Complex Long-term Effects of Radiation on Adult Mouse Behavior.

We have shown previously that a single radiation event (0.063, 0.125 or 0.

Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds.

Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in EU member states. The EU CONCERT LDLensRad project was initiated to further understand the effects of ionizing radiation on the lens and identify the mechanism(s) involved in radiation-induced cataract, as well as the impact of dose and dose-rate.

Radiation-induced DNA Damage and Repair in Lens Epithelial Cells of both Ptch1(+/-) and Ercc2(+/-) Mutated Mice.

Epidemiological studies suggest an increased incidence and risk of cataract after low-dose (<2 Gy) ionizing radiation exposures. However, the biological mechanism(s) of this process are not fully understood. DNA damage and repair are thought to have a contributing role in radiation-induced cataractogenesis.

On the Nature of Murine Radiation-Induced Subcapsular Cataracts: Optical Coherence Tomography-Based Fine Classification, In Vivo Dynamics and Impact on Visual Acuity.

Ionizing radiation is widely known to induce various kinds of lens cataracts, of which posterior subcapsular cataracts (PSCs) have the highest prevalence. Despite some studies regarding the epidemiology and biology of radiation-induced PSCs, the mechanism underscoring the formation of this type of lesions and their dose dependency remain uncertain. Within the current study, our team investigated the in vivo characteristics of PSCs in B6C3F1 mice (F1-hybrids of BL6 × C3H) that received 0.

Transcriptomic landscape of radiation-induced murine thyroid proliferative lesions.

Thyroid carcinoma incidence rates in western societies are among the fastest rising, compared to all malignant tumors over the past two decades. While risk factors such as age and exposure to ionizing radiation are known, early-state carcinogenic processes or pre-lesions are poorly understood or unknown. This study aims at the identification and characterization of early-state radiation-associated neoplastic processes by histologic and transcriptomic analyses of thyroid tissues derived from a mouse model.

Posterior subcapsular cataracts are a late effect after acute exposure to 0.5 Gy ionizing radiation in mice.

Purpose: The long-term effect of low and moderate doses of ionizing radiation on the lens is still a matter of debate and needs to be evaluated in more detail.

Material And Methods: We conducted a detailed histological analysis of eyes from B6C3F1 mice cohorts after acute gamma irradiation (Co source; 0.063 Gy/min) at young adult age of 10 weeks with doses of 0.

Ionising radiation causes vision impairment in neonatal B6C3F1 mice.

Ionising radiation interacts with lenses and retinae differently. In human lenses, posterior subcapsular cataracts are the predominant observation, whereas retinae of adults are comparably resistant to even relatively high doses. In this study, we demonstrate the effects of 2 Gy of low linear energy transfer ionising radiation on eyes of B6C3F1 mice aged postnatal day 2.

Imbalances in the eye lens proteome are linked to cataract formation.

The prevalent model for cataract formation in the eye lens posits that damaged crystallin proteins form light-scattering aggregates. The α-crystallins are thought to counteract this process as chaperones by sequestering misfolded crystallin proteins. In this scenario, chaperone pool depletion would result in lens opacification.

Radiation-induced lens opacities: Epidemiological, clinical and experimental evidence, methodological issues, research gaps and strategy.

In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts.

Dose-dependent long-term effects of a single radiation event on behaviour and glial cells.

Purpose: The increasing use of low-dose ionizing radiation in medicine requires a systematic study of its long-term effects on the brain, behaviour and its possible association with neurodegenerative disease vulnerability. Therefore, we analysed the long-term effects of a single low-dose irradiation exposure at 10 weeks of age compared to medium and higher doses on locomotor, emotion-related and sensorimotor behaviour in mice as well as on hippocampal glial cell populations.

Materials And Methods: We determined the influence of radiation dose (0, 0.

Mutation in Bmpr1b Leads to Optic Disc Coloboma and Ventral Retinal Gliosis in Mice.

Purpose: The clinical phenotype of retinal gliosis occurs in different forms; here, we characterize one novel genetic feature, (i.e., signaling via BMP-receptor 1b).

Spectral domain - Optical coherence tomography (SD-OCT) as a monitoring tool for alterations in mouse lenses.

The eye lens displays a variety of phenotypes in the wake of genetic modifications or environmental influences. Therefore, a high-resolution in vivo imaging method for the lens is desirable. Optical coherence tomography (OCT) has become a powerful imaging tool in ophthalmology, especially for retinal imaging in small animal models such as mice.

