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Disruption of sorting nexin 5 causes respiratory failure associated with undifferentiated alveolar epithelial type I cells in mice

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE37080 | GEO | 2012/12/31

SECONDARY ACCESSION(S): PRJNA158099

REPOSITORIES: GEO

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Disruption of sorting nexin 5 causes respiratory failure associated with undifferentiated alveolar epithelial type I cells in 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. 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.

2012-12-31 | E-GEOD-37080 | biostudies-arrayexpress

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Transcriptome Analysis of Tra Catfish (Pangasianodon hypophthalmus) Early Development Provides Novel Insights for the Terrestrial Adaptation

Project description:Channel catfish (Ictalurus punctatus) and tra catfish (Pangasianodon hypophthalmus) both belong to the order Siluriformes. Channel catfish does not possess an air-breathing organ (ABO), and thus cannot breathe in the air, while tra catfish is a facultative air-breather and use the swim bladder as its air-breathing organ, which provides for aerial breathing in low oxygen conditions. Tra and channel catfish serve as a great comparative model for studying the transition of life from water to terrestrial living, as well as for understanding genes that are crucial for development of the swim bladder and the function of air-breathing in tra catfish. We selected seven developmental stages in tra catfish for RNA-Seq analysis based on their transition to a stage that could live at 0 ppm oxygen. More than 587 million sequencing clean reads were generated in tra catfish, and a total of 21, 448 unique genes were detected. A comparative genomic analysis was conducted between channel catfish and tra catfish. Gene expression analysis was performed for these tra catfish specific genes. Hypoxia challenge and microtomy experiments collectively suggested that there are critical timepoints for the development of the air-breathing function and swim bladder development stages in tra catfish. Key genes were identified to be the best candidates of genes related to the air-breathing ability in tra catfish. This study provides a large data resource for functional genomic studies in air-breathing function in tra catfish, and sheds light on the adaption of aquatic organisms to the terrestrial environment.

2021-01-12 | GSE154904 | GEO

Comparative genomic analysis revealed twenty-six candidate genes involved in the air-breathing function of the broadhead catfish Clarias macrocephalus

Project description:Walking catfish (Clarias macrocephalus) and channel catfish (Ictalurus punctatus) are freshwater fish species of the Siluriformes order. C. macrocephalus has both gills and modified gill structures serving as an air breathing organ (ABO) which allows them aerial breathing (AB), while I. punctatus does not possess an air-breathing organ (ABO), and thus cannot breathe in air. These two species provide an excellent model for studying the molecular basis of accessory air-breathing organ development in teleost fish. In this study, seven development stages in C. macrocephalus were selected for RNA-seq analysis to compare with channel catfish as the time when air breathing organ developed and became functional. Through comparative genetic contents analysis, 1,458 genes were identified to be present in C. macrocephalus, but absent from I. punctatus. Gene expression analysis and protein-protein intersection (PPI) analysis were performed, 26 genes were selected in C. macrocephalus, including mb, ngb, hbae genes, which are mainly associated with oxygen carrier activity, oxygen binding and heme binding activities. Our work provides a large data resource for exploring the genomic basis of air breathing function in C. macrocephalus and offers an insight into the adaption of aquatic organisms to hypoxia and high ammonia environment.

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Disordered breathing in Pitt Hopkins syndrome involves disruption of parafacial respiratory neurons and aberrant expression of Nav1.8.

Project description:Pitt-Hopkins syndrome (PTHS) is a rare autism spectrum-like disorder characterized by intellectual disability, developmental delays and breathing problems involving episodes of hyperventilation followed by apnea. PTHS is caused by functional haploinsufficiency of the gene encoding transcription factor 4 (Tcf4). Despite the severity of this disease, virtually nothing is known regarding mechanisms contributing to PTHS behavioral abnormalities, and candidate therapeutic targets are lacking. Here, we show that a Tcf4 truncation (Tcf4tr/+) mouse model of PTHS recapitulates respiratory phenotypes observed in PTHS patients. The basis of this behavior deficit involves selective loss of putative expiratory parafacial neurons and compromised function of neurons in the retrotrapezoid nucleus that regulate breathing in response to tissue CO2/H+. We also show that central Nav1.8 channels can be targeted pharmacologically to improve respiratory function at the cellular and behavioral levels in Tcf4tr/+ mice, thus establishing Nav1.8 as a high priority target with therapeutic potential in PTHS.

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Haploinsufficiency of Hedgehog interacting protein causes increased emphysema induced by cigarette smoke through network rewiring

Project description:BACKGROUND: The HHIP gene, encoding Hedgehog interacting protein, has been implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS), and our subsequent studies identified a functional upstream genetic variant that decreased HHIP transcription. However, little is known about how HHIP contributes to COPD pathogenesis. METHODS: Here, we exposed Hhip haploinsufficient mice (Hhip+/-) to cigarette smoke (CS) for 6 months to model the biological consequences caused by CS in human COPD risk-allele carriers at the HHIP locus. Gene expression profiling in murine lungs was performed followed by an integrative network inference analysis, PANDA (Passing Attributes between Networks for Data Assimilation) analysis. RESULTS: We detected more severe airspace enlargement in Hhip+/- mice vs. wild-type littermates (Hhip+/+) exposed to CS. Gene expression profiling in murine lungs suggested enhanced lymphocyte activation pathways in CS-exposed Hhip+/- vs. Hhip+/+ mice, which was supported by increased numbers of lymphoid aggregates and enhanced activation of CD8+ T cells after CS-exposure in the lungs of Hhip+/- mice compared to Hhip+/+ mice. Mechanistically, results from PANDA network analysis suggested a rewired and dampened Klf4 signaling network in Hhip+/- mice after CS exposure. CONCLUSIONS: In summary, HHIP haploinsufficiency exaggerated CS-induced airspace enlargement, which models CS-induced emphysema in human smokers carrying COPD risk alleles at the HHIP locus. Network modeling suggested rewired lymphocyte activation signaling circuits in the HHIP haploinsufficiency state. Total RNA was obtained from the lung tissue of C57BL/6J mice exposed to cigarette smoke (CS) or filtered air (air) for 6 months. Six mice from each of four groups with different genotypes (Hhip+/+ or Hhip+/-) and treatments (air or CS) were randomly chosen for gene expression profiling

2015-01-21 | E-GEOD-65124 | biostudies-arrayexpress

Transcription profiling by array of human blood after single and successive SCUBA dives with different breathing gas compositions

Project description:Characterization of gene expression in blood after single and repetitive SCUBA diving to 18 meters while breathing compressed air or a mixture of 36 percent oxygen and 64 percent nitrogen.

2012-07-07 | E-MTAB-1179 | biostudies-arrayexpress

Misgurnus anguillicaudatus

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