Pleiotropic effects in Eya3 knockout mice

<p>Abstract</p> <p>Background</p> <p>In <it>Drosophila</it>, mutations in the gene <it>eyes absent </it>(<it>eya</it>) lead to severe defects in eye development. The functions of its mammalian orthologs <it>Eya1-4 </it>are only partially understood and no mouse model exists for <it>Eya3</it>. Therefore, we characterized the phenotype of a new <it>Eya3 </it>knockout mouse mutant.</p> <p>Results</p> <p>Expression analysis of <it>Eya3 </it>by <it>in-situ </it>hybridizations and β-Gal-staining of <it>Eya3 </it>mutant mice revealed abundant expression of the gene throughout development, e.g. in brain, eyes, heart, somites and limbs suggesting pleiotropic effects of the mutated gene. A similar complex expression pattern was observed also in zebrafish embryos.</p> <p>The phenotype of young adult <it>Eya3 </it>mouse mutants was systematically analyzed within the German Mouse Clinic. There was no obvious defect in the eyes, ears and kidneys of <it>Eya3 </it>mutant mice. Homozygous mutants displayed decreased bone mineral content and shorter body length. In the lung, the tidal volume at rest was decreased, and electrocardiography showed increased JT- and PQ intervals as well as decreased QRS amplitude. Behavioral analysis of the mutants demonstrated a mild increase in exploratory behavior, but decreased locomotor activity and reduced muscle strength. Analysis of differential gene expression revealed 110 regulated genes in heart and brain. Using real-time PCR, we confirmed <it>Nup155 </it>being down regulated in both organs.</p> <p>Conclusion</p> <p>The loss of <it>Eya3 </it>in the mouse has no apparent effect on eye development. The wide-spread expression of <it>Eya3 </it>in mouse and zebrafish embryos is in contrast to the restricted expression pattern in <it>Xenopus </it>embryos. The loss of <it>Eya3 </it>in mice leads to a broad spectrum of minor physiological changes. Among them, the mutant mice move less than the wild-type mice and, together with the effects on respiratory, muscle and heart function, the mutation might lead to more severe effects when the mice become older. Therefore, future investigations of <it>Eya3 </it>function should focus on aging mice.</p

The Validity and Structure of Culture-Level Personality Scores: Data From Ratings of Young Adolescents

We examined properties of culture-level personality traits in ratings of targets (N=5,109) ages 12 to 17 in 24 cultures. Aggregate scores were generalizable across gender, age, and relationship groups and showed convergence with culture-level scores from previous studies of self-reports and observer ratings of adults, but they were unrelated to national character stereotypes. Trait profiles also showed cross-study agreement within most cultures, 8 of which had not previously been studied. Multidimensional scaling showed that Western and non-Western cultures clustered along a dimension related to Extraversion. A culture-level factor analysis replicated earlier findings of a broad Extraversion factor but generally resembled the factor structure found in individuals. Continued analysis of aggregate personality scores is warranted. This article is a US Government work and is in the public domain in the USA.Fil: McCrae, Robert R.. National Institute on Ageing; CanadáFil: Terracciano, Antonio. National Institute on Ageing; CanadáFil: De Fruyt, Filip. University of Ghent; BélgicaFil: De Bolle, Marleen. University of Ghent; BélgicaFil: Gelfand, Michele J.. University of Maryland; Estados UnidosFil: Costa Jr., Paul T.. National Institute on Ageing; CanadáFil: Klinkosz, Waldemar. The John Paul II Catholic University of Lublin; PoloniaFil: Knežević, Goran. Belgrade University; SerbiaFil: Leibovich de Figueroa, Nora. Universidad de Buenos Aires; ArgentinaFil: Löckenhoff, Corinna E.. Cornell University; Estados UnidosFil: Martin, Thomas A.. Susquehanna University; Estados UnidosFil: Marušić, Iris. Institute for Social Research; CroaciaFil: Mastor, Khairul Anwar. Universiti Kebangsaan Malaysia; MalasiaFil: Nakazato, Katsuharu. Iwate Prefectural University; AfganistánFil: Nansubuga, Florence. Makerere University; UgandaFil: Porrata, Jose. No especifíca;Fil: Purić, Danka. Belgrade University; SerbiaFil: Realo, aAnu. University of Tartu; EstoniaFil: Reátegui, Norma. Universidad Peruana Cayetano Heredia; PerúFil: Rolland, Jean Pierre. Universite Paris Ouest Nanterre la Defense; FranciaFil: Schmidt, Vanina Ines. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sekowski, Andrzej. The John Paul II Catholic University of Lublin; PoloniaFil: Shakespeare Finch, Jane. Queensland University of Technology; AustraliaFil: Shimonaka, Yoshiko. Bunkyo Gakuin University; JapónFil: Simonetti, Franco. Pontificia Universidad Católica de Chile; ChileFil: Siuta, Jerzy. Jagiellonian University;Fil: Szmigielska, Barbara. Jagiellonian University;Fil: Vanno, Vitanya. Srinakharinwirot University; TailandiaFil: Wang, Lei. Peking University; ChinaFil: Yik, Michelle. The Hong Kong University of Science and Technology; Hong Kon

Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis.

BACKGROUND 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. Distribution of 20-nm titanium dioxide NP in lungs was assessed on ultrathin sections immediately and 24 h after a one-hour NP inhalation. NP biokinetics was deduced from total and regional lung deposition and from whole body translocation of inhaled 30-nm iridium NP within 24 h after aerosol inhalation. Inflammatory responses were assessed within 7 days after carbon NP instillation. RESULTS Cftr mutant females had moderately reduced lung compliance and slightly increased airway resistance compared to wild type mice. We found no genotype dependent differences in total, regional and head deposition or in secondary-organ translocation of inhaled iridium NP. Titanium dioxide inhalation resulted in higher NP uptake by alveolar epithelial cells in Cftr mutants. Instillation of carbon NP induced a comparable acute and transient inflammatory response in both genotypes. The twofold increase of bronchoalveolar lavage (BAL) neutrophils in Cftr mutant compared to wild type mice at day 3 but not at days 1 and 7, indicated an impaired capacity in inflammation resolution in Cftr mutants. Concomitant to the delayed decline of neutrophils, BAL granulocyte-colony stimulating factor was augmented in Cftr mutant mice. Anti-inflammatory 15-hydroxyeicosatetraenoic acid was generally significantly lower in BAL of Cftr mutant than in wild type mice. CONCLUSIONS Despite lacking alterations in lung deposition and biokinetics of inhaled NP, and absence of significant differences in lung function, higher uptake of NP by alveolar epithelial cells and prolonged, acute inflammatory responses to NP exposure indicate a moderately increased susceptibility of lungs to adverse effects of inhaled NP in Cftr mutant mice and provides potential mechanisms for the increased susceptibility of CF patients to air pollution