ena-STUDY-WASHINGTON UNIVERSITY  SCHOOL OF MEDICINE-30-11-2017-16:37:09:180-112
LysMD3 is a type II membrane protein without an in vivo role in the response to a range of pathogens
Germline-encoded receptors recognizing common pathogen-associated molecular patterns are a central element of the innate immune system and play an important role in shaping the host response to infection. Many of the innate immune molecules central to these signaling pathways are evolutionarily conserved, from flies to mice and humans. LysMD3 is a novel molecule containing a putative peptidoglycan-binding domain that has orthologs in humans, mice, zebrafish, worms, and flies. We found that the LysM of LysMD3 forms a folded structure and is likely related to a previously described PGN-binding LysM found in bacteria. Mouse LysMD3 is a type II integral membrane protein that co-localizes with GM130+ structures, consistent with localization to the cis-Golgi. We describe here two lines of mLysMD3-deficient mice for in vivo characterization of mLysMD3 function. We found that mLysMD3-deficient mice were born at Mendelian ratios and had no obvious pathologic abnormalities. They also had no obvious immune response deficiencies in a number of models of infection and inflammation. mLysMD3-deficient mice exhibited no signs of dysbiosis by 16S analysis or altered intestinal gene expression by RNA-Seq. We conclude that mLysMD3 contains a LysM motif with cytoplasmic orientation, but were unable to define a physiologic role for the molecule in vivo.
Germline-encoded receptors recognizing common pathogen-associated molecular patterns are a central element of the innate immune system and play an important role in shaping the host response to infection. Many of the innate immune molecules central to these signaling pathways are evolutionarily conserved, from flies to mice and humans. LysMD3 is a novel molecule containing a putative peptidoglycan-binding domain that has orthologs in humans, mice, zebrafish, worms, and flies. We found that the LysM of LysMD3 forms a folded structure and is likely related to a previously described PGN-binding LysM found in bacteria. Mouse LysMD3 is a type II integral membrane protein that co-localizes with GM130+ structures, consistent with localization to the cis-Golgi. We describe here two lines of mLysMD3-deficient mice for in vivo characterization of mLysMD3 function. We found that mLysMD3-deficient mice were born at Mendelian ratios and had no obvious pathologic abnormalities. They also had no obvious immune response deficiencies in a number of models of infection and inflammation. mLysMD3-deficient mice exhibited no signs of dysbiosis by 16S analysis or altered intestinal gene expression by RNA-Seq. We conclude that mLysMD3 contains a LysM motif with cytoplasmic orientation, but were unable to define a physiologic role for the molecule in vivo.