PMID- 22474370
OWN - NLM
STAT- MEDLINE
DCOM- 20120712
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 16
DP  - 2012 Apr 17
TI  - Mouse model recapitulating human Fcgamma receptor structural and functional 
      diversity.
PG  - 6181-6
LID - 10.1073/pnas.1203954109 [doi]
AB  - The in vivo biological activities of IgG antibodies result from their 
      bifunctional nature, in which antigen recognition by the Fab is coupled to the 
      effector and immunomodulatory diversity found in the Fc domain. This diversity, 
      resulting from both amino acid and glycan heterogeneity, is translated into 
      cellular responses through Fcgamma receptors (FcgammaRs), a structurally and functionally 
      diverse family of cell surface receptors found throughout the immune system. 
      Although many of the overall features of this system are maintained throughout 
      mammalian evolution, species diversity has precluded direct analysis of human 
      antibodies in animal species, and, thus, detailed investigations into the unique 
      features of the human IgG antibodies and their FcgammaRs have been limited. We now 
      report the development of a mouse model in which all murine FcgammaRs have been 
      deleted and human FcgammaRs, encoded as transgenes, have been inserted into the mouse 
      genome resulting in recapitulation of the unique profile of human FcgammaR 
      expression. These human FcgammaRs are shown to function to mediate the 
      immunomodulatory, inflammatory, and cytotoxic activities of human IgG antibodies 
      and Fc engineered variants and provide a platform for the detailed mechanistic 
      analysis of therapeutic and pathogenic IgG antibodies.
FAU - Smith, Patrick
AU  - Smith P
AD  - Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New 
      York, NY 10021, USA.
FAU - DiLillo, David J
AU  - DiLillo DJ
FAU - Bournazos, Stylianos
AU  - Bournazos S
FAU - Li, Fubin
AU  - Li F
FAU - Ravetch, Jeffrey V
AU  - Ravetch JV
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120402
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/immunology
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism
MH  - Cells, Cultured
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Female
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Genetic Variation/*immunology
MH  - Humans
MH  - Immunoglobulin G/genetics/*immunology/metabolism
MH  - Lung Neoplasms/genetics/immunology/secondary
MH  - Male
MH  - Melanoma, Experimental/genetics/immunology/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Protein Isoforms/genetics/immunology/metabolism
MH  - Receptors, IgG/genetics/*immunology/metabolism
PMC - PMC3341029
COIS- The authors declare no conflict of interest.
EDAT- 2012/04/05 06:00
MHDA- 2012/07/13 06:00
PMCR- 2012/10/17
CRDT- 2012/04/05 06:00
PHST- 2012/04/05 06:00 [entrez]
PHST- 2012/04/05 06:00 [pubmed]
PHST- 2012/07/13 06:00 [medline]
PHST- 2012/10/17 00:00 [pmc-release]
AID - 1203954109 [pii]
AID - 201203954 [pii]
AID - 10.1073/pnas.1203954109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6181-6. doi: 
      10.1073/pnas.1203954109. Epub 2012 Apr 2.