SEARCH · Search PubMed

Results for “Mouse models”

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.

SourceResearch connectionFrom yearThrough year

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

At least 379 records · Page 21Linked to original sources

PubMed2005

Trehalose reduces aggregate formation and delays pathology in a transgenic mouse model of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that presents in the fifth or sixth decade with dysphagia, ptosis and proximal limb weakness. OPMD is caused by the abnormal expansion of a polyalanine tract within the coding region of polyA binding protein nuclear 1 (PABPN1). The resultant mutant PABPN1 forms aggregates within the nuclei of skeletal muscle fibres. We have previously described a transgenic mouse model of OPMD that recapitulates the human disease and develops progressive muscle weakness accompanied by the formation of aggregates in skeletal muscle nuclei. The chemical chaperone trehalose has been used effectively to alleviate symptoms in a mouse model of Huntington's disease and is thought to elicit its effect by binding and stabilizing partially folded polyglutamine proteins and inhibiting the formation of aggregates. Here, we show that trehalose reduces aggregate formation and toxicity of mutant PABPN1 in cell models. Furthermore, oral administration of trehalose attenuated muscle weakness, reduced aggregate formation and decreased the number of TUNEL-labelled nuclei in skeletal muscle in an OPMD transgenic mouse model. Thus, anti-aggregation therapy may prove effective in the treatment of human OPMD.

Analysis of Variance↗

PubMed2004

An ALS mouse model with a permeable blood-brain barrier benefits from systemic cyclosporine A treatment.

To test potentially beneficial drugs to amyotrophic lateral sclerosis (ALS), we created an ALS mouse model with a permeable blood-brain barrier, by crossing the G93A-SOD1 transgenic mouse with a multiple drug resistance type 1a/b (mdr1a/b) gene knockout mouse. To validate the model, we administered cyclosporine A intraperitoneally to the mice. Cyclosporine A accumulated in the brain and spinal cord of this mouse model, whereas it was unable to penetrate the CNS of mdr1a/b wild-type animals. Systemic administration of cyclosporine A extended the life of the double-mutant male mice by approximately 12%. Surprisingly, the effect was more robust in male mice and only marginal in female mice. These results demonstrate the usefulness of this combined mouse model for the testing of potentially therapeutic drugs and support the role of mitochondrial-mediated apoptosis in the pathway to motor neuron death in SOD1-associated ALS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

[A modified mouse model of oxygen-induced retinopathy].

PURPOSE: To set up a simple and effective oxygen-induced retinopathy (OIR) mouse model. METHODS: Eyes from P17 mice in modified OIR group(Group A)and traditional OIR group (Group B) were snap frozen for immunohistochemical analysis with antibodies against GSL Flat-mounted, fluorescein-conjugated dextran-perfused retinas were examined to assess the retinal vasculature. The mortality of nursing mothers, survival rate of modeling mice and neovascularization ratio in Group A were obtained and compared with those in Group B. RESULTS: Loss of the central retinal vasculature and the neovascular tufts were observed in GSL retinal immunohistochemical analysis. A vascular area and neovasculature area were significantly larger and more typical in Group A than those in Group B. A lower mortality of nursing mothers, higher survival rate and neovascularization ratio of modeling mice was achieved in Group A. CONCLUSIONS: This modified oxygen-induced retinopathy mouse model is a simple, effective method, with more typical neovasculature were obtained.

Animals↗

PubMed2004

Genetic background markedly influences vulnerability of the hippocampal neuronal organization in the "twitcher" mouse model of globoid cell leukodystrophy.

The twitcher mouse is well known as a naturally occurring authentic mouse model of human globoid cell leukodystrophy (GLD; Krabbe disease) due to genetic deficiency of lysosomal galactosylceramidase. The twitcher mice used most commonly are on the C57BL/6J background. We generated twitcher mice that were on the mixed background of C57BL/6J and 129SvEv, the standard strain for production of targeted mutations. Twitcher mice on the mixed background were smaller and had a shorter lifespan than were those on the C57BL/6J background. Many twitcher mice on the mixed background developed generalized seizures around 30 days that were never seen in twitcher mice on the C57BL/6J background. Neuropathologically, although the degree of the typical demyelination with infiltration of macrophages was similar in the central and peripheral nervous systems, in both strains, marked neuronal cell death was observed only in twitcher mice on the mixed background. In the hippocampus, the neuronal cell death occurred prominently in the CA3 region in contrast to the relatively well-preserved CA1 and CA2 areas. This neuropathology has never been seen in twitcher mice on the C57BL/6J background. Biochemically, the brain of twitcher mice on the mixed background showed much greater accumulation of lactosylceramide. Genetic background must be carefully taken into consideration when phenotype of mutant mice is evaluated, particularly because most targeted mutants are initially on a mixed genetic background and gradually moved to a pure background. These findings also suggest an intriguing possibility of important function of some sphingolipids in the hippocampal neuronal organization and maintenance.

