Fig. 4. Creation of a Sim1 allele expressing Tau-lacZ. (A) Schematic representation of the Sim1 locus (wt), of the targeting vector (HR), and of the Sim1 mutant allele (m). Homologous recombination replaces the initiation codon and the basic HLH domain with a Tau-lacZ fusion gene. The 5' external probe is indicated. B, BamHI; H, HindIII. (B) Southern blot analysis of genomic DNA from Sim1^+/+, Sim1^tlz/+ and Sim1^tlz/tlz mice. The 5' probe detects a wild-type 5.2-kb BamHI fragment and a mutant 4.5-kb BamHI fragment. (C,D) Sagittal sections through the MB of Sim1^+/+;Sim2^+/+ and Sim1^tlz/tlz;Sim2^-/- E18.5 embryos that have been stained with Haematoxylin. The MTT and the PMT are not detectable in the MB of embryos homozygous for the Sim1^- (C) or the Sim1^tlz (D) allele.