Lmx1b, a LIM homeodomain class transcription factor, is necessary for normal development of multiple tissues in the anterior segment of the murine eye

Proper development of the anterior segment of the mammalian eye is critical for normal ocular function. Indeed, several congenital syndromes associate d with anterior segment anomalies can lead to impaired vision and glaucoma, One such syndrome is nail patella syndrome (NPS), caused by haploinsuffici ency 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-ho meodomain transcription factor lmx1b is an essential regulator of murine an terior segment development. Mice that are homozygous for a targeted mutatio n of lmx1b display iris and ciliary body hypoplasia, and cornea stromal def ects. In addition, two cDNAs normally downregulated in presumptive cornea, mf1 and mfh1, exhibit persistent expression, while keratocan, a keratin sul fate proteoglycan expressed by keratocytes, is not detected in mutant corne as, Moreover, ultrastructural examination of homozygous mutants indicates t hat corneal collagen fibrillogenesis is perturbed, Taken together, our stud ies suggest a developmental etiology for glaucoma in NPS patients and highl ight lmx1b as an essential regulator of anterior segment morphogenesis and patterning. (C) 2000 Wiley-Liss, Inc.