|ZFIN ID: ZDB-PERS-030912-8|
BIOGRAPHY AND RESEARCH INTERESTS
My project centers on the ocular function of two specific zebrafish genes known to be mutated in human glaucoma: lmx1b and myocilin. Lmx1b is a LIM homeodomain transcription factor and loss-of-function mutations in lmx1b have been shown to cause juvenile-onset open angle glaucoma. To test the role of lmx1b mutations, I plan to design morpholinos to knock-down lmx1b function in zebrafish embryos. Embryos without lmx1b will be assessed for gross abnormalities and development of the ocular anterior segment. Myocilin is a large glycoprotein with unknown function. Gain-of-function mutations in this gene also results in juvenile-onset open angle glaucoma. Because glaucoma-causing mutations in myocilin are thought to be gain-of-function, I will investigate the consequences of over-expressing the disease form of myocilin in transgenic zebrafish. Adult transgenic fish will then be assessed for glaucoma phenotypes such as elevated intraocular pressure and retinal ganglion cell loss.
McMahon, C., Gestri, G., Wilson, S.W., and Link, B.A. (2009) Lmx1b is essential for survival of periocular mesenchymal cells and influences Fgf-mediated retinal patterning in zebrafish. Developmental Biology. 332(2):287-298
McMahon, C., Semina, E.V., and Link, B.A. (2004) Using zebrafish to study the complex genetics of glaucoma. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 138(3):343-350