Deletion of the chop gene. (A) Structure of wild-type and mutant chop alleles. Exons are boxed, the coding region is shaded. In the targeted allele the chop-coding region, between the PmlI and the NheI sites is replaced by a PGK.neo gene (Apa–ApaI, X-XhoI, Bgl–BglII, P–PmlI, Nhe–NheI, Xba–XbaI). (Inset) An autoradiograph of a Southern blot of BglII-digested genomic DNA hybridized with a 3′ probe that is external to the targeting construct and detects both the wild-type and mutant chop alleles. (B) Northern blot analysis of CHOP, BiP, and tubulin in tunicamycin-treated (1 μg/ml for 6 hr) MEFs with the indicated chop genotypes. Note the absence of CHOP mRNA and the normal BiP induction in the chop −/− cells.