(A) Targeting strategy and conditional disruption. Closed boxes, exons; ATG, translation start site; bHLH, exon encoding basic helix-loop-helix domain; NEO, neomycin resistance marker; DT, diphtheria toxin cassette; triangles, loxP sites; ovals, Frt sites; bars with kilobase (kb) markers, sites and sizes of PCR products diagnostic of genotypes. (B) PCR products amplified from mouse tail DNA demonstrating the indicated genotypes. +, wildtype allele; KO, disrupted allele (from ubiquitously-acting Cre); flox, conditional allele. (C) Functional validation of Bmal1 condition allele: conditional loss of circadian rhythms of locomotor activity. Shown are representative double-plotted records of running-wheel activity in DD of mice homozygous for the conditional Bmal1 allele with or without a ubiquitously-acting Cre. Tick mark heights correspond to the number of running-wheel revolutions in a 6-min bin.