Mutation in the Bmpr1b gene affects optic nerve development

• Published in: Acta ophthalmologica (Oxford, England) Vol. 88; no. s246
• Main Authors: GRAW, J, WEBER, S, PUK, O, WAGNER, S, KLAFTEN, M, THIELE, F, FUCHS, H, HRABé DE ANGELIS, M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2010
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2010.2344.x

Purpose Systematic analysis of the ocular defects in a new mouse mutant carrying a Bmpr1b mutation.
Methods The Bmpr1b mutants were analyzed by slit lamp, funduscopy, laser interference biometry, electroretinography, virtual drum, histology and in‐situ hybridization.
Results The new Bmpr1b mutant is characterized by a T‐>G transversion in the splice donor site of exon 10. The mutants show irregular forelimb and hindlimb morphology, brachydactyly, irregular cartilage development and alterations in the reproductive system. The lens is clear, but in homozygous mutants, an enlarged optic disc was observed by funduscopy. The eyes are slightly larger, which is mainly due to an increased aqueous humor. Electroretinography demonstrated a more rapid decline of the b‐wave indicating a less efficient transmission of electric stimuli within the retina. Moreover, homozygous mutant mice show also almost no response to moving stripes as compared to the wild type mice. Histological analysis indicated dramatic changes in the optic nerve head. Analysis of the embryonic development of the eye showed that the expression area of Pax6 expands posterior, and concomitantly, Pax2 expression (which is regular at embryonic day 11.5) is repressed at embryonic days 15.5 and 17.5 at the optic nerve head.
Conclusion The T‐G mutation in the splice donor site of exon 10 of the Bmpr1b gene leads to a recessive hypoplasia of the optic nerve head, which is mainly caused by repression of Pax2 expression in the late phase of embryogenesis.