Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “mouse model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1994

Delayed-type hypersensitivity response to human papillomavirus type 16 E6 protein in a mouse model.

A mouse model incorporating the epitheliotropic nature of human papillomavirus (HPV) infections has been used to study an immune response to HPV type 16 (HPV-16) E6 protein in vivo. Using a transplantation technique, a novel immortal keratinocyte cell line expressing the E6 protein has been grafted onto syngeneic mice to re-form a differentiated epithelium overlying a granulation tissue bed. By this approach the presentation of viral antigens to the immune system can be modelled in a way analogous to the natural infection. Here we report a delayed-type hypersensitivity (DTH) reaction in grafted mice challenged intradermally with a recombinant vaccinia virus expressing the HPV-16 E6 protein. The specificity of the response was confirmed by the absence of a DTH reaction to challenge with virus expressing either HPV-16 E7 or L1 protein.

Animals↗
PubMed1992

Experimentally induced infection by oral anaerobic microorganisms in a mouse model.

A mouse model was developed to study the abscessogenic potential of pure and mixed cultures of oral anaerobes associated with infections of endodontic origin. Maximum subcutaneous lesions were seen on their backs between 3 and 14 d after inoculation. Strains of Fusobacterium nucleatum, Peptostreptococcus anaerobius, and Veillonella parvula were pathogenic in pure culture. A mixed culture of F. nucleatum with either Porphyromonas gingivalis or Prevotella intermedia was significantly more pathogenic than F. nucleatum in pure culture. Histopathological examination of tissue sections from control mice injected with India ink in the medium demonstrated a pathway of particulate migration from the backs of the mice to their abdomen.

Abdomen↗
PubMed1994

Establishment of new SCID and nude mouse models of human B leukemia/lymphoma and effective therapy of the tumors with immunotoxin and monoclonal antibody: marked difference between the SCID and nude mouse models in the antitumor efficacy of monoclonal antibody.

BALL-1, a human B leukemia/lymphoma cell line, was transplanted into nude and SCID mice under various conditions. The transplantation was substantially improved by preadaptation of BALL-1 by serial passages in newborn and young nude mice. We were able to establish the desirable conditions where 100% of SCID and nude mice that were inoculated i.p. with various doses of the adapted BALL-1 (termed BALL-1a) developed tumors. Tumors in SCID mice were disseminated to various tissues in a manner analogous to tumors in patients with B leukemia/lymphoma, whereas tumors in nude mice were not as widely disseminated and grew mainly as ascites. Flow cytometric analyses showed that all of the 11 tested cell surface markers of the parental BALL-1 were well maintained on the tumor cells recovered from the SCID and nude mice. The utility of the developed tumor models for the therapeutic studies was investigated by i.p. or i.v. administration of an anti-B leukemia/lymphoma monoclonal antibody, termed SN7 (IgG1 kappa), and SN7 immunotoxin (IT) that was prepared by conjugating SN7 to ricin A chain (RA) or deglycosylated RA (dgRA). In the nude mouse model study, SN7-RA that had been administered i.p. suppressed the tumor growth completely in all of the treated mice (n = 5) without any sign of tumor or undesirable side effects for as long as followed (i.e., 350 days), whereas unconjugated SN7 showed only a slight therapeutic effect. A control RA conjugate was not effective. In the SCID mouse model studies, several sets of experiments were carried out by i.p. or i.v. administration of IT, monoclonal antibody, or control IT. In the first three sets of experiments, SCID mice inoculated with 1.1 x 10(6) BALL-1a cells received an i.p. administration of phosphate-buffered saline or three different doses (i.e., 4 x 10 micrograms, 4 x 20 micrograms, and 4 x 30 micrograms) of therapeutic agents (SN7-RA and SN7). Virtually an identical result was obtained from the three experiments. All of the phosphate-buffered saline control group mice (n = 15) died within 35 days post tumor inoculation. In contrast, all of the mice that were treated with SN7-RA (n = 19) or with SN7 (n = 15) survived for as long as followed (i.e., 250 days). However, the unconjugated SN7 was less effective than SN7 IT for tumor suppression in SCID mice that were inoculated with a larger tumor burden (i.e., 4 x 10(7) BALL-1a cells).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Experimental dermatophytosis: the clinical and histopathologic features of a mouse model using Trichophyton quinckeanum (mouse favus).