CREB Signaling Mediates Dose-Dependent Radiation Response in the Murine Hippocampus Two Years after Total Body Exposure.

The impact of low-dose ionizing radiation (IR) on the human brain has recently attracted attention due to the increased use of IR for diagnostic purposes. The aim of this study was to investigate low-dose radiation response in the hippocampus. Female B6C3F1 mice were exposed to total body irradiation with 0 (control), 0.

Lifetime study in mice after acute low-dose ionizing radiation: a multifactorial study with special focus on cataract risk.

Because of the increasing application of ionizing radiation in medicine, quantitative data on effects of low-dose radiation are needed to optimize radiation protection, particularly with respect to cataract development. Using mice as mammalian animal model, we applied a single dose of 0, 0.063, 0.

Influence of Select Antibiotics on Vibrio fischeri and Desmodesmus subspicatus at μg L Concentrations.

The presence of pharmaceuticals in the aquatic environment is a contemporary reality and it is necessary to understand more about the effects of this presence on organisms. The purpose of this work was to assess the ecotoxicity of antibiotics metronidazole, nitrofurantoin, trimethoprim, and sulphamethoxazole (single and mixture) in Vibrio fischeri and Desmodesmus subspicatus at μg L concentrations. The evaluation of the toxic effect of the antibiotics on V.

Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.

The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2Gy.

New mutation in the mouse Xpd/Ercc2 gene leads to recessive cataracts.

Cataracts are the major eye disorder and have been associated mainly with mutations in lens-specific genes, but cataracts are also frequently associated with complex syndromes. In a large-scale high-throughput ENU mutagenesis screen we analyzed the offspring of paternally treated C3HeB/FeJ mice for obvious dysmorphologies. We identified a mutant suffering from rough coat and small eyes only in homozygotes; homozygous females turned out to be sterile.

Standardized, systemic phenotypic analysis of Slc12a1I299F mutant mice.

Background: Type I Bartter syndrome is a recessive human nephropathy caused by loss-of-function mutations in the SLC12A1 gene coding for the Na+-K+-2Cl- cotransporter NKCC2. We recently established the mutant mouse line Slc12a1I299F exhibiting kidney defects highly similar to the late-onset manifestation of this hereditary human disease. Besides the kidney defects, low blood pressure and osteopenia were revealed in the homozygous mutant mice which were also described in humans.

Are mouse lens epithelial cells more sensitive to γ-irradiation than lymphocytes?

In this pilot study we compared for the first time the radiation sensitivity of mouse lens epithelial cells (LECs) and mouse lymphocytes. We freshly prepared LECs and lymphocytes and irradiated them with γ-rays ((137)Cs; doses ranging from 0.25 to 2 Gy).

Differences in the susceptibility to iodine¹³¹-induced thyroid tumours amongst inbred mouse strains.

Genetic factors can modify susceptibility to the carcinogenic effect of ionising radiation. To establish if radioiodine-induced thyroid cancer is similarly genetically influenced, we studied F1 hybrid crosses between inbred mouse strains. Mice were perinatally exposed to iodine-131 and thyroid tissues examined after 18 months.

Microphthalmia, parkinsonism, and enhanced nociception in Pitx3 ( 416insG ) mice.

A new spontaneous mouse mutant was characterized by closed eyelids at weaning and without apparent eyes (provisional gene name, eyeless; provisional gene symbol, eyl). The mutation follows a recessive pattern of inheritance and was mapped to the region of chromosome 19 containing Pitx3. Genetic complementation tests using Pitx3 ( ak/+ ) mice confirmed eyl as a new allele of Pitx3 (Pitx3 ( eyl )).

Reduced corneal thickness and enlarged anterior chamber in a novel ColVIIIa2G257D mutant mouse.

Purpose: The purpose of this study was the morphologic and genetic characterization of the novel eye size mutant Aca23 in the mouse.

Methods: The eyes of the mutants were characterized in vivo by optical low-coherence interferometry, Scheimpflug imaging, and funduscopy. Visual acuity was examined using a virtual optomotor system.

A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.

It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia.

Systemic first-line phenotyping.

With the completion of the mouse genome sequence an essential task for biomedical sciences in the twenty-first century will be the generation and functional analysis of mouse models for every gene in the mammalian genome. More than 30,000 mutations in ES cells will be engineered and thousands of mouse disease models will become available over the coming years by the collaborative effort of the International Mouse Knockout Consortium. In order to realize the full value of the mouse models proper characterization, archiving and dissemination of mouse disease models to the research community have to be performed.