This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Myocilin in microarrays
While myocilin's normal function is still not clearly defined, microarray experiments have been completed to see how myocilin's expression affects other proteins, both ocular and non-ocular proteins. Below is a compilation of three microarray datasets on myocilin that I found most interesting along with a brief summary of what I found as information gained about myocilin in these studies.
Elevated amounts of myocilin in the aqueous humor of transgenic mice cause significant changes in ocular gene expression by Walter Paper, et al (2008). To read the full article, click HERE.
To assess the effects of elevated amounts of myocilin on aqueous humor outflow dynamics in an in vivo system, transgenic βB1-crystallin-MYOC mice that strongly overexpress myocilin in their eyes were created. The transgenic overexpression of myocilin results in an almost five-fold increase of secreted normal myocilin in the aqueous humor of βB1-crystallin-MYOC mice. In addition, several genes that encode for olfactomedin proteins showed distinct changes in expression. Olfml3 was significantly downregulated, while Lphn1, Lphn2, and Lphn3 were significantly upregulated. Our findings support a role for myocilin in modulating cellular adhesion, and suggest functional processes that involve other proteins of the olfactomedin family.
Figure 8 from Paper et al. article below: Real time RT-PCR analysis for the differential expression of the mRNA of various olfactomedin proteins in RNA from βB1-crystallin-MYOC mice (overexpressing myocilin) and wild-type littermates. Means ± standard deviation of four independent experiments run in duplicate are shown. The mean value obtained with RNA from wild-type animals was set at 1. Asterisks mark statistical significant differences between βB1-crystallin-MYOC mice and wild-type littermates (p < 0.05 for * and p <0.02 for **).
Citation: Walter Paper, Markus Kroeber, Sebastian Heersink, Dietrich A. Stephan, Rudolf Fuchshofer, Paul Russell, and Ernst R. TammExp Eye Res. Elevated amounts of myocilin in the aqueous humor of transgenic mice cause significant changes in ocular gene expression. Author manuscript; available in PMC 2009 September 1.PMCID: PMC2572563Published in final edited form as: Exp Eye Res. 2008 September; 87(3): 257–267. Published online 2008 June 17. doi: 10.1016/j.exer.2008.06.006.
Overexpression of Myocilin in the Drosophila Eye Activates the Unfolded Protein Response: Implications for Glaucoma by Mary Anna Carbone et al (2009). To read the full article, click HERE.
Aggregation of MYOC in the endoplasmic reticulum activates the UPR, a stress pathway that culminates in apoptosis. Using Drosophila, they found that MYOC-associated ocular hypertension in the human eye may result from aggregation of MYOC and induction of the UPR in trabecular meshwork cells. This process could occur at a late age with wild-type MYOC, but might be accelerated by MYOC mutants to account for juvenile onset glaucoma.
Citation: Carbone MA, Ayroles JF, Yamamoto A, Morozova TV, West SA, et al. (2009) Overexpression of Myocilin in the Drosophila Eye Activates the Unfolded Protein Response: Implications for Glaucoma. PLoS ONE 4(1): e4216. doi:10.1371/journal.pone.0004216
Altered expression of myocilin in the brain of a mouse model for phenylketonuria (PKU) by Sankar Surendran et al (2005). To read the full article, click HERE.
An expression analysis was performed in the brain of a mouse model for PKU. Microarray expression profile of the brain showed lower expression of myocilin (Myoc) in the PKU mouse. Reduced expression of Myoc was further confirmed by one-step real-time RT-PCR. Western blotting analysis of the brain using equal quantities of protein showed a thin band in PKU compared to a prominent band in the wild type brain.
Citation: Surendran S., Matalon D., Tyring S.K., Rady P.L., Velagaleti G.V., Matalon R. Altered expression of myocilin in the brain of a mouse model for phenylketonuria (PKU) (2005) Neuroscience Letters, 382 (3), pp. 323-326.
An expression analysis was performed in the brain of a mouse model for PKU. Microarray expression profile of the brain showed lower expression of myocilin (Myoc) in the PKU mouse. Reduced expression of Myoc was further confirmed by one-step real-time RT-PCR. Western blotting analysis of the brain using equal quantities of protein showed a thin band in PKU compared to a prominent band in the wild type brain.
Citation: Surendran S., Matalon D., Tyring S.K., Rady P.L., Velagaleti G.V., Matalon R. Altered expression of myocilin in the brain of a mouse model for phenylketonuria (PKU) (2005) Neuroscience Letters, 382 (3), pp. 323-326.
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References:
1. Fuse, Nobuo. "Genetic Bases for Glaucoma." The Tohoku Journal of Experimental Medicine 221 (2010): 1-10. PubMed. Web. 22 Jan. 2011
http://www.jstage.jst.go.jp/article/tjem/221/1/1/_pdf
2. Rao, Kollu N., Srujana Nagireddy, and Subhabrata Chakrabarti. "Complex Genetic Mechanisms in Glaucoma: An Overview." Indian Journal of Opthamology 59.7 (2011): 31-42. PubMed. Web. 22 Jan. 2011.
http://www.ijo.in/article.asp?issn=0301-4738;year=2011;volume=59;issue=7;spage=31;epage=42;aulast=Rao
3. American Optometric Association. Answers To Your Questions About Glaucoma. St. Louis: American Optometric Association. Print.
4. http://www.forbes.com/2009/06/26/life-saving-devices-technology-personal-monitors_slide_7.html
5. http://www.youtube.com/watch?v=OJMEfGFbFMI
6. "MYOC - Myocilin, Trabecular Meshwork Inducible Glucocorticoid Response - Genetics Home Reference." Genetics Home Reference - Your Guide to Understanding Genetic Conditions. 6 Feb. 2011. Web. 08 Feb. 2011. http://ghr.nlm.nih.gov/gene/MYOC
7. Saura, Maria, Montse Cabana, Carmen Ayuso, and Diana Valverde. "European Journal of Human Genetics - Mutations including the Promoter Region of Myocilin//TIGR Gene." Nature Publishing Group : Science Journals, Jobs, and Information. 13 Oct. 2004. Web. 08 Feb. 2011. http://www.nature.com/ejhg/journal/v13/n3/full/5201299a.html
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9. McMahon, C., Semina, E.V., Link, B.A. "Using zebrafish to study the complex genetics of glaucoma." Comparative Biochemistry and Physiology Part C: Toxicology and Parmacology. vol 138-3. July 2004. Web. 24 Feb 2011. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W89-4CDJG6X-1&_user=443835&_coverDate=07%2F31%2F2004&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000020958&_version=1&_urlVersion=0&_userid=443835&md5=525db1a96bf7be7620dabbcd34c426f9&search#toc2
10. Kubota, R., Noda, S., Wang, Y., Minoshima, S., Asakawa, S., Kudoh, J., Mashima, Y., Oguchi, Y., Shimizu, N. "A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping." Genomics. vol 41-3.1 May 1997, Pages 360-369 Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan. http://www.sciencedirect.com.ezproxy.library.wisc.edu/science?_ob=ArticleURL&_udi=B6WG1-45M8YTG-C5&_user=443835&_coverDate=05%2F01%2F1997&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000020958&_version=1&_urlVersion=0&_userid=443835&md5=1562ae0f98031b9d89c1c8377a859b1e&search
