Abstract

This proposal is directed towards understanding how the human PAX6 gene and protein are regulated and identifying target genes regulated by PAX6.
The aims are 1) to identify the regulatory elements involved in PAX gene transcription; 2) to determine whether PAX6 regulates its own synthesis; 3)to use in vitro mutagenesis for studies of structure and function of the PAX6 protein; 4) to extend analyses of naturally occurring mutations in aniridia patients and examine the consequences of these mutations by constructing PAX6 expression vectors containing these mutations; and 5) to identify the target genes regulated by PAX6.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009675-05
Application #
2331654
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1992-08-01
Project End
2000-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Biochemistry
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Chao, Lian-Yu; Mishra, Rajnikant; Strong, Louise C et al. (2003) Missense mutations in the DNA-binding region and termination codon in PAX6. Hum Mutat 21:138-45
Xu, Zheng-Ping; Dutra, Amalia; Stellrecht, Christine M et al. (2002) Functional and structural characterization of the human gene BHLHB5, encoding a basic helix-loop-helix transcription factor. Genomics 80:311-8
Gorlov, Ivan P; Saunders, Grady F (2002) A method for isolating alternatively spliced isoforms: isolation of murine Pax6 isoforms. Anal Biochem 308:401-4
Mishra, Rajnikant; Gorlov, Ivan P; Chao, Lian Y et al. (2002) PAX6, paired domain influences sequence recognition by the homeodomain. J Biol Chem 277:49488-94
Singh, S; Chao, L Y; Mishra, R et al. (2001) Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function. Hum Mol Genet 10:911-8
Zheng, J B; Zhou, Y H; Maity, T et al. (2001) Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1. Nucleic Acids Res 29:4070-8
Singh, S; Stellrecht, C M; Tang, H K et al. (2000) Modulation of PAX6 homeodomain function by the paired domain. J Biol Chem 275:17306-13
Chao, L Y; Huff, V; Strong, L C et al. (2000) Mutation in the PAX6 gene in twenty patients with aniridia. Hum Mutat 15:332-9
Zhou, Y; Zheng, J B; Gu, X et al. (2000) A novel Pax-6 binding site in rodent B1 repetitive elements: coevolution between developmental regulation and repeated elements? Gene 245:319-28
Singh, S; Tang, H K; Lee, J Y et al. (1998) Truncation mutations in the transactivation region of PAX6 result in dominant-negative mutants. J Biol Chem 273:21531-41

Showing the most recent 10 out of 18 publications