Genetic influences on asthma susceptibility in the developing lung.

American Journal of Respiratory Cell and Molecular Biology
Nicole CarpeFeige Kaplan

Abstract

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 ...Continue Reading

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Citations

Sep 18, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nicole CarpeFeige Kaplan
Sep 13, 2011·The Journal of Allergy and Clinical Immunology·Sina A GharibTeal S Hallstrand
Jan 29, 2011·Genetic Testing and Molecular Biomarkers·Essam H Jiffri, Nasser A Elhawary
Nov 30, 2018·Personality & Social Psychology Bulletin·Ledina ImamiRichard B Slatcher
Sep 1, 2017·Social Psychological and Personality Science·Sarah C E StantonRichard B Slatcher
Jul 9, 2014·Expert Review of Clinical Immunology·Jean-Christophe Bérubé, Yohan Bossé
Apr 7, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Lennart K A Lundblad, Annette Robichaud

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