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Licensed Unlicensed Requires Authentication Published by De Gruyter July 18, 2018

Neonatal Ogg1/Mutyh knockout mice have altered inflammatory gene response compared to wildtype mice in the brain and lung after hypoxia-reoxygenation

  • Anne Gro W. Rognlien EMAIL logo , Embjørg J. Wollen , Monica Atneosen-Åsegg , Rajikala Suganthan , Magnar Bjørås and Ola Didrik Saugstad

Abstract

Background

8-Oxoguanine DNA-glycosylase 1 (OGG1) and mutY DNA glycosylase (MUTYH) are crucial in the repair of the oxidative DNA lesion 7,8-dihydro-8-oxoguanine caused by hypoxia-reoxygenation injury. Our objective was to compare the gene expression changes after hypoxia-reoxygenation in neonatal Ogg1-Mutyh double knockout mice (OM) and wildtype mice (WT), and study the gene response in OM after hyperoxic reoxygenation compared to normoxic.

Methods

Postnatal day 7 mice were subjected to 2 h of hypoxia (8% O2) followed by reoxygenation in either 60% O2 or air, and sacrificed right after completed reoxygenation (T0h) or after 72 h (T72h). The gene expression of 44 a priori selected genes was examined in the hippocampus/striatum and lung.

Results

We found that OM had an altered gene response compared to WT in 21 genes in the brain and 24 genes in the lung. OM had a lower expression than WT of inflammatory genes in the brain at T0h, and higher expression at T72h in both the brain and lung. In the lung of OM, five genes were differentially expressed after hyperoxic reoxygenation compared to normoxic.

Conclusion

For the first time, we report that Ogg1 and Mutyh in combination protect against late inflammatory gene activation in the hippocampus/striatum and lung after neonatal hypoxia-reoxygenation.

Acknowledgments

The authors are grateful for the assistance of Grethe Dyrhaug, Maren Bakkebø, the staff at Comparative medicine, Oslo University hospital, statistician Are Hugo Pripp and the Epigen lab at Akershus University hospital.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2018-0172).


Received: 2017-09-25
Accepted: 2018-06-15
Published Online: 2018-07-18
Published in Print: 2018-12-19

©2019 Walter de Gruyter GmbH, Berlin/Boston

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