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The Tyr423His point mutation, corresponding to the severe glaucoma-causing Tyr437His mutation in the human<jats:italic>MYOC<\/jats:italic>gene, was introduced into bacterial artificial chromosome DNA encoding the full-length mouse<jats:italic>Myoc<\/jats:italic>gene and long flanking regions. Both wild-type (Wt) and Tg animals expressed Myoc in tissues of the irido-corneal angle and the sclera. Expression of mutated Myoc induced the accumulation of Myoc in cell cytoplasm and prevented its secretion into the extracellular space. The levels of ATPase-1 were reduced in the irido-corneal angle of Tg mice compared with Wt animals. Tg mice demonstrated a moderate elevation of intraocular pressure, the loss of \u223c20% of the retinal ganglion cells (RGCs) in the peripheral retina, and axonal degeneration in the optic nerve. RGC depletion was associated with the shrinkage of their nuclei and DNA fragmentation in the peripheral retina. Pathological changes observed in the eyes of Tg mice are similar to those observed in glaucoma patients.<\/jats:p>","DOI":"10.1523\/jneurosci.3020-06.2006","type":"journal-article","created":{"date-parts":[[2006,11,16]],"date-time":"2006-11-16T02:56:35Z","timestamp":1163645795000},"page":"11903-11914","source":"Crossref","is-referenced-by-count":124,"title":["Expression of Mutated Mouse Myocilin Induces Open-Angle Glaucoma in Transgenic Mice"],"prefix":"10.1523","volume":"26","author":[{"given":"Vladimir","family":"Senatorov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Malyukova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Fariss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric 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