase-bovine growth hormone construct (PEPCK-bGH). Four founder animals and two transgenic offspring from one line were evaluated between 6 1/2 and 12 months of age. There was no evidence of severe hepatic or renal lesions in these pigs, which characterised transgenic PEPCK-bGH mice previously described. While glomerular and tubular lesions in kidney sections were not identified in the transgenic pigs, mesangial cell proliferation was observed in two transgenic offspring from a single line. Additionally, glomerular size was significantly increased in four of four puberal transgenic swine when compared to age- and sex-matched controls (28.30 +/- 4.1 vs. 14.2 +/- 2.7 x 10(5) microns 3; representing 3 transgenic lines, p < 0.05). Surprisingly, no mature adipocytes were observed in subcutaneous sections obtained in transgenic GH pigs. Histological evaluation of these transgenic pigs further illustrates the requirement for precise control of growth-related genes and their protein products.
Asunto(s)
Tejido Adiposo/patología , Regulación del Desarrollo de la Expresión Génica , Hormona del Crecimiento/genética , Riñón/patología , Hígado/patología , Adipocitos/patología , Animales , Animales Modificados Genéticamente , Bovinos , Femenino , Hormona del Crecimiento/sangre , Masculino , Ratones , Fosfoenolpiruvato Carboxiquinasa (GTP)/genética , Ratas , Proteínas Recombinantes de Fusión/genética , Piel/patología , PorcinosRESUMEN
This report focuses on the diagnostic laboratory and necropsy findings in 4 llamas with adenovirus-associated hepatitis or pneumonia. In the 2 young llamas, clinical illness was characterized by chronic respiratory tract disease. In the 2 adult llamas, clinical illness was characterized by neurologic signs and a history of respiratory tract disease. Histologic examination, electron microscopy, virus isolation, and fluorescent antibody results indicated that adenovirus infection was associated with disease in all 4 llamas.
Asunto(s)
Infecciones por Adenoviridae/veterinaria , Camélidos del Nuevo Mundo , Hepatitis Viral Animal/patología , Neumonía Viral/veterinaria , Adenoviridae/aislamiento & purificación , Adenoviridae/ultraestructura , Infecciones por Adenoviridae/patología , Animales , Femenino , Hígado/microbiología , Hígado/patología , Hígado/ultraestructura , Pulmón/microbiología , Pulmón/patología , Masculino , Microscopía Electrónica , Neumonía Viral/patología , Virión/aislamiento & purificación , Virión/ultraestructuraRESUMEN
Transrectal palpation in llamas can result in iatrogenic rectal and colonic injury. The purpose of this report is to define the caudal extent of the peritoneal cavity in llamas and to describe the surgical management of rectal or colonic injuries in four llamas. Measurements were made of six adult llamas during necropsy. The mean distance from the peritoneal reflection to the anus was 3.9 +/- 0.1 cm (3.4-4.3 cm). Four llamas were examined for rectal or colonic perforations. One laceration was of partial thickness and three lacerations were of full thickness. Two of the defects were repaired by a transanal approach and two by celiotomy to facilitate removal of fecal debris and abdominal lavage. Successful repair of the rectal or colonic tears was achieved in all four llamas. Wound infection and incisional hernia occurred in both llamas that underwent celiotomy. Two llamas died 3 and 18 months later, and two llamas have survived 2 years. Rectal tears in llamas are accompanied by a high risk of peritoneal contamination, and primary closure is recommended. If fecal contamination of the abdomen has occurred, celiotomy is indicated to allow mechanical removal of fecal debris and peritoneal lavage.
Asunto(s)
Camélidos del Nuevo Mundo/lesiones , Intestino Delgado/lesiones , Recto/lesiones , Animales , Camélidos del Nuevo Mundo/cirugía , Femenino , Hernia/veterinaria , Intestino Delgado/anatomía & histología , Intestino Delgado/cirugía , Masculino , Palpación/veterinaria , Cavidad Peritoneal/anatomía & histología , Peritonitis/veterinaria , Complicaciones Posoperatorias/veterinaria , Recto/anatomía & histología , Recto/cirugía , Infección de la Herida Quirúrgica/veterinariaRESUMEN
Intestinal ischemia was induced and maintained for 60 minutes in male Sprague-Dawley rats weighing 175 to 225 g. Prior to reperfusion, the following drugs were administered via the caudal vena cava: 0.9% NaCl (0.5 ml), superoxide dismutase (SOD; 1,000 IU/kg of body weight), polyethylene glycol-conjugated SOD (PEG-SOD; 1,000 IU/kg), or the 21-aminosteroids, U74006F (3 mg/kg) or U78715G (3 mg/kg). A sham-operated control group was included. Animals from each group were euthanatized at 5 periods of reperfusion: 5 minutes, 30 minutes, 18 hours, 3 days, and 7 days after reperfusion. Fixed tissues were embedded in paraffin, sectioned at 5 microns, and stained with H&E. Villi profiled in cross section were measured from the crypt villus junction to the tip of the villus. The mean villus height for each rat was calculated and compared by two-way ANOVA to determine the effects of time and treatment. Villus height was maintained after 30 minutes of reperfusion in rats of the sham- and U74006F-treated groups; U78715G and SOD treatment attenuated the loss in villus height, and villus height was not maintained in the PEG-SOD- and 0.9% NaCl-treated rats. In all rats, villus height was comparable to, or was greater than villus height in sham-operated controls by 18 hours after reperfusion in all animals and remained constant through 7 days. Administration of the 21-aminosteroids maintained villus height after ischemia and reperfusion. Treatment with PEG-SOD did not maintain villus height to the degree observed in rats treated with SOD.