Animals↗

PubMed1998

Histochemical and molecular analyses of distraction osteogenesis in a mouse model.

A tibial lengthening scheme in the mouse was used to study the molecular and cellular events regulating tissue regeneration during distraction osteogenesis. Here, we report on the surgical technique and frame design and describe the histochemical and molecular aspects of distraction during different phases of treatment. A total of 26 mice were used in this study. The treatment protocol was divided into a latency period of 7 days, a phase of active distraction that lasted 10 days with a distraction rate of 0.42 mm/day, and a maturation phase of 9 days. During latency, the distraction site resembled a stabilized fracture callus on both a histochemical and a molecular level. During active distraction, the gap was characterized by a central fibrous interzone bordered by primary matrix fronts, regenerate bone aligned with the distraction force, parallel columns of vascular sinusoids, and a medullary cavity. Alkaline phosphatase activity was detected in the endosteal and periosteal surfaces of the bone ends. Tartrate resistant acid phosphatase staining revealed that osteoclasts remodeled the bone regenerate as it formed. Collagen type I was expressed in the periosteum and the primary matrix front during distraction, whereas collagen type-II transcripts were localized to discrete regions on the periosteal surfaces, immediately adjacent to the osteotomy ends. Collagen type-II transcripts were not detected in the fibrous interzone. During the maturation phase, cells within the fibrous interzone expressed collagen type I and exhibited abundant alkaline phosphatase activity, suggesting that they had begun to terminally differentiate. Collectively, these data demonstrate the utility of a mouse model to study the molecular and cellular bases for the regeneration and remodeling of tissue.

Acid Phosphatase↗

PubMed2000

Mouse models of focal arterial and venous thrombosis.

Mouse models of arterial and venous thrombosis have gained increasing interest over the last 15 years, due to direct availability of a growing number of genetically modified mice, improved technical feasibility, standardization of new models of local thrombosis, and low maintenance costs. In order to provide an overview of suitable models for the study of arterial and venous thrombosis in mice, we have systematically searched MEDLINE electronic databases for publications reporting on murine thrombo-embolic models from 1966-1999. We found that the variety of murine thromboembolic models through 1995 was rather limited, as most methods used intravenous injections of strong coagulation triggers such as thrombin, thromboplastin and collagen, causing lethal thromboembolism. Between 1996 and the end of 1999, a number of more sophisticated murine models of local acute or chronic thrombosis have been established. They seem to be more suitable for mimicking the natural scenario of thrombosis and, therefore, are preferable models for pathophysiological or drug evaluation studies. In this paper various models are described and their advantages and limitations discussed.

Animals↗

PubMed2001

Mouse models of cystic fibrosis.

The development of mouse models for cystic fibrosis has provided the opportunity to dissect disease pathogenesis, correlate genotype and phenotype, study disease-modifying genes and develop novel therapeutics. This review discusses the successes and the challenges encountered in characterizing and optimizing these models.

Animals↗

PubMed1997

Impaired Ca-signaling in astrocytes from the Ts16 mouse model of Down syndrome.

The trisomy 16 mouse model of Down syndrome has been used to compare calcium (Ca)-homeostasis and Ca-signaling in astrocytes from trisomic mice and from diploid littermates. Ratio calcium-imaging of Fura-2/AM loaded primary astroglial cultures prepared from the hippocampus shows that resting Ca levels are on average significantly higher in trisomic than in the control astrocytes (280 vs. 120 nM). Serotonin (3 microM) and glutamate (30-300 microM) evoked transient Ca-increases from 400 to 600 nM in euploid but from only 20 to 150 nM in trisomic astrocytes. Imaging of ATP-driven Ca-accumulation in cellular organelles revealed a significantly stronger uptake of Ca in trisomic astrocytes that might buffer cytosolic Ca-increases. Our results demonstrate major disturbances in Ca-signaling in trisomic astrocytes that are likely to be of pathophysiological relevance.

