DigitalUM :: Browsing by Subject "Animal model"

Browsing by Subject "Animal model"

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Open Access
Animal in vivo models of EBV-associated lymphoproliferative diseases: Special references to rabbit models
(Murcia : F. Hernández, 2002) Hayashi, K.; Teramoto, N.; Akagi, T.
Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-associated diseases. Here we review those previous models using EBV or EBV-like herpesviruses and describe the details on our two newly-developed rabbit models of lymphoproliferative diseases (LPD) induced by simian EBV-like viruses. The first is Cynomolgus- EBV-induced T-cell lymphomas in rabbits inoculated intravenously (77- 90%) and orally (82- 89%) during 2 - 5 months. EBV-DNA was detected in peripheral blood by PCR from 2 days after oral inoculation, while anti- EBV-VCA IgG was raised 3 weeks later. Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphoma cell lines, most of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The second is the first animal model for EBV-infected T-cell LPD with virus-associated hemophagocytic syndrome (VAHS), using rabbits infected with an EBV-like herpesvirus, Herpesvirus papio (HVP). Rabbits inoculated intravenously with HVP-producing cells showed increased anti-EBV-VCAIgG titers, and most (85%) subsequently died of fatal LPD and VAHS, with bleeding and hepatosplenomegaly, during 22-105 days. Peroral spray of cell-free HVP induced viral infection with seroconversion in 3 out of 5 rabbits, with 2 of the 3 infected rabbits dying of LPD with VAHS. Atypical T lymphocytes containing HVPDNA and expressing EBER-1 were observed in many organs. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. These rabbit models are also useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens.
Open Access
Animal models for disc degeneration-an update
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Jin, Li; Balian, Gary; Li, Xudong Joshua
Intervertebral disc degeneration is considered a major cause of back pain that places a heavy burden on society, both because of its effect on the physiology of individuals and its consequences on the world economy. During the past few decades, research findings in the pre-clinical setting have led to a significant increase in the understanding of intervertebral disc degeneration, although many aspects of the disease remain unclear. The goal of this review is to summarize existing animal models for disc degeneration studies and the difficulties that are associated with the use of such models. A firm understanding of the cellular and molecular events that ensue as a result of injuries, as well as environmental factors, could be instrumental in the development of targeted therapies for the treatment of intervertebral disc degeneration
Open Access
Consumption of commonly used artificial food dyes increases activity and oxidative stress in the animal model Caenorhabditis elegans
(Elsevier, 2023-05-02) Guerrero Rubio, M. Alejandra; Hernández García, Samanta; García-Carmona, Francisco; Gandía Herrero, Fernando; Bioquímica y Biología Molecular A
In recent decades, the consumption of artificial colorants in foods and beverages has increased despite of concerns in the general population raised by studies that have shown possible injurious effects. In this study, tartrazine, sunset yellow, quinoline yellow, ponceau 4R, carmoisine and allura red were employed as pure compounds to explore their effects in vivo in the animal model Caenorhabditis elegans. The exposition of C. elegans to these artificial dyes produced damage related with aging such as oxidative stress and lipofuscin accumulation, as well as a heavy shortening of lifespan, alterations in movement patterns and alterations in the production of dopamine receptors. Besides, microarray analysis performed with worms treated with tartrazine and ponceau 4R showed how the consumption of synthetic colorants is able to alter the expression of genes involved in resistance to oxidative stress and neurodegeneration.
Open Access
Cooperative role between p21cip1/waf1 and p27kip1 in premature senescence in glandular proliferative lesions in mice
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) García-Fernández, R.A.; García-Palencia, P.; Suárez, C.; Sánchez, M.A.; Gil-Gómez, G.; Sánchez, B.; Rollán, E.; Martín-Caballero, J.; Flores, J.M.
Cellular senescence has been considered a novel target for cancer therapy. It has also been pointed out that p21cip1/waf1 and p27kip1 cyclin-dependent kinase inhibitors (CKIs) play a role in cellular senescence in some tumor types. Therefore, in order to address the possibility of a cooperative role between p21 and p27 proteins in senescence in vivo we analyzed cellular senescence in spontaneous glandular proliferative lesions (adrenal, thyroid and pituitary glands) in a double-KO mice model, using γH2AX, p53, p16, PTEN and Ki67 as senescence markers. The results obtained showed that p21p27 double-null mice had the lowest number of γH2AX positive cells in glandular hyperplasias and benign tumors. Also, in this group, Ki67 proliferation index correlated with a lower immunohistochemical expression of γH2AX and p53. The expression of p16 and PTEN do not seem to cause synergism of senescence in the benign lesions analyzed in p21p27 double-KO mice. These observations suggest an intrinsic cooperation between p21 and p27 CKIs in the activation of stress-induced cellular senescence and tumor progression in vivo, which would be a physiological mechanism to prevent tumor cell proliferation.
