FIGURE 1. Tamoxifen-induced RXR null mutation in adult mouse epidermis mediated by Cre–ER^T.

a, Diagram of the wild-type RXR genomic locus (+), the floxed RXR L2 allele, the RXR L- allele obtained after Cre-mediated excision of exon 4 (encoding the DNA-binding domain), and the RXR null allele (-)¹⁶. Black boxes indicate exons (E2–E4). Restriction enzyme sites and probe X4 location are indicated. BamHI fragments are in kilobases (kb). B, BamHI; C, ClaI; E, EcoRI; H, HindIII, S, SpeI; X, XbaI. Arrowheads in L2 and L- alleles indicate LoxP sites. b, Tamoxifen (Tam)-induced generation of K5–Cre–ER ^T-mediated RXR^L- alleles illustrated by Southern blot analysis of epidermal DNA isolated 6 (lanes 1–3) and 12 (lanes 4–6) weeks after the first Tam (1 mg) injection series (AFT). All mice were K5–Cre–ER^T(tg/0) and the RXR genotypes are indicated. BamHI-digested DNA fragments corresponding to RXR (+), L2, L- and (-) alleles are displayed. c, Tissue-specificity of Cre-ER^T-mediated RXR disruption. WT (+), L2 and L- alleles were identified by PCR on DNA extracted from various organs of K5–Cre–ER ^T(tg/0)/RXR^L2/+ mice, 12 weeks AFT. d, Tamoxifen-induced generation of RXR null alleles in adult mouse epidermis using K14–Cre–ER^T2(tg/0)or K14–Cre–ER ^T2(0/0) mice (designated (tg/0) and (0/0), respectively). PCR analysis of genomic DNA from epidermis (E) and dermis (D), isolated two weeks after injection of either Tam (0.1 mg) (+) or vehicle (-). Mouse genotypes are indicated and PCR fragments corresponding to RXR (+), L2 and L- alleles are displayed.