Mice lacking c-Src form multinucleated OCs but develop osteopetrosis due to defects in ruffled border formation and bone resorption.184,185 Mechanistically, SHP1 and SHP2 regulate c-Src activation by promoting c-Src Y416 phosphorylation77 or by dephosphorylating the inhibitory Y527 of c-Src.186. This evidence concerns the gene SRC and osteopetrosis.