Open Access
Critical and diverse in vivo roles of apoptosis signal-regulating kinase 1 in animal models of atherosclerosis and cholestatic liver injury
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Yamada, Sohsuke; Noguchi, Hirotsugu; Tanimoto, Akihide
. Apoptosis plays pivotal in vivo roles in not only vital processes, such as cell turnover and embryonic development, but also various inflammatory disorders. However, the role of apoptosis by vascular and hepatic cells in the respective progression of atherosclerosis and liver injury remains controversial. Apoptosis signalregulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase family member that is activated through distinct mechanisms in response to various cytotoxic stressors. ASK1, ubiquitously expressed, is situated in an important upstream position for many signal transduction pathways, which subsequently induce inflammation and/or apoptosis. Our serial in vivo studies have uniquely reported that the expression of phosphorylated ASK1 is variably seen in atherosclerotic lesions or bile-duct-ligation (BDL)- induced injury livers. In mice genetically deficient of ASK1 (ASK1-/- ), activated ASK1 signaling accelerates high-cholesterol-diet-induced necrotic lipid core formation by inducing macrophage apoptosis and enhances ligation injury-induced vascular remodeling via pro-inflammatory reactions and by stimulating apoptosis of smooth muscle cells. In contrast, in models of BDL-induced cholestatic liver injury, the pathogenic roles of ASK1-mediated early necro-inflammation, but not apoptosis, and the proliferation of hepatocytes and cholangiocytes are crucial in subsequent peribiliary fibrosis/fibrogenesis. These animal models of acute to chronic inflammatory diseases show that stimulated ASK1 signaling critically and diversely regulates not only hypercholesterolemia-induced atherosclerosis and injury-induced arteriosclerosis, but also the acute and subacute-to-chronic phase of BDL-induced cholestasis. We herein review the diverse, key in vivo roles of ASK1 signaling in the pathogenesis of inflammatory disorders closely related to metabolic syndrome.
Open Access
Development of germ cell neoplasia in situ in chinchilla rabbits
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Vigueras-Villaseñor, Rosa María; Montelongo Solís, Paola; Chávez-Saldaña, Margarita; Gutiérrez-Pérez, Oscar; Cortés Trujillo, Lucero; Rojas-Castañeda, Julio César
The present study was designed to describe the development of germ cell neoplasia in situ in Chinchilla rabbit by administration of estradiol. The study was performed in rabbits distributed into two groups: control and 17 β-estradiol. The determination of histological alterations and POU5F1 and c-kit proteins employed as biomarkers for the diagnosis of this neoplasia was carried out. Testicular descent and complete spermatogenesis were observed in the control group. The protein biomarkers were negative. However, in the rabbits treated with estradiol, the testes remained undescended with the gonocytes undifferentiated to spermatogonia. There were histological lesions owing to germ cell neoplasia in situ and positive to POU5F1 and c-kit proteins. These findings indicate that the chinchilla rabbit is an ideal model to study this neoplasia in which the histological characteristics and biomarkers of the disease could be clearly observed. Using this model we suggested that the persisting gonocytes could be responsible for the development of germ cell neoplasia in situ.
Open Access
Epithelial mesenchymal transition in the progression of renal disease in dogs
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Benali, S.L.; Lees, G.E.; Castagnaro, M.; Aresu, L.
Chronic kidney disease (CKD) in dogs is the final common pathway resulting from persistent renal injury and is characterized by progressive tubulointerstitial damage (TID). Pathogenesis of CKD is divided into an initial inflammatory phase with a predominantly mononuclear infiltrate followed by a fibrotic phase with increased numbers of fibroblasts and extracellular matrix deposition that causes a progressive reduction of functional parenchyma. Proteinuria is a common manifestation of renal diseases in dogs, and its role in the pathogenesis of CKD is still uncertain. Nevertheless, the degree of proteinuria in dogs correlates with TID progression. Increased protein filtration may have direct effects on tubular epithelial cells (TECs) that induce them to express the major histocompatibility complex type II, and thereby contribute to lymphocyte recruitment. Thus, an active pro-inflammatory role is proposed for TECs in TID progression. Moreover TECs are believed to actively participate in the mechanisms of renal fibrosis. Epithelial-Mesenchymal-Transition (EMT) of TECs in canine TID has been studied in the last decade. Downregulation of adhesion molecules and loss of epithelial markers in TECs directly correlate with the severity of TID and with de novo expression of mesenchymal markers. Tubular basement membrane (TBM) disruption is an early EMT event. Increased activity of Matrix Metalloproteinase-2 and its co-localization with TBM splitting suggests an active role for the enzyme in inducing EMT. Processes occurring in canine CKD share many similarities with its human counterpart, making the dog a good model in which to examine the mechanisms of TID progression.
