Pleckstrin targeting. (A) Recombination into the pleckstrin gene results in the deletion of the nucleotides corresponding to amino acids 76 through 128 encoded within exon 3. This removes the distal portion of a β sheet, and the critical α helix from the first PH domain. (B) Southern blotting of mouse genomic DNA. Southern blotting shows a 2.8-kb wild-type band, and a 2.4-kb targeted band. (C) PCR of genomic DNA with a sense primer homologous to a region 5′ of the targeted region and antisense primers homologous to either HPRT or exon 3 of the pleckstrin gene. (D) Antipleckstrin immunoblot of platelet lysates showing complete loss of pleckstrin protein in mice homozygous for the recombinant gene. (E) The mean and SD of platelet counts derived from 8 pleckstrin-null mice and 8 wild-type littermates are shown.