We have established a reproducible mouse model of dermatophytosis using Trichophyton quinckeanum. There was considerable variation in the pathogenic potential among 10 different strains of T. mentagrophytes or T. quinckeanum; susceptibility to the infection varied with the inbred strain of mouse used, with BALB/c or BALB/K mice proving to be the most susceptible. The primary infection was characterized by the development of a scutulum or crust consisting of large quantities of dermatophyte mycelium, dense infiltration with neutrophils, but minimal epidermal proliferation. By contrast, a secondary infection initiated 30 days after the primary infection showed different features with early and almost total elimination of fungal elements, a predominantly mononuclear cell response, and epidermal proliferation. If the secondary infection was given at the peak of the primary illness (day 7), there was a mononuclear cell response with epidermal proliferation but fungal mycelium was prominent and not quickly eliminated. The value of this model in investigating the kinetics of the immune response to experimental dermatophytosis is discussed.

Animals↗
PubMed2005

Analysis of cholinergic markers, biogenic amines, and amino acids in the CNS of two APP overexpression mouse models.

Two transgenic mouse models expressing mutated human amyloid precursor protein and previously found to display cognitive and behavioural alterations, reminiscent of Alzheimer patients' symptomatology, were scrutinised for putative brain region-specific changes in neurochemical parameters. Brains of NSE-hAPP751m-57, APP23 and wild-type mice were microdissected to perform brain region-specific neurochemical analyses. Impairment of cholinergic transmission, the prominent neurochemical deficit in Alzheimer brain, was examined; acetylcholinesterase and choline acetyltransferase activity levels were determined as markers of the cholinergic system. Since Alzheimer neurodegeneration is not restricted to the cholinergic system, brain levels of biogenic amines and metabolites, and amino acidergic neurotransmitters and systemic amino acids were analysed as well. Cholinergic dysfunction, reflected in reduced enzymatic activity in the basal forebrain nuclei, was restricted to the APP23 model, which also exhibited more outspoken and more widespread changes in other neurotransmitter systems. Significant changes in compounds of the noradrenergic and serotonergic system were observed, as well as alterations in levels of the inhibitory neurotransmitter glycine and systemic amino acids. These observations were clearly in occurrence with the more pronounced histopathological and behavioural phenotype of the APP23 model. As transgenic models often do not represent an end-stage of the disease, some discrepancies with results from post-mortem human Alzheimer brain analyses were apparent; in particular, no significant alterations in excitatory amino acid levels were detected. Our findings of brain region-specific alterations in compound levels indicate disturbed neurotransmission pathways, and greatly add to the validity of APP23 mice as a model for Alzheimer's disease. Transgenic mouse models may be employed as a tool to study early-stage neurochemical changes, which are often not accessible in Alzheimer brain.

Acetylcholine↗
PubMed1995

Spontaneous and X-ray-induced deletion mutations in a LacZ plasmid-based transgenic mouse model.

Transgenic mouse mutation models carrying bacterial marker genes in bacteriophage lambda shuttle vectors have been applied to study spontaneous or induced mutations in vivo. However, due to the nature of the shuttle vector these models are insensitive to large deletions. Clastogenic agents, which predominantly induce large deletions, were therefore found to yield very low responses in these assays. Here we report the use of LacZ plasmid-based transgenic mice, allowing the detection of a broad spectrum of mutations. Treatment of mice with X-rays (5 x 50 rads) resulted in induction of up to about 5-fold higher mutation frequencies in lung, spleen and liver. Analysis of spontaneous and induced mutant LacZ genes indicated that at least 40-50% of all mutations were caused by deletions. The possibility of detecting a broad spectrum of mutations with this system suggests that the LacZ plasmid-based transgenic mouse may be the mammalian model of choice for studying spontaneous and induced mutations in vivo.

Animals↗
PubMedDate not supplied

Mouse models incorporating alterations in the major tumor suppressor genes P53 and P16: their use in screening for potential carcinogens, developing further relevant mouse models, and screening for potential chemopreventive and chemotherapetutic agents.

