The Effect of Genetic Variation on Inducible Nitric Oxide Synthase Activity
Young, Julia
Young, Julia
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Abstract
Inducible nitric oxide synthase (iNOS, NOS2/Nos2) expression is induced in mammalian innate immune cells in response to immune stimulation. This enzyme produces nitric oxide (NO) which mediates microbial killing, assisting in control of infection. However, excessive NO production by iNOS can damage host tissue and limit long-term immune cell survival, necessitating careful regulation of iNOS activity. One method of iNOS regulation is natural genetic variation; Nos2 coding-region variation in laboratory mouse strains has been previously linked to differential NO production phenotypes. In this study, wild-type human and mouse iNOS variants were evaluated for NO-production, seven amino acid polymorphisms in mouse Nos2 were characterized, and polymorphisms in residue 652/653 identified as significant in determining the NO-production phenotype of iNOS. Experimental results suggest that disruption to the three-dimensional structure of iNOS caused by one polymorphism found in wild-type PWD iNOS is responsible for differences in NO-production. Understanding of the role of genetic variation in driving differential iNOS activity is critical for future research into the health consequences of insufficient or excess iNOS-derived NO.
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Date
1/1/2026
Student Status
Senior (Graduating in 2026)
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Poster
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Molecular Genetics
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College of Agriculture and Life Sciences
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Life Science