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.
View Article and Find Full Text PDFBackground: Persons with cystic fibrosis (CF) are at-risk for health effects from ambient air pollution but little is known about the interaction of nanoparticles (NP) with CF lungs. Here we study the distribution of inhaled NP in a murine CF model and aim to reveal mechanisms contributing to adverse effects of inhaled particles in susceptible populations.
Methods: Chloride channel defective CftrTgH (neoim) Hgu mice were used to analyze lung function, lung distribution and whole body biokinetics of inhaled NP, and inflammatory responses after intratracheal administration of NP.
Aging and neurodegeneration are often accompanied by a functionally impaired ubiquitin-proteasome system (UPS). In tauopathies and polyglutamine diseases, a mutant form of ubiquitin B (UBB(+1)) accumulates in disease-specific aggregates. UBB(+1) mRNA is generated at low levels in vivo during transcription from the ubiquitin B locus by molecular misreading.
View Article and Find Full Text PDFJ Appl Physiol (1985)
March 2012
Little is known about the effects of postnatal developmental changes in lung architecture and breathing patterns on intrapulmonary particle deposition. We measured deposition in the developing Wistar-Kyoto rat, whose lung development largely parallels that of humans. Deposition of 2-μm sebacate particles was determined in anesthetized, intubated, spontaneously breathing rats on postnatal days (P) 7 to 90 by aerosol photometry (Karrasch S, Eder G, Bolle I, Tsuda A, Schulz H.
View Article and Find Full Text PDFA 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 )).
View Article and Find Full Text PDFIt 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.
View Article and Find Full Text PDFWith 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.
View Article and Find Full Text PDFBackground: In Drosophila, mutations in the gene eyes absent (eya) lead to severe defects in eye development. The functions of its mammalian orthologs Eya1-4 are only partially understood and no mouse model exists for Eya3. Therefore, we characterized the phenotype of a new Eya3 knockout mouse mutant.
View Article and Find Full Text PDFJ Aerosol Med Pulm Drug Deliv
September 2008
Rats are used to test the toxicological and pharmacological effects of aerosol particles on the organism. For estimates of the delivered aerosol dose, lung deposition models provide a valuable tool. Here a previously developed deposition model for nonhygroscopic and hygroscopic aerosol particles in the lungs of man (Ferron et al.
View Article and Find Full Text PDFLittle is known about lung function during early stages of postnatal maturation, although the complex structural changes associated with developing rat lung are well studied. We therefore analyzed corresponding functional (lung volume, respiratory mechanics, intrapulmonary gas mixing, and gas exchange) and structural (alveolar surface area, mean linear intercept length, and alveolar septal thickness) changes of the developing rat lung at 7-90 days. Total lung capacity (TLC) increased from 1.
View Article and Find Full Text PDFImpaired development and reduced lung capacity are risk factors of asthma and chronic obstructive pulmonary disease. Previously, our genomewide linkage analysis of C3H/HeJ (C3H) and JF1/Msf (JF1) mouse strains identified quantitative trait loci (QTLs) associated with the complex traits of dead space volume (Vd), total lung capacity (TLC), lung compliance (CL), and diffusing capacity for CO (D(CO)). We assessed positional candidate genes by comparing C3H with JF1 lung transcript levels by microarray and by comparing C3H, BALB/cByJ, C57BL/6J, A/J, PWD/PhJ, and JF1 strains, using exon sequencing to predict protein structure.
View Article and Find Full Text PDFMinipigs are widely used to examine physiologic mechanisms under experimental settings. The purpose of our study was to localize the visual cortex of minipigs using visual stimulation in functional magnetic resonance imaging (fMRI). Five male Göttinger minipigs were studied with fMRI during visual stimulation with series of light impulses conducted into the MR cabin via fibre optical wave guides (EPI sequences, block design, 1.
View Article and Find Full Text PDFThere is a need for prolonged anesthesia procedures in experimental surgery. Animals in this study received fentanyl, Midazolam, and Propofol administered by continuous intravenous infusion for anesthesia along with controlled ventilation. Time of anesthesia was 413 +/- 95 min.
View Article and Find Full Text PDFGraefes Arch Clin Exp Ophthalmol
December 2003
Background: To test the function of implantable devices for electrical stimulation of the retina, long-term registration tests of cortical-evoked potentials are required. Skin electrodes are not appropriate to provide representative recordings, due to the voluminous pneumatic frontal sinus of minipigs. Therefore, epidural electrodes were permanently implanted in minipigs and tested with visual and electrical retinal stimulation.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
March 2003
Pretreatment with tumor necrosis factor-alpha (TNF-alpha) antibodies abolishes myocardial infarct size reduction by late ischemic preconditioning (IP). Whether or not TNF-alpha is also important for myocardial infarct size reduction by classic IP is unknown. Anesthetized rabbits were untreated (group 1, n = 7), classically preconditioned by 5 min left coronary artery occlusion/10 min reperfusion (group 2, n = 6), or pretreated with TNF-alpha antibodies without (group 3, n = 6) or with IP (group 4, n = 6) before undergoing 30 min of occlusion and 180 min of reperfusion.
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