Targeted disruption of Ins1 and Ins2. Structures of the targeting vectors as well as of the wild-type (wt) and recombinant alleles are shown in A for Ins1 and in B for Ins2. The restriction enzymes and probes used for genotyping of cellular and mouse DNAs are indicated. Autoradiograms of Southern blot analyses confirming the presence of ES cells (D3) carrying recombined alleles for Ins1 (D3R1) or Ins2 (D3R2) and shown in C and of Ins1−/−, Ins2−/− and double homozygous mutant mice are shown in D. neo, Neomycin phosphotransferase gene; tk, thymidine kinase gene from herpes simplex virus type 1; B, BamHI; E, EcoRI; H, HindIII; N, NsiI; P, PvuII; X, XbaI.