This review is primarily a follow up to an initial review on this subject that the authors published 4 years ago [Lubet et al., Exp Lung Res. 2000; 581-593]. The present review gives a brief discussion of certain background points and rationale for development of these specific models, which had been presented in greater detail in the earlier article. In that initial article the authors identified the potential use of mutant mice in screening for carcinogens as well as preventive or therapeutic agents, discussed the relevance of the dominant-negative P53 mutation, as contrasted with knockout P53 mice, and briefly discussed the pros and cons of mice with a germline mutation in tumor suppressor genes in developing mouse models. The primary objective of the present review is to describe more recent studies using mice the dominant-negative P53 mutation as well as to introduce studies with mice with a heterozygous knockout of the P16/Ink4A ARF locus.

Adenocarcinoma↗
PubMed2004

A rapid flow cytometric method for determining the cellular composition of bronchoalveolar lavage fluid cells in mouse models of asthma.

Mouse models of allergic asthma are increasingly used to study the immunopathology of this complex disorder. The degree and type of airway inflammation is often studied by determination of differential cell counts on cytospins of bronchoalveolar lavage fluid (BALF) cells stained with May-Grünwald Giemsa, in which the separation of eosinophils (eos) from neutrophils (neutro) and of monocytes (mono) from activated T cells can be quite problematic. In this study, we compared differential cell counts based on morphological criteria on May-Grünwald Giemsa stained cytospins with a newly developed flow cytometric method. BAL fluid cells were identified based on forward and side scatter characteristics (FSC and SSC), autofluorescence of macrophages, and simultaneous one-step staining with antibodies for T cells (CD3-Cy-Chrome), B cells (B220-Cy-Chrome), eosinophils (CCR3-PE), and dendritic cells (DCs) (MHCII-FITC, CD11c-APC). The validity of this flow cytometric determination was tested by morphological analysis of flow-sorted cellular subsets. In an animal model of ovalbumin-induced asthma, this new method correlated very well with the differential counts based on cytospins. Flow cytometric determination of the cellular composition of BAL fluid in mouse models of asthma is a rapid and easy method that can replace differential cell counts based on morphology.

Animals↗
PubMed1985

Virulence of human and bovine isolates of group B streptococci (types Ia and III) in experimental pregnant mouse models.

Two experimental mouse models were tested for their suitability in measuring virulence of two human and two bovine isolates (types Ia and III) of group B streptococci. In the first model, the kinetics of the number of bacteria in the spleen, liver, and placenta of mice inoculated intravenously on day 16 of pregnancy were monitored for 48 h after infection. In the second model, lethality and abortion were recorded for mice inoculated on day 13 of pregnancy. Levels of colonization in spleens or livers and lethality were significantly greater (P less than 0.001) for human isolates than for bovine isolates. In contrast, no statistically significant differences in the ability to colonize placentas and to induce abortions were noted between human and bovine isolates. The results showed that pregnant mice were more sensitive than nonpregnant mice to a challenge with group B streptococci. The results also suggest that placental colonization and abortion could be a suitable mouse model in evaluating the virulence of human and bovine isolates of group B streptococci.

Animals↗
PubMed1983

Leptospirosis and the maintenance host: a laboratory mouse model.

A laboratory mouse model was used to investigate the criteria that have been suggested as differentiating between a maintenance host and an accidental host for a particular leptospiral serovar. The comparative studies were conducted with serovars ballum, pomona, balcanica and hardjo. The relative pathological response, ratio of serological to bacteriological prevalence, level of serological response, age-susceptibility to infection and demonstration of artificial intraspecies transmission were found to be inadequate criteria with which to differentiate maintenance and accidental hosts for a particular serovar. The demonstration of natural intraspecies transmission was considered to be the definitive criterion for differentiating such hosts. In the light of the results obtained from the laboratory mouse model and the results obtained from field studies, a maintenance host may be defined as an animal which is capable of acting as a natural source of leptospiral infection for its own species. A maintenance population may be defined as a population of a species of animal which acts as a continuous reservoir of a serovar in a specific ecosystem.

Age Factors↗
PubMed2003

Spontaneous pituitary abnormalities and mammary hyperplasia in FVB/NCr mice: implications for mouse modeling.

