Michael D Hoos
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Michael D Hoos has a total of 7 co-authors. Here are the top co-authors by number of shared publications:
- Angela Everhart
Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA
1 shared publication - Carol A. Colton
Duke University Medical Center
1 shared publication - David A. Wink
Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, USA
1 shared publication - Joan Wilson
Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA
1 shared publication - Lisa A. Ridnour
Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, USA
1 shared publication - Marilyn Jansen
Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA
1 shared publication
Latest Publications
- Open Access
- 17 November 2014
- Published by Springer Nature in Molecular Neurodegeneration
- Vol. 9 (1) , 50
The impact of human and mouse differences in NOS2 gene expression on the brain’s redox and immune environment
Mouse models are used in the study of human disease. Despite well-known homologies, the difference in immune response between mice and humans impacts the application of data derived from mice to human disease outcomes. Nitric oxide synthase-2 (NOS2) is a key gene that displays species-specific outcomes via altered regulation of the gene promoter and via post-transcriptional mechanisms in humans that are not found in mice. The resulting levels of NO produced by activation of human NOS2 are different from the levels of NO produced by mouse Nos2. Since both tissue redox environment and immune responsiveness are regulated by the level of NO and its interactions, we investigated the significance of mouse and human differences on brain oxidative stress and on immune activation in HuNOS2 tg /mNos2 -/- mice that express the entire human NOS2 gene and that lack a functional mNos2 compared to wild type (WT) mice that express normal mNos2. Similarly to human, brain tissue from HuNOS2 tg /mNos2 -/- mice showed the presence of a NOS2 gene 3′UTR binding site. We also identified miRNA-939, the binding partner for this site, in mouse brain lysates and further demonstrated reduced levels of nitric oxide (NO) typical of the human immune response on injection with lipopolysaccharide (LPS). HuNOS2 tg /mNos2 -/- brain samples were probed for characteristic differences in redox and immune gene profiles compared to WT mice using gene arrays. Selected genes were also compared against mNos2 -/- brain lysates. Reconstitution of the human NOS2 gene significantly altered genes that encode multiple anti-oxidant proteins, oxidases, DNA repair, mitochondrial proteins and redox regulated immune proteins. Expression levels of typical pro-inflammatory, anti-inflammatory and chemokine genes were not significantly different with the exception of increased TNFα and Ccr1 mRNA expression in the HuNOS2 tg /mNos2 -/- mice compared to WT or mNos2 -/- mice. NO is a principle factor in establishing the tissue redox environment and changes in NO levels impact oxidative stress and immunity, both of which are primary characteristics of neurodegenerative diseases. The HuNOS2 tg /mNos2 -/- mice provide a potentially useful mechanism to address critical species- specific immune differences that can impact the study of human diseases.
- 17 November 2014
- Published by Springer Nature in Molecular Neurodegeneration
- Vol. 9 (1) , 50
Open AccessThe impact of human and mouse differences in NOS2 gene expression on the brain’s redox and immune environment
Mouse models are used in the study of human disease. Despite well-known homologies, the difference in immune response between mice and humans impacts the application of data derived from mice to human disease outcomes. Nitric oxide synthase-2 (NOS2) is a key gene that displays species-specific outcomes via altered regulation of the gene promoter and via post-transcriptional mechanisms in humans that are not found in mice. The resulting levels of NO produced by activation of human NOS2 are different from the levels of NO produced by mouse Nos2. Since both tissue redox environment and immune responsiveness are regulated by the level of NO and its interactions, we investigated the significance of mouse and human differences on brain oxidative stress and on immune activation in HuNOS2 tg /mNos2 -/- mice that express the entire human NOS2 gene and that lack a functional mNos2 compared to wild type (WT) mice that express normal mNos2. Similarly to human, brain tissue from HuNOS2 tg /mNos2 -/- mice showed the presence of a NOS2 gene 3′UTR binding site. We also identified miRNA-939, the binding partner for this site, in mouse brain lysates and further demonstrated reduced levels of nitric oxide (NO) typical of the human immune response on injection with lipopolysaccharide (LPS). HuNOS2 tg /mNos2 -/- brain samples were probed for characteristic differences in redox and immune gene profiles compared to WT mice using gene arrays. Selected genes were also compared against mNos2 -/- brain lysates. Reconstitution of the human NOS2 gene significantly altered genes that encode multiple anti-oxidant proteins, oxidases, DNA repair, mitochondrial proteins and redox regulated immune proteins. Expression levels of typical pro-inflammatory, anti-inflammatory and chemokine genes were not significantly different with the exception of increased TNFα and Ccr1 mRNA expression in the HuNOS2 tg /mNos2 -/- mice compared to WT or mNos2 -/- mice. NO is a principle factor in establishing the tissue redox environment and changes in NO levels impact oxidative stress and immunity, both of which are primary characteristics of neurodegenerative diseases. The HuNOS2 tg /mNos2 -/- mice provide a potentially useful mechanism to address critical species- specific immune differences that can impact the study of human diseases.