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    A RANKL G278R mutation causing osteopetrosis identifies a functional amino acid essential for trimer assembly in RANKL and TNF.

    Using EMU-generated random mutations, the authors generated a mouse with a novel glycine to arginine mutation of codon 278 (G278R) in RANKL.  These mice develop severe osteopetrosis similar to Rankl-deficient mice and administration of recombinant RANKL restored osteoclast formation in vivo. The authors demonstrate that RANKLG278R monomers fail to assemble into homotrimers, are unable to bind and activate the RANK receptor and interact with wild-type RANKL, exerting a dominant-negative effect on its trimerization and function in vitro.

    http://hmg.oxfordjournals.org/content/early/2011/11/16/hmg.ddr510.long

    Douni E, Rinotas V, Makrinou E, Zwerina J, Penninger JM, Eliopoulos E, et al