Proper development of the anterior segment of the mammalian eye is critical for normal ocular function. Indeed, several congenital syndromes associated with anterior segment anomalies can lead to impaired vision and glaucoma. One such syndrome is nail patella syndrome (NPS), caused by haploinsufficiency for the LIM-homeodomain transcription factor LMX1B. Although mutations in LMX1B cosegregate with NPS, whether these mutations cause the glaucoma associated with NPS is not known. Here, we provide evidence that the LIM-homeodomain transcription factor lmx1b is an essential regulator of murine anterior segment development. Mice that are homozygous for a targeted mutation of lmx1b display iris and ciliary body hypoplasia, and cornea stromal defects. In addition, two cDNAs normally downregulated in presumptive cornea, mf1 and mfh1, exhibit persistent expression, while keratocan, a keratin sulfate proteoglycan expressed by keratocytes, is not detected in mutant corneas. Moreover, ultrastructural examination of homozygous mutants indicates that corneal collagen fibrillogenesis is perturbed. Taken together, our studies suggest a developmental etiology for glaucoma in NPS patients and highlight lmx1b as an essential regulator of anterior segment morphogenesis and patterning. genesis 26:15-25, 2000.
Copyright 2000 Wiley-Liss, Inc.