Open Access
Histological complexities of pancreatic lesions from transgenic mouse models are consistent with biological and morphological heterogeneity of human pancreatic cancer
(Murcia : F. Hernández, 2007) Liao, J.D.; Adsay, N.V.; Khannani, F.; Grignon, D.; Thakur, A.; Sarkar, F.H.
Although pancreatic cancer is the fourth leading cause of cancer death, it has received much less attention compared to other malignancies. There are several transgenic animal models available for studies of pancreatic carcinogenesis, but most of them do not recapitulate, histologically, human pancratic cancer. Here we review some detailed molecular complexity of human pancreatic cancer and their reflection in histomorphological complexities of pancreatic lesions developed in various transgenic mouse models with a special concern for studying the effects of chemotherapeutic and chemopreventive agents. These studies usually require a large number of animals that are at the same age and gender and should be either homozygote or heterozygote but not a mixture of both. Only single-transgene models can meet these special requirements, but many currently available models require a mouse to simultaneously bear several transgene alleles. Thus it is imperative to identify new gene promoters or enhancers that are specific for the ductal cells of the pancreas and are highly active in vivo so as to establish new single-transgene models that yield pancreatic ductal adenocarcinomas for chemotherapeutic and chemopreventive studies
Open Access
The morphological changes of exocrine pancreas in chronic pancreatitis
(Murcia : F. Hernández, 1999) Ashizawa, N.; Niigaki, M.; Hamamoto, N.; Kaji, T.; Katsube, T.; Sato, S.; Endoh, H.; Hidaka, K.; Watanabe, M.; Kinoshita, Y.
The following changes were found by either light or electron microscopic observation of the pancreas in spontaneously developed chronic pancreatitis models (WBNIKob rats, spontaneously hypertensive rats, and rats with common bile-pancreatic duct stones) and in experimental models of chronic pancreatitis (alcoholic pancreatitis, ischemic pancreatitis, and obstructive pancreatitis): 1) the units of lobules, which were constituted by acinar cell deletion, ductular proliferation, and fibrosis; and 2) tortuous or helical ductal channels of pancreatic ducts with periductal fibrosis, which had many crater-like depressions and very long cilia in their inner surface. These are considered to be the results of obstructive pancreatitis, which are caused by the reactions of defensive factors against the increase of pancreatic duct pressure, including the apoptosis of acinar cells, the hyperplasia and hypertrophy of duct cells, a tighter junctional complex of duct cells, and periductal fibrosis.
Open Access
Protective effects of the pericellular matrix of chondrocyte on articular cartilage against the development of osteoarthritis
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Liu, Chenlu; Wang, Beiyu; Xiao, Li; Li, Yefu; Xu, Lin; Zhao, Zhihe; Zhang, Lin
Understanding the pathogenesis of osteoarthritis (OA) provides invaluable information in the search of therapeutic targets for the development of disease-modifying OA drugs. Emerging results from investigations demonstrate that the pericellular matrix of chondrocytes plays important roles in protecting articular cartilages from being degraded. Thus, maintaining the structural integrity of the pericellular matrix may be an effective approach to prevent the development of osteoarthritic joints. In this review article, we discuss the consequences of lacking one or more components of the pericellular matrix, and biological effects of the destruction of the pericellular matrix in the development of OA. We believe that more attention should be directed towards the pericellular matrix for the identification of novel biomarkers and therapeutic targets for the prevention and treatment of OA.
Open Access
Von Hippel-Lindau Disease (VHL): A need for a murine model with retinal hemangioblastoma
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Park, Stanley; Chan, Chi-Chao
Von Hippel-Lindau (VHL) disease is a highly penetrant autosomal dominant systemic malignancy that gives rise to cystic and highly vascularized tumors in a constellation of organs. Patients with VHL disease commonly present with hemangioblastomas in the central nervous system and the eye while other manifestations include pheochromocytoma, clear cell renal cell carcinoma, endolymphatic sac tumors of the middle ear, pancreatic cystadenomas, epididymal and broad ligament cystadenomas. Animal models inactivating the VHL gene product in various organ tissues have been constructed over the past 15 years to parse its HIF-associated mechanisms and its link to tumorigenesis. These models, despite advancing our understanding the molecular role of VHL, are by and large unable to recapitulate the more common features of human VHL disease. Up to date, no model exists that develop retinal hemangioblastomas, the most common clinical manifestation. The purpose of this review is: (1) to discuss the need for an ocular VHL model, (2) to review the animal models that recapitulate clinical VHL disease and (3) to propose potential mechanisms of tumorigenesis for the development of ocular VHL

Browsing by Subject "Animal model"

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