Genetic determinants of ammonia-induced acute lung injury in mice.

American journal of physiology. Lung cellular and molecular physiology 2021 Jan 01

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In this study, a genetically diverse panel of 43 mouse strains was exposed to ammonia, and genome-wide association mapping was performed employing a single-nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was used to help resolve the genetic determinants of ammonia-induced acute lung injury. The encoded proteins were prioritized based on molecular function, nonsynonymous SNP within a functional domain or SNP within the promoter region that altered expression. This integrative functional approach revealed 14 candidate genes that included Aatf, Avil, Cep162, Hrh4, Lama3, Plcb4, and Ube2cbp, which had significant SNP associations, and Aff1, Bcar3, Cntn4, Kcnq5, Prdm10, Ptcd3, and Snx19, which had suggestive SNP associations. Of these genes, Bcar3, Cep162, Hrh4, Kcnq5, and Lama3 are particularly noteworthy and had pathophysiological roles that could be associated with acute lung injury in several ways.

Citation

Kiflai Bein, Koustav Ganguly, Timothy M Martin, Vincent J Concel, Kelly A Brant, Y P Peter Di, Swapna Upadhyay, James P Fabisiak, Louis J Vuga, Naftali Kaminski, Emrah Kostem, Eleazar Eskin, Daniel R Prows, Ann-Soo Jang, George D Leikauf. Genetic determinants of ammonia-induced acute lung injury in mice. American journal of physiology. Lung cellular and molecular physiology. 2021 Jan 01;320(1):L41-L62