Project description:Insight into the role of Insulin-like Growth Factor (IGF) in development of lungs has come from the study of genetically modified mice. IGF1 is a key factor during lung development. IGF1 deficiency in the neonatal mouse causes respiratory failure collapsed alveoli and altered alveolar septa. To further characterize IGF1 function during lung development we analyzed Igf1-/- mouse prenatal lungs in a C57Bl/6 genetic background. Mutant lungs showed disproportional hypoplasia, disorganized extracellular matrix and dilated alveolar capillaries. IGF1 target genes during lung maturation were identified by analyzing RNA differential expression in Igf1-/- lungs using microarrays. Lungs from E18.5 were isolated from both Igf1+/+ wild type and Igf1-/- null mice and pooled to obtain RNA. Heterozygous male and female with a genetic background C57BL/6J were mated to obtain embryos at embrionic (E) stage 18.5 days post coitum (E18.5). 3 biological replicates per genotype.
Project description:We sequenced mRNA from E18.5 mouse cortex (3 wild-type vs 3 Nova2-/- and 3 wild-type vs 3 Nova1-/-) and from E18.5 mouse mid- and hind-brain (3 wild-type vs 3 Nova1-/-) to compare gene expression level and alternative splicing events between wild-type and Nova mutant mice.
Project description:Deletion of Snx5 leads to respiratory failure in neonatal mice. Here we analyzed the effect of depleted SNX5 in a lung. We used expression microarray to compare between wild lungs and mutant lungs at E18.5 and E18.5 after air-breathing test.
Project description:Insight into the role of Insulin-like Growth Factor (IGF) in development of lungs has come from the study of genetically modified mice. IGF1 is a key factor during lung development. IGF1 deficiency in the neonatal mouse causes respiratory failure collapsed alveoli and altered alveolar septa. To further characterize IGF1 function during lung development we analyzed Igf1-/- mouse prenatal lungs in a C57Bl/6 genetic background. Mutant lungs showed disproportional hypoplasia, disorganized extracellular matrix and dilated alveolar capillaries. IGF1 target genes during lung maturation were identified by analyzing RNA differential expression in Igf1-/- lungs using microarrays.
Project description:Deletion of Snx5 leads to respiratory failure in neonatal mice. Here we analyzed the effect of depleted SNX5 in a lung. We used expression microarray to compare between wild lungs and mutant lungs at E18.5 and E18.5 after air-breathing test. Total RNA were extracted from embryonic 18.5 day (E18.5) wild and mutant mice lung. Also other total RNA samples were extracted after air-breathing test at E18.5.
Project description:Insulin like growth factor 1 (IGF-1) has a central role in mammalian hearing and hearing loss. The auditory and vestibular systems form the inner ear and have a common developmental origin. During chicken early development IGF-1 modulates neurogenesis of the cochleovestibular ganglion but no further studies have been conducted to explore the potential role of IGF-1 in the vestibular system. In this study we have compared the whole transcriptome of the vestibular organ from wild type and Igf1-/- mice at different developmental times. RNA was prepared from E18.5, P15 and P90 vestibular organs of Igf1-/- and Igf1+/+ mice and the transcriptome analyzed in triplicates using Affymetrix® Mouse Gene 1.1 ST Array Plates.
Project description:Vertebrate lonesome kinase (VLK) is the only known secreted tyrosine kinase and responsible for the phosphorylation of a broad range of secretory pathway-resident and extracellular matrix proteins. However, its cell-type specific functions in vivo are still largely unknown. Therefore, we generated mice with a mesenchyme-specific knockout of the VLK gene (protein kinase domain containing, cytoplasmic (Pkdcc)). Most of the homozygous mice die shortly after birth, most likely as a consequence of their lung abnormalities and consequent respiratory failure. E18.5 embryonic lungs showed a reduction of alveolar type II cells, smaller bronchi, and an increased lung tissue density. Global mass spectrometry-based quantitative proteomics identified 112 proteins with significantly and at least 1.5fold differential abundance between genotypes. Twenty-five of these had been assigned to the extracellular region and 15 to the mouse matrisome. Specifically, fibromodulin and matrilin 4, which are involved in extracellular matrix organization, were significantly more abundant in lungs from Pkdcc knockout embryos. These results support a role for mesenchyme-derived VLK in lung development through regulation of matrix dynamics and the resulting non-cell-autonomous modulation of alveolar epithelial cell differentiation.