Targeted Mutation of Nuclear Bone Morphogenetic Protein 2 Impairs Secondary Immune Response in a Mouse Model.
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.
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Daniel S
DS
Olsen
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Wesley A
WA
Goar
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Brandt A
BA
Nichols
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
K Tyson
KT
Bailey
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
S Loyd
SL
Christensen
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Kayla R
KR
Merriam
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
Paul R
PR
Reynolds
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Eric
E
Wilson
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
K Scott
KS
Weber
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Laura C
LC
Bridgewater
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D009687:Nuclear Proteins