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Human Molecular Genetics Advance Access originally published online on February 9, 2005
Human Molecular Genetics 2005 14(7):913-923; doi:10.1093/hmg/ddi084
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions{at}oupjournals.org

Natural antisense transcripts associated with genes involved in eye development

Giovanna Alfano1, Carmen Vitiello1, Cristina Caccioppoli1, Tiziana Caramico1, Antonietta Carola1, Michael J. Szego2, Roderick R. McInnes2,3, Alberto Auricchio1 and Sandro Banfi1,*

1Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy, 2Program in Genetics and Developmental Biology, Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto and 3Department of Pediatrics, University of Toronto, Toronto, Canada

* To whom correspondence should be addressed. Tel: +39 0816132200; Fax: +39 0815609877; Email: banfi{at}tigem.it

Received November 25, 2004; Revised January 11, 2005; Accepted February 3, 2005

Natural antisense transcripts (NATs) are a class of genes whose role in controlling gene expression is becoming more and more relevant. We describe the identification of eight novel mouse NATs associated with transcription factors (Pax6, Pax2, Six3, Six6, Otx2, Crx, Rax and Vax2) that play an important role in eye development and function. These newly identified NATs overlap with the mature processed mRNAs or with the primary unprocessed transcript of their corresponding sense genes, are predicted to represent either protein coding or non-coding RNAs and undergo extensive alternative splicing. Expression studies, by both RT–PCR and RNA in situ hybridization, demonstrate that most of these NATs, similarly to their sense counterparts, display a specific or predominant expression in the retina, particularly at postnatal stages. We found a significant reduction of the expression levels of one of these NATs, Vax2OS (Vax2 opposite strand) in a mouse mutant carrying the inactivation of Vax2, the corresponding sense gene. In addition, we overexpressed another NAT, CrxOS, in mouse adult retina using adeno-associated viral vectors and we observed a significant decrease in the expression levels of the corresponding sense gene, Crx. These results suggest that these transcripts are functionally related to their sense counterparts and may play an important role in regulating the molecular mechanisms that underlie eye development and function in both physiological and pathological conditions.


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