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Genetic Influences on Asthma Susceptibility in Developing Lung

ABSTRACT: Whole transcriptome assay of whole lung of rat from 3 genetic strains (Lewis, Fisher, Brown Norway) at 3 postnatal time points (postnatal days 1, 7, 14).

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE19666 | GEO | 2009/12/28

SECONDARY ACCESSION(S): PRJNA122483

REPOSITORIES: GEO

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Genetic Influences on Asthma Susceptibility in Developing Lung

Project description:Whole transcriptome assay of whole lung of rat from 3 genetic strains (Lewis, Fisher, Brown Norway) at 3 postnatal time points (postnatal days 1, 7, 14). Total RNA obtained from whole lung of rat from 3 genetic strains and 3 postnatal time points in (mainly) quadruplicate measurements per strain and time point.

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Genetic influences on asthma susceptibility in the developing lung.

Project description:Asthma is the leading serious pediatric chronic illness in the United States, affecting 7.1 million children. The prevalence of asthma in children under 4 years of age has increased dramatically in the last 2 decades. Existing evidence suggests that this increase in prevalence derives from early environmental exposures acting on a pre-existing asthma-susceptible genotype. We studied the origins of asthma susceptibility in developing lung in rat strains that model the distinct phenotypes of airway hyperresponsiveness (Fisher rats) and atopy (brown Norway [BN] rats). Postnatal BN rat lungs showed increased epithelial proliferation and tracheal goblet cell hyperplasia. Fisher pups showed increased lung resistance at age 2 weeks, with elevated neutrophils throughout the postnatal period. Diverse transcriptomic signatures characterized the distinct respiratory phenotypes of developing lung in both rat models. Linear regression across age and strain identified developmental variation in expression of 1,376 genes, and confirmed both strain and temporal regulation of lung gene expression. Biological processes that were heavily represented included growth and development (including the T Box 1 transcription factor [Tbx5], the epidermal growth factor receptor [Egfr], the transforming growth factor beta-1-induced transcript 1 [Tgfbr1i1]), extracellular matrix and cell adhesion (including collagen and integrin genes), and immune function (including lymphocyte antigen 6 (Ly6) subunits, IL-17b, Toll-interacting protein, and Ficolin B). Genes validated by quantitative RT-PCR and protein analysis included collagen III alpha 1 Col3a1, Ly6b, glucocorticoid receptor and Importin-13 (specific to the BN rat lung), and Serpina1 and Ficolin B (specific to the Fisher lung). Innate differences in patterns of gene expression in developing lung that contribute to individual variation in respiratory phenotype are likely to contribute to the pathogenesis of asthma.

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In utero allergen exposure reprograms primary developmental patterns of lung gene expression and influences respiratory phenotype in rat models of asthma susceptibility.

Project description:Transcriptome of whole lung of rat from 3 genetic strains, 3 postnatal time points and 2 exposures (saline versus ovalbumin) in (mainly) 4 replicate measurements per condition. Total RNA obtained from whole lung of rat from 3 genetic strains, 3 postnatal time points and 2 exposures (saline versus ovalbumin) in (mainly) 4 replicate measurements per condition.

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In utero allergen exposure reprograms primary developmental patterns of lung gene expression and influences respiratory phenotype in rat models of asthma susceptibility.

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Development of microRNA signatures for acute rejection after liver transplantation using rat model

Project description:To find out acute rejection (AR) associated microRNAs, we have employed Agilent microRNA microarray as a discovery platform to identify microRNAs with the potential to distinguish AR from controls. We first established a rat Orthotopic liver transplantation (OLT) model with AR, using Brown Norway (BN) rats that received OLT with liver grafts from Lewis rats (Lewis to BN). OLT with BN rats as the donors and recipients were also performed (BN to BN), and these rats served as the control group (non-rejection group, NR group). Then, global microRNA expression profiles of the plasma and grafts were evaluated and validated with high throughout microarray and RT-qPCR.

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