Primary defects in the lens underlie complex anterior segment abnormalities of the Pax6 heterozygous eye

We describe lens defects in heterozygous small eye mice, and autonomous deficiencies of Pax6(+/−) cells in the developing lens of Pax6(+/+) ↔ Pax6(+/−) chimeras. Two separate defects of the lens were identified by analyzing the distribution of heterozygous cells in chimeras: Pax6(+/−) cells are less readily incorporated into the lens placode than wild type, and those that are incorporated into the lens are not maintained efficiently in the proliferating lens epithelium. The lens of chimeric eyes is, therefore, predominantly wild type from embryonic day 16.5 onwards, whereas heterozygous cells contribute normally to all other eye tissues. Eye size and defects of the iris and cornea are corrected in fetal and adult chimeras with up to 80% mutant cells. Therefore, these aspects of the phenotype may be secondary consequences of primary defects in the lens, which has clinical relevance for the human aniridia (PAX6(+/−)) phenotype.