Generation and characterization of mouse models expressing wild-type human GP Ibα (hTg^WT) and a truncated form of GP Ibα (hTg^Y605X). (A) Animal models have been developed lacking the murine GP Ibα genes and expressing normal human GP Ibα (hTg^WT) and a truncated human GP Ibα variant (hTg^Y605X). Both expressed human transgenes were driven by megakaryocytic-specific promoters. (B) Shown are the primary sequence alignments for the cytoplasmic tails of mouse (Mo) and human (Hu) GP Ibα. *The amino acid position (605) where a Tyr605 codon was replaced with a stop codon to truncate the cytoplasmic tail of GP Ibα. (C) Flow cytometry profiles of platelets in whole blood are shown using blood from hTg^WT and hTg^Y605X animals. Fluorescence was produced using an FITC-labeled anti–human GP Ibα monoclonal antibody, LJ-P3. The negative control (dotted line) was fluorescence produced by nontransgenic or normal mice. (D) von Willebrand factor binding isotherms are shown for washed platelets from hTg^WT and hTg^Y605X blood. (E) Mouse platelet lysates were immunoprecipitated with LJ-P3 and immunoblotted with an antifilamin-1 polyclonal antibody and an anti–GP Ibα polyclonal antibody.