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PMID: 12485166 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A comparative cDNA microarray analysis reveals a spectrum of genes regulated by Pax6 in mouse lens.

Genes to cells : devoted to molecular & cellular mechanisms ·Vol. 7 ·No. 12 ·2002-12-00 ·Pages 1267-83

Chauhan BK, Reed NA, Yang Y, Cermák L, Reneker L, Duncan MK, Cvekl A

Abstract

Pax6 is a transcription factor that is required for induction, growth, and maintenance of the lens; however, few direct target genes of Pax6 are known. In this report, we describe the results of a cDNA microarray analysis of lens transcripts from transgenic mice over-expressing Pax6 in lens fibre cells in order to narrow the field of potential direct Pax6 target genes. This study revealed that the transcript levels were significantly altered for 508 of the 9700 genes analysed, including five genes encoding the cell adhesion molecules beta1-integrin, JAM1, L1 CAM, NCAM-140 and neogenin. Notably, comparisons between the genes differentially expressed in Pax6 heterozygous and Pax6 over-expressing lenses identified 13 common genes, including paralemmin, GDIbeta, ATF1, Hrp12 and Brg1. Immunohistochemistry and Western blotting demonstrated that Brg1 is expressed in the embryonic and neonatal (2-week-old) but not in 14-week adult lenses, and confirmed altered expression in transgenic lenses over-expressing Pax6. Furthermore, EMSA demonstrated that the BRG1 promoter contains Pax6 binding sites, further supporting the proposition that it is directly regulated by Pax6. These results provide a list of genes with possible roles in lens biology and cataracts that are directly or indirectly regulated by Pax6.

MeSH Terms
Animals Binding Sites Cell Adhesion Molecules/genetics,metabolism Cerebellum/physiology DNA Helicases Eye Proteins/genetics,metabolism Gene Expression Profiling Gene Expression Regulation Homeodomain Proteins/genetics,metabolism Humans Lens, Crystalline/cytology,physiology Mice Mice, Transgenic Molecular Sequence Data Nuclear Proteins/genetics,metabolism Oligonucleotide Array Sequence Analysis PAX6 Transcription Factor Paired Box Transcription Factors Promoter Regions, Genetic Repressor Proteins/genetics,metabolism Transcription Factors/genetics,metabolism
Chemicals
Cell Adhesion Molecules Eye Proteins Homeodomain Proteins Nuclear Proteins PAX6 Transcription Factor PAX6 protein, human Paired Box Transcription Factors Pax6 protein, mouse Repressor Proteins Transcription Factors SMARCA4 protein, human Smarca4 protein, mouse DNA Helicases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Chauhan Bharesh K
The Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Reed Nathan A
Yang Ying
Cermák Lukás
Reneker Lixing
Duncan Melinda K
Cvekl Ales
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Article Info
Journal
Genes to cells : devoted to molecular & cellular mechanisms
Abbr.
Genes Cells
ISSN
1356-9597
DOI
10.1046/j.1365-2443.2002.00602.x
Published
2002-12-00
Pages
1267-83
Language
English
Region
England
NLM ID
9607379
PMCID
PMC2080869
Subset
IM
Grants
NEI NIH HHS · R01 EY012221-04 · United States
NEI NIH HHS · R01 EY012200 · United States
NEI NIH HHS · R01 EY012200-03 · United States
NEI NIH HHS · EY12221 · United States
NEI NIH HHS · R01 EY012221 · United States
NEI NIH HHS · EY12200 · United States
NEI NIH HHS · R01 EY013146 · United States
NEI NIH HHS · EY13146 · United States
Databases
GENBANK
AC011442, AF254822
External Links
PubMed source DOI: 10.1046/j.1365-2443.2002.00602.x PMC Full Text View journal details
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