The FVB/N mouse strain is widely used in the generation of transgenic mouse models. We have observed that mammary glands of wild-type virgin female FVB/NCr mice frequently have the morphologic and histologic appearance of a gland during pregnancy. By 13 months of age, the mammary glands of more than 40% of the mice examined had lobuloalveolar hyperplasia that was characterized by the presence of secretory alveoli and distended ducts apparently containing secretory material. The prevalence of this phenotype further increased with age. The mammary phenotype was highly correlated with the presence of proliferative, prolactin-secreting lesions in the pituitary gland. In mice aged 18 to 23 months, hyperplasia of the pars distalis was seen in 11 of 21 mice (52%), and a further 4 of 21 mice (19%) had pituitary adenomas. Pituitary hyperplasia was already evident in some mice as young as nine months. The pituitary phenotype was also associated with high prevalence (4/6 mice) of spontaneous mammary tumors in aged multiparous, but not virgin FVB/NCr mice. This high prevalence of pituitary abnormalities and their effects on the mammary gland have important consequences for the interpretation of new phenotypes generated in transgenic models using this mouse substrain.

Animals↗
PubMed2004

Males lose hearing earlier in mouse models of late-onset age-related hearing loss; females lose hearing earlier in mouse models of early-onset hearing loss.

Gender-related differences in human hearing have been attributed to genetic, environmental, and/or genetic x environmental interactive factors. These differences tend to increase with age, with males showing greater high frequency threshold elevations. An appropriate animal model could aid in prediction, treatment, and prevention of some of these losses. This paper examines inbred strains of mice that are widely used as models of late- (CBA/J and CBA/CaJ) and early- (C57BL/6J) onset age-related hearing loss. In the former two genotypes, the thresholds to high frequency stimuli of the auditory brainstem response (ABR) are higher in the male than in the female. This gender difference was less pronounced in thresholds to the cochlear nerve envelope response of the CBA/CaJ, although this response was more sensitive to the influence of age than was the ABR. In contrast, the male C57BL/6J had more sensitive thresholds than the female, with both measures showing massive loss of sensitivity with increasing age. The data are discussed in terms of the applicability of these animals as tools for examining factors that degrade cochlear function.

Aging↗
PubMed2001

Mitochondrial alterations caused by defective peroxisomal biogenesis in a mouse model for Zellweger syndrome (PEX5 knockout mouse).

Zellweger syndrome (cerebro-hepato-renal syndrome) is the most severe form of the peroxisomal biogenesis disorders leading to early death of the affected children. To study the pathogenetic mechanisms causing organ dysfunctions in Zellweger syndrome, we have recently developed a knockout-mouse model by disrupting the PEX5 gene, encoding the targeting receptor for most peroxisomal matrix proteins (M Baes, P Gressens, E Baumgart, P Carmeliet, M Casteels, M Fransen, P Evrard, D Fahimi, PE Declercq, D Collen, PP van Veldhoven, GP Mannaerts: A mouse model for Zellweger syndrome. Nat Genet 1997, 17:49-57). In this study, we present evidence that the absence of functional peroxisomes, causing a general defect in peroxisomal metabolism, leads to proliferation of pleomorphic mitochondria with severe alterations of the mitochondrial ultrastructure, changes in the expression and activities of mitochondrial respiratory chain complexes, and an increase in the heterogeneity of the mitochondrial compartment in various organs and specific cell types (eg, liver, proximal tubules of the kidney, adrenal cortex, heart, skeletal and smooth muscle cells, neutrophils). The changes of mitochondrial respiratory chain enzymes are accompanied by a marked increase of mitochondrial manganese-superoxide dismutase, as revealed by in situ hybridization and immunocytochemistry, suggesting increased production of reactive oxygen species in altered mitochondria. This increased oxidative stress induced probably by defective peroxisomal antioxidant mechanisms combined with accumulation of lipid intermediates of peroxisomal beta-oxidation system could contribute significantly to the pathogenesis of multiple organ dysfunctions in Zellweger syndrome.

Adenosine Triphosphate↗
PubMed2006

Diabetic atherosclerosis mouse models.

