Targeted Mutation of Nuclear Bone Morphogenetic Protein 2 Impairs Secondary Immune Response in a Mouse Model

Daniel S Olsen; Wesley A Goar; Brandt A Nichols; K Tyson Bailey; S Loyd Christensen; Kayla R Merriam; Paul R Reynolds; Eric Wilson; K Scott Weber; Laura C Bridgewater

doi:10.1155/2015/975789

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Targeted Mutation of Nuclear Bone Morphogenetic Protein 2 Impairs Secondary Immune Response in a Mouse Model

Journal article

Open access

Peer reviewed

Targeted Mutation of Nuclear Bone Morphogenetic Protein 2 Impairs Secondary Immune Response in a Mouse Model

Daniel S Olsen, Wesley A Goar, Brandt A Nichols, K Tyson Bailey, S Loyd Christensen, Kayla R Merriam, Paul R Reynolds, Eric Wilson, K Scott Weber and Laura C Bridgewater

BioMed research international, Vol.2015, 975789

2015

DOI: 10.1155/2015/975789

PMCID: PMC4603606

PMID: 26491697

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https://doi.org/10.1155/2015/975789View

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Abstract

We recently identified a nuclear variant of the BMP2 growth factor, called nBMP2. In an effort to understand the function of this variant protein, we generated a mouse line in which BMP2 is expressed and functions normally, but nBMP2 is excluded from the nucleus. This novel mutation allows the study of nBMP2 without compromising BMP2 function. To determine whether nBMP2 plays a role in immune function, we performed a series of experiments in which we compared mouse survival, organ weights, immune cells numbers, and bacterial load in wild type and nBmp2NLS(tm) mice following primary and secondary challenges with Staphylococcus aureus. Following primary challenge with S. aureus, wild type and nBmp2NLS(tm) mice showed no differences in survival or bacterial load and generated similar numbers and types of leukocytes, although mutant spleens were smaller than wild type. Secondary bacterial challenge with S. aureus, however, produced differences in survival, with increased mortality seen in nBmp2NLS(tm) mice. This increased mortality corresponded to higher levels of bacteremia in nBmp2NLS(tm) mice and to a reduced enlargement of mutant spleens in response to the secondary infection. Together, these results suggest that the recently described nuclear variant of BMP2 is necessary for efficient secondary immune responses.

Mutation

Bone Morphogenetic Protein 2 - genetics

Staphylococcal Infections - genetics

Staphylococcal Infections - immunology

Staphylococcal Infections - pathology

Humans

Nuclear Proteins - immunology

Animals

Mice, Mutant Strains

Bone Morphogenetic Protein 2 - immunology

Staphylococcus aureus - immunology

Mice

Nuclear Proteins - genetics

Details

Title: Subtitle: Targeted Mutation of Nuclear Bone Morphogenetic Protein 2 Impairs Secondary Immune Response in a Mouse Model
Creators: Daniel S Olsen - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
Wesley A Goar - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
Brandt A Nichols - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
K Tyson Bailey - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
S Loyd Christensen - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
Kayla R Merriam - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
Paul R Reynolds - Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA
Eric Wilson - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
K Scott Weber - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
Laura C Bridgewater - Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA
Resource Type: Journal article
Publication Details: BioMed research international, Vol.2015, 975789
DOI: 10.1155/2015/975789
PMID: 26491697
PMCID: PMC4603606
NLM abbreviation: Biomed Res Int
ISSN: 2314-6133
eISSN: 2314-6141
Publisher: United States
Grant note: T32 GM008629 / NIGMS NIH HHS
Language: English
Date published: 2015
Academic Unit: Microbiology and Immunology; Infectious Diseases; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984025450202771

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