24 research outputs found

    Hypomorphic mutation of the mouse Huntington's disease gene orthologue

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    Rare individuals with inactivating mutations in the Huntington’s disease gene (HTT) exhibit variable abnormalities that imply essential HTT roles during organ development. Here we report phenotypes produced when increasingly severe hypomorphic mutations in the murine HTT orthologue Htt, (HdhneoQ20, HdhneoQ50, HdhneoQ111), were placed over a null allele (Hdhex4/5). The most severe hypomorphic allele failed to rescue null lethality at gastrulation, while the intermediate, though still severe, alleles yielded recessive perinatal lethality and a variety of fetal abnormalities affecting body size, skin, skeletal and ear formation, and transient defects in hematopoiesis. Comparative molecular analysis of wild-type and Htt-null retinoic acid-differentiated cells revealed gene network dysregulation associated with organ development that nominate polycomb repressive complexes and miRNAs as molecular mediators. Together these findings demonstrate that Htt is required both pre- and post-gastrulation to support normal development

    Targeted Expression of Cre Recombinase Provokes Placental-Specific DNA Recombination in Transgenic Mice

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    Background: Inadequate placental development is associated with a high incidence of early embryonic lethality and serious pregnancy disorders in both humans and mice. However, the lack of well-defined trophoblast-specific gene regulatory elements has hampered investigations regarding the role of specific genes in placental development and fetal growth. Principal Findings: By random assembly of placental enhancers from two previously characterized genes, trophoblast specific protein a (Tpbpa) and adenosine deaminase (Ada), we identified a chimeric Tpbpa/Ada enhancer that when combined with the basal Ada promoter provided the highest luciferase activity in cultured human trophoblast cells, in comparison with non-trophoblast cell lines. We used this chimeric enhancer arrangement to drive the expression of a Cre recombinase transgene in the placentas of transgenic mice. Cre transgene expression occurred throughout the placenta but not in maternal organs examined or in the fetus. Significance: In conclusion, we have provided both in vitro and in vivo evidence for a novel genetic system to achieve placental transgene expression by the use of a chimeric Tpbpa/Ada enhancer driven transgene. The availability of thi

    Evolving missions and university entrepreneurship:Academic spin-offs and graduate start-ups in the entrepreneurial society

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    A recent call has urged to broaden the conceptualization of university entrepreneurship in order to appreciate the heterogeneity of contexts and actors involved in the process of entrepreneurial creation. A gap still persists in the understanding of the variety of ventures generated by different academic stakeholders, and the relationships between these entrepreneurial developments and university missions, namely, teaching and research. This paper addresses this particular gap by looking at how university teaching and research activities influence universities’ entrepreneurial ventures such as academic spin-offs and graduate start-ups. Empirically, we analyse the English higher education sector, drawing on institutional data at the university level. First, we explore the ways in which teaching and research activities are configured, and secondly, we examine how such configurations relate to academic spin-offs and graduate start-ups across different universities over time. Our findings suggest, first, that the evolution of USOs and graduate start-ups exhibit two different pathways over time; and second, that teaching and research both affect entrepreneurial ventures but their effect is different.JRC.B.4-Human Capital and Employmen
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