Coronary heart disease (CHD) due to atherosclerosis is the leading cause of death in the USA, and accelerated CHD has emerged as a leading cause of morbidity and mortality in diabetic patients in the USA and worldwide. This has highlighted the importance and urgency of studying the mechanism of diabetic atherosclerosis and exploring therapeutic options. Due to its unique advantages over other animal models, the mouse is the most used model for studying the mechanism of diabetes-accelerated atherosclerosis and exploring effective therapeutic approaches. In the past decade, several diabetic atherosclerosis mouse models have been established. Currently, however, there is no ideal animal model for diabetic atherosclerosis. To determine the characteristics of the models that more closely resemble human diabetic atherosclerosis disease, this review focuses on the common diabetic atherosclerosis mouse models with respect to the following issues: (1) whether the mice retain diabetic condition; (2) whether the diabetes accelerates atherosclerosis or increases atherogenic inflammation; (3) whether these factors respond to medical interventions. The discussion is aimed at identifying different diabetic mouse models and their features, in order to heighten awareness of the appropriate models that may provide useful tools for studying the mechanism of diabetes-accelerated atherosclerosis and evaluating therapeutic options.

Aldehyde Reductase↗
PubMed2003

[Establishment of a mouse model of cyclophosphamide-induced thrombocytopenia and determination of platelet function in this model].

OBJECTIVE: To establish a mouse model of acute hematopoietic failure and explore the pathological basis of platelet changes in bone marrow suppression. METHODS: An initial large dose of cyclophosphamide (200 mg/kg) was injected through the tail veins of the mice, follow by daily intraperitoneal injection starting on the next day for 7 d. The number and morphology of the cells in the peripheral blood and bone marrow were observed by means of cell counting and smear, respectively, with the platelet aggregation determined using ADP. The coagulation time was measure by turbidimetry. RESULTS: The amount of platelets, erythrocytes, leukocytes and the nucleated cells in mice bone marrow was significantly lowered in the mouse models in comparison with the control mice, and the normal hematopoietic tissues were depressed. The blood platelets in the models were lowered by 49%, an amplitude of declination significantly greater than that occurring in the erythrocytes and leukocytes (by 28% and 25% respectively). Though the mean platelet volume and percent platelet aggregation underwent no obvious changes, the coagulation time was significantly shortened. CONCLUSION: The methods we described for establishing mouse models of hematopoietic failure induced by cyclophosphamide is rapid and highly efficient, and may facilitate ready preparation of mouse models of thrombocytopenia which respond strongly to cyclophosphamide without blood platelets function impairment.

Animals↗
PubMed2004

Do mouse models of allergic asthma mimic clinical disease?

Experimental mouse models of allergic asthma established almost 10 years ago offered new opportunities to study disease pathogenesis and to develop new therapeutics. These models focused on the factors governing the allergic immune response, on modeling clinical behavior of allergic asthma, and led to insights into pulmonary pathophysiology. Although mouse models rarely completely reproduce all the features of human disease, after sensitization and respiratory tract challenges with antigen, wild-type mice develop a clinical syndrome that closely resembles allergic asthma, characterized by eosinophilic lung inflammation, airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and eventually, airway remodeling. There are, however, differences between mouse and human physiology that threaten to limit the value of mouse models. Three examples of such differences relate to both clinical manifestations of disease and underlying pathogenesis. First, in contrast to patients who have increased methacholine-induced AHR even when they are symptom-free, mice exhibit only transient methacholine-induced AHR following allergen exposure. Second, chronic allergen exposure in patients leads to chronic allergic asthma, whereas repeated exposures in sensitized mice causes suppression of disease. Third, IgE and mast cells, in humans, mediate early- and late-phase allergic responses, though both are unnecessary for the generation of allergic asthma in mice. Taken together, these observations suggest that mouse models of allergic asthma are not exact replicas of human disease and thus, question the validity of these models. However, observations from mouse models of allergic asthma support many existing paradigms, although some novel discoveries in mice have yet to be verified in patients. This review presents an overview of the clinical aspects of disease in mouse models of allergic asthma emphasizing (1). the factors influencing the pathophysiological responses during the initiation and perpetuation of disease, (2). the utility of mouse models for studying clinical manifestations of disease, and (3). the applicability of mouse models for testing new treatments for allergic asthma.

Allergens↗