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Figure 1


Fig. 1. (A) Generation of floxed/deleted Gata3 alleles. LoxP sites were introduced in the start codon (in exon 2) and in the second intron (blue flags) of Gata3. A Puro cassette, flanked by FRT sites (pink flags) and coupled to an nlsLacZ gene lacking a polyA signal was introduced in intron 2. Arrows indicate lengths of NotI-SalI restriction enzyme fragments that hybridize to the external 5' probe. A Polyoma thymidine kinase gene (PyTK) was added 5' to the construct to counter select against random integration. Flp recombinase mice (Buchholz et al., 1998) were used to remove the Puro cassette. After recombination by Cre recombinase, resulting in excision of the part of exon 2 that is 3' to the start ATG of Gata3 and the part of intron 2 that is 5' to the EcoRI site, the nlsLacZ reporter replaces the 3' end of the truncated Gata3 gene. Arrows below genes indicate direction of transcription. Black boxes correspond to exons. B, BamHI; C, ClaI; H, HindIII; N, NcoI; R, EcoRI; S, SacI. (B-T). Phenotypes caused by homozygous deletion of Gata3 in the skin (ko) versus wt. (B) Delayed hair growth in K14-Gata3-/- at P10. (C) Short stubby hairs instead of normal coat of fur. (D) Weight difference in the first months of life. (E,F) Eyes are still closed, whiskers are present but rudimentary, most facial hairs have disappeared and remaining hairs are still very short. (G) After 3 months, most K14-Gata3-/- mice are completely bald; eyes are still closed. (H,I) The absence of visible nipples in female K14-Gata3-/- mice. (J,K) The complete loss of hairs from the abdominal area at 2 months. (L,M) Baldness starts at the head and progress from anterior to posterior. (N-P) Coat of fur at P26. d, dorsal; v, ventral. (N) wt back hair; (O) K14-Gata3-/- back hair; (P) K14-Gata3-/- belly hair (and flakes; note the encircled, thick rounded tip of the hair instead of the normal fine hair tips). (Q,R) Scanning electron microscopy of dorsal wt (Q) and K14-Gata3-/- (R) hairs of 12-week-old mice. Note thickness of K14-Gata3-/- hair as well as absence of regular cuticle cells and presence of irregular flakes. (S,T) Around P24, K14-Gata3-/- skin starts flaking. Scale bar in Q: 50 µm for Q,R.





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