Adenosine Triphosphate↗

PubMed2006

Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse model.

When given orally to a transgenic mouse model of Alzheimer disease, cyclohexanehexol stereoisomers inhibit aggregation of amyloid beta peptide (Abeta) into high-molecular-weight oligomers in the brain and ameliorate several Alzheimer disease-like phenotypes in these mice, including impaired cognition, altered synaptic physiology, cerebral Abeta pathology and accelerated mortality. These therapeutic effects, which occur regardless of whether the compounds are given before or well after the onset of the Alzheimer disease-like phenotype, support the idea that the accumulation of Abeta oligomers has a central role in the pathogenesis of Alzheimer disease.

Alzheimer Disease↗

PubMed2000

Mouse models of C. pneumoniae infection and atherosclerosis.

Mouse models were used to determine whether Chlamydia pneumoniae establishes chronic infection of the aorta and contributes to atherogenesis. Persistent infection of the aorta occurred in 11 of 31 hyperlipidemic apolipoprotein E-deficient (apoE(-/-)) mice but not in C57BL/6J mice fed a normal diet after a single inoculation and in both models following repeated inoculation with C. pneumoniae. Repeated inoculation of C57BL/6J mice resulted in inflammatory changes in the heart and aorta in 8 of 40 of mice; however, no atherosclerotic lesion development was observed. Repeated inoculation of apoE(-/-) mice resulted in a statistically significant increase in lesion area (n=43; P=.05). Although Chlamydia trachomatis disseminated to the aorta, persistent infection was not established and no statistically significant increase in lesion area occurred. These studies suggest that persistent infection of the aorta can lead to inflammatory changes in the absence of hyperlipidemia and accelerate lesion progress in concert with hyperlipidemia.

Animals↗

PubMed2000

Development of a syngeneic mouse model for events related to ovarian cancer.

Mouse ovarian surface epithelial cells (MOSEC) were obtained from virgin, mature mice by mild trypsinization and were repeatedly passaged in vitro. Early passage cells (<20 passages) exhibited a cobblestone morphology and contact inhibition of growth. After approximately 20 passages in vitro, cobblestone morphology and contact inhibition of growth was lost. Tumor forming potential was determined by s.c. and i.p. injection of early and late passage cells into athymic and syngeneic C57BL6 mice. Subcutaneous tumors formed in approximately 4 months and were present only at the injection site. Intraperitoneal injection of late passage MOSEC into athymic and syngeneic mice resulted in growth of tumor implants throughout the abdominal cavity, and production of hemorrhagic ascitic fluid. Early passage MOSEC did not form tumors in vivo. Histopathologic analysis of tumors revealed a highly malignant neoplasm containing both carcinomatous and sarcomatous components. Late passage MOSEC expressed cytokeratin and did not produce ovarian steroids in response to gonadotropin stimulation in vitro. Ten clonal lines were established from late passage MOSEC. Each clone formed multiple peritoneal tumors and ascitic fluid after i.p. injection into C57BL6 mice. Three cell lines examined cytogenetically were polyploid with near-tetraploid modal chromosome numbers. Common clonal chromosome gains and losses included +5, +15, +19 and -X, -3, -4. One cell line had a clonal translocation between chromosomes 15 and 18 and another had a small marker chromosome; common structural abnormalities were not observed. These data describe the development of a mouse model for the study of events related to ovarian cancer in humans. The ability of the MOSEC to form extensive tumors within the peritoneal cavity, similar to those seen in women with Stage III and IV cancer, and the ability of the MOSEC to produce tumors in mice with intact immune systems, makes this model unique for investigations of molecular and immune interactions in ovarian cancer development.

Animals↗

PubMedDate not supplied

Production of toxic shock syndrome toxin 1 in a mouse model of Staphylococcus aureus abscess formation.

