Gene targeted disruption of the Tmprss6 gene. (A) Partial genomic structure of the murine Tmprss6 gene (top). Exon coding sequences are indicated as black bars. The targeting vector duplicates exons III to VI (bottom). E indicates EcoRI; S, SspI; N, NdeI; 3′Hprt, 3′-half Hprt minigene; Puro, puromycin resistance gene; Ag, K14 Agouti minigene. (B) Predicted structure of the targeted allele. (C) Southern blot analysis of DNA from Tmprss6+/+, Tmprss6+/−, and Tmprss6−/− mice digested with SspI. Hybridization with the 3′-external probe detects the expected 33-kb and 9-kb bands corresponding to wild-type and mutant alleles, respectively. (D) Northern blot analysis of liver tissues obtained from wild-type and Tmprss6−/− mice showing the absence of full-length Tmprss6 mRNA expression in mutant mice.