Fig. 1. Schematic drawings of the Pax6 mRNA in wild type (WT) and mice harboring mutations in the distinct DNA-binding domains of Pax6. (A) The mRNA of Pax6 consists of two DNA binding-domains, the paired domain (PD) and the homeodomain (HD). The PD is subdivided in two independent DNA-binding domains, the N-terminal PAI and the C-terminal RED domain. The PAI domain is able to bind to P6CON (Pax6 consensus site) and 5aCON (Pax6(5a) consensus site), whereas the RED domain binds exclusively to 5aCON. By means of alternative splicing, 14 amino acids are inserted into the N-terminal PAI domain (see yellow box) and thereby abolish its DNA binding. The transactivation domain (TA), important for gene activation, is located at the C-terminal end of Pax6. (B) The Pax6^Aey18 mutant is characterized by a large deletion in the PD (exon 5a and exon 6), whereas the HD and TA are still present. (C) The Pax6(5a)–/– lacks exon 5a in the PD due to gene targeting (Singh et al., 2002), while the rest of the PD, HD and TA are unaffected. (D) Pax6^4Neu mutant mice bear a point mutation in the HD that abolishes DNA binding of the HD, while PD and TA are intact (Favor et al., 2001). (E) The Pax6^Sey mutant mice are characterized by a truncated form of Pax6, lacking the HD and TA. These mutants have a comparable phenotype to the full gene deletion (Pax6–/–) and are therefore referred to as functional null alleles. PD, paired domain; HD, homeodomain; TA, PST-rich transactivator domain.