A mouse model of abscess formation is described in which toxic shock syndrome toxin 1 (TSST-1) is produced by Staphylococcus aureus in vivo. Mice injected intravenously with S. aureus developed renal abscesses within 4-7 days. Kidneys excised from infected mice were cultured quantitatively, and extracts from the kidneys were assayed for TSST-1 with use of a competitive enzyme-linked immunosorbent assay. Animals with less than 10(7) S. aureus/g of kidney had less than 6 ng of TSST-1/mL of extract. Toxin levels ranged from less than 6 ng/mL to 271 ng/mL in kidney extracts from mice with greater than 10(7) S. aureus/g of kidney. Urine from infected mice also contained measurable levels of TSST-1 (range, less than 6-728 ng/mL). Mice developed serum antibodies to TSST-1 by 2 weeks after challenge. Serum samples collected 5-7 days after bacterial challenge did not show biochemical changes typical of a toxic shock-like illness in these animals.

Abscess↗

PubMed1991

Natural history of chronic Staphylococcus epidermidis foreign body infection in a mouse model.

The development and characterization of a mouse model of chronic Staphylococcus epidermidis foreign body infection was done with two clinical isolates that differed in degree of extracellular slime production. Segments of Silastic catheters bearing preformed S. epidermidis biofilms were implanted intraperitoneally, and mice were assessed after 3 and 6 months. Both test strains of S. epidermidis persisted at the implant site through the 6-month follow-up in 80% of the mice, regardless of the degree of slime production. There was no evidence of overt animal morbidity, and microbiologic assessment of other peritoneal sites did not reveal dissemination of bacteria from the infected focus. In comparison with control mice, animals harboring chronic foreign body infection presented marked peripheral neutrophilia and mild anemia.

Animals↗

PubMed1994

Effect of treatment with methicillin and gentamicin in a new experimental mouse model of foreign body infection.

A new mouse model of foreign body infection has been developed. Intraperitoneal placement of a silicone catheter followed by injection of 10(8) Staphylococcus aureus organisms resulted in a reproducible, localized foreign body infection. The infection persisted as an intra-abdominal abscess surrounding the catheter for at least 30 days. Treatment with up to nine doses of methicillin or gentamicin or both was started 3 days after infection. The treatment showed a significant effect (P < 0.05), measured as reduction of bacteria on the foreign body, for all three regimens with a reduction of up to 2 log units, but no synergism was observed. The result of the treatment was poor, despite the facts that the local concentrations of methicillin were greater than the MIC for at least 72 h and that nine peak concentrations of gentamicin of > 13 micrograms/ml were obtained. The poor result of the treatment was not caused by development of antibiotic resistance or influenced by protein concentration, pH, or local presence in the pus of inhibitors of antibiotics. Both antibiotics showed good effects in time-kill studies in vitro on bacteria on catheters taken out of infected mice and catheters infected in vitro. During treatment, the proportion of intracellular bacteria increased in all treated mice to 60 to 75% compared with 20 to 30% in nontreated mice (P < 0.05). This indicates that intracellular survival of staphylococci may influence the outcome of the treatment in foreign body infections.

Animals↗

PubMed2001

Transgenic and knockout mouse models clarify pituitary development, function and disease.

Mouse models have been used to study various aspects of pituitary development, function and disease. Transgenic or knockout technology has been applied to examine the regulation of hormone gene expression and the pathophysiology of its alterations, to ascertain the factors that determine cell differentiation, and to manipulate oncogenesis. Transgenic mice have elucidated the necessary elements required for the tissue- and cell-specific expression of pituitary hormones. Transgenic and knockout technologies have derived mice with hormone overexpression or abrogation of hormone action, and have identified novel hormones. The role of precursor cells in cell differentiation has been confirmed by genetic ablation of cell lineages. Inactivation of transcription factors implicated in pituitary organogenesis and cytogenesis has proven their critical roles in pituitary development. Pituitary oncogenesis has been studied by promoter-directed oncogene expression or tumor suppressor gene ablation, by adenohypophysiotropic hormone overexpression, or by growth factor or receptor overexpression. The tumors have provided a number of cell lines for use in the continuing study of pituitary physiology and pathology. These models may also be used in the future to examine novel therapeutic strategies for the management of patients with pituitary disorders.

Animals↗

PubMed2003

Characterization of a mouse model of allergy to a major occupational latex glove allergen Hev b 5.

Allergen-specific immunotherapy is a clinically proven effective treatment for many allergic diseases, including asthma; however, it is not currently available for latex allergy because of the high risk of anaphylaxis. There is, therefore, a crucial need for an animal model of latex allergy in which to develop effective immunotherapy. Previous mouse models of latex allergy either did not characterize the allergic pulmonary immune response or used crude latex extracts, making it difficult to quantify the contribution of individual proteins and limiting their usefulness for developing specific immunotherapy. We immunized mice with recombinant Hev b 5, a defined major latex allergen, or latex glove protein extract, representing the range of occupationally encountered processed latex allergens. The immune response was compared with that seen in ovalbumin-immunized mice. Immunization with Hev b 5 or glove extract elicits hallmarks of allergic pulmonary Th2-type immune responses, comparable to those for ovalbumin, including (1) serum antigen-specific IgE, (2) an eosinophilic inflammatory infiltrate in the lung, (3) increased interleukin-5 in lung bronchoalveolar lavage fluid, and (4) mucus hypersecretion by epithelial cells in the lung airways. This mouse model will aid the development of potentially curative treatments for latex-sensitized individuals, including those with occupational asthma.

Allergens↗

PubMed2004

Axonal defects in mouse models of motoneuron disease.

Human motoneuron disease is characterized by loss of motor endplates, axonal degeneration, and cell death of motoneurons. The identification of the underlying gene defects for familial ALS, spinal muscular atrophy (SMA), and spinal muscular atrophy with respiratory distress (SMARD) has pointed to distinct pathophysiological mechanisms that are responsible for the various forms of the disease. Accumulating evidence from mouse models suggests that enhanced vulnerability and sensitivity to proapoptotic stimuli is only responsible for some but not all forms of motoneuron disease. Mechanisms that modulate microtubule assembly and the axonal transport machinery are defective in several spontaneous and ENU (ethylnitrososurea) mutagenized mouse models but also in patients with mutations in the p150 subunit of dynactin. Recent evidence suggests that axonal growth defects contribute significantly to the pathophysiology of spinal muscular atrophy. Reduced levels of the survival motoneuron protein that are responsible for SMA lead to disturbed RNA processing in motoneurons. This could also affect axonal transport of mRNAs for beta-actin and other proteins that play an essential role in axon growth and synaptic function. The local translation of specific proteins might be affected, because developing motoneurons contain ribosome-like structures in distal axons and growth cones. Altogether, the evidence from these mouse models and the new genetic data from patients suggest that axon growth and maintenance involves a variety of mechanisms, including microtubule assembly and axonal transport of proteins and ribonucleoproteins (RNPs). Thus, defects in axon maintenance could play a leading role in the development of several forms of human motoneuron disease.

Aged↗

PubMed2000

Transthyretin regulates thyroid hormone levels in the choroid plexus, but not in the brain parenchyma: study in a transthyretin-null mouse model.

Transthyretin (TTR) is the major T4-binding protein in rodents. Using a TTR-null mouse model we asked the following questions. 1) Do other T4 binding moieties replace TTR in the cerebrospinal fluid (CSF)? 2) Are the low whole brain total T4 levels found in this mouse model associated with hypothyroidism, e.g. increased 5'-deiodinase type 2 (D2) activity and RC3-neurogranin messenger RNA levels? 3) Which brain regions account for the decreased total whole brain T4 levels? 4) Are there changes in T3 levels in the brain? Our results show the following. 1) No other T4-binding protein replaces TTR in the CSF of the TTR-null mice. 2) D2 activity is normal in the cortex, cerebellum, and hippocampus, and total brain RC3-neurogranin messenger RNA levels are not altered. 3) T4 levels measured in the cortex, cerebellum, and hippocampus are normal. However T4 and T3 levels in the choroid plexus are only 14% and 48% of the normal values, respectively. 4) T3 levels are normal in the brain parenchyma. The data presented here suggest that TTR influences thyroid hormone levels in the choroid plexus, but not in the brain. Interference with the blood-choroid-plexus-CSF-TTR-mediated route of T4 entry into the brain caused by the absence of TTR does not produce measurable features of hypothyroidism. It thus appears that TTR is not required for T4 entry or for maintenance of the euthyroid state in the mouse